REGISTER  |  SIGN IN
United States PatentRE39591
Or , ; et al.April 24, 2007
Title
6-O-substituted ketolides having antibacterial activity
Abstract
Antimicrobial compounds having the formula ##STR00001## as well as pharmaceutically acceptable salts, esters or prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds.
Inventors:Or; Yat Sun (Libertyville, IL), Ma; Zhenkun  (Gurnee, IL), Clark; Richard F.  (Mundelein, IL), Chu; Daniel T.  (Santa Clara, CA), Plattner; Jacob J.  (Berkeley, IL), Griesgraber; George  (Libertyville, IL)
Assignee:Abbott Laboratories (Abbott Park, IL)
Appl. No.:10/752,483
Filed:January 6, 2004
PCT Pub Date:May 2, 2007
Current U.S. Class:514/29 536/7.2 536/7.4 
Current International Class:A61K 31/70 (20060101) C07H 17/08 (20060101)
Field of Search:514/29 536/7.2,7.4
U.S. Patent Documents
5350839September 1994Asaka et al.
5444051August 1995Agouridas et al.
5527780June 1996Agouridas et al.
5561118October 1996Agouridas et al.
5770579June 1998Agouridas et al.
6274715August 2001Or et al.
Foreign Patent Documents
0 272 110Jun., 1988EP
0 638 585Nov., 1996EP
0487411May., 1992EP
0565364Jun., 1995EP
0596802May., 1994EP
0676409Oct., 1995EP
0680967Nov., 1995EP
2697524May., 1994FR
2738571Mar., 1997FR
WO 97/17356May., 1997WO
WO92/09614Jun., 1992WO
WO93/13116Jul., 1993WO
WO93/13663Jul., 1993WO
WO93/21199Oct., 1993WO
WO93/21200Oct., 1993WO
WO97/10251Mar., 1997WO
Other References
Pestka et al. (I), "Effect of Erythromycin Analogues on Binding of [.sup.14C]Erythromycin to Escherichia coli Ribosomes," Antimicrobial Agents and Chemotherapy, 6(4), 479-488 (Oct., 1974). cited by examiner .
Pestka et al. (II), "Correlation of Effects of Erythromycin Analogues on Intact Bacteria and on [.sup.14C]Erythromycin Binding to Escherichia coli Ribosomes," Antimicrobial Agents and Chemotherapy, 6(4), 488-491 (Oct., 1974). cited by examiner .
Pestka et al. (III), "Inhibition of [.sup.14C]Chloramphenicol Binding to Escherichia coli Ribosomes by Erythromycin Derivatives," Antimicrobial Agents and Chemotherapy, 6(1), 39-45 (Jul., 1974). cited by examiner .
Pestka et al. (IV), "Induction of Erythromycin Resistance in Staphylococcus aureus by Erythromycin Derivatives," Antimicrobial Agents and Chemotherapy, 9(1), 128-130 (Jan., 1976). cited by examiner .
LeMahieu et al., "Glycoside Cleavage Reactions on Erythromycin A. Preparation of Erythronolide A," Journal of Medicinal Chemistry, 17(9), 953-956 (Sep., 1974). cited by examiner.~
Primary Examiner: Jiang; S. Anna
Assistant Examiner: Crane; L. E.
Attorney, Agent or Firm:Wood, Phillips, Katz, Clark & Mortimer
Parent Case Text


This application is a continuation-in-part of U.S. application Ser. No. 08/707,776, filed Sep. 4, 1996 now abandoned.
Claims

What is claimed is:
1. A compound having the formula ##STR00058## or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein either, Y and Z taken together define a group X, wherein X is selected from the group consisting of (1) .dbd.O, (2) .dbd.N--OH, (3) .dbd.N--O--R.sup.1 where R.sup.1 is selected from the group consisting of (a) unsubstituted C.sub.1-C.sub.12-alkyl, (b) C.sub.1-C.sub.12-alkyl substituted with aryl, (c) C.sub.1-C.sub.12-alkyl substituted with substituted aryl, (d) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (e) C.sub.1-C.sub.12-alkyl substituted with substituted heteroaryl, (f) C.sub.3-C.sub.12-cycloalkyl, and (g) --Si--(R.sup.2)(R.sup.3)(R.sup.4) wherein R.sup.2, R.sup.3 and R.sup.4 are each independently selected from C.sub.1-C.sub.12-alkyl and Aryl; and (4) .dbd.N--O--C(R.sup.5)(R.sup.6)--O--R.sup.1 where R.sup.1 is as previously defined and R.sup.5 and R.sup.6 are each independently selected from the group consisting of (a) hydrogen, (b) unsubstituted C.sub.1-C.sub.12-alkyl, (c) C.sub.1-C.sub.12-alkyl substituted with aryl, (d) C.sub.1-C.sub.12-alkyl substituted with substituted aryl, (e) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, and (f) C.sub.1-C.sub.12-alkyl substituted with substituted heteroaryl, or R.sup.5 and R.sup.6 taken together with the atom to which they are attached form a C.sub.3-C.sub.12-cycloalkyl ring; or, one of Y and Z is hydrogen and the other is selected from a group consisting of (1) hydrogen, (2) hydroxy, (3) protected hydroxy, and (4) NR.sup.7R.sup.8 wherein R.sup.7 and R.sup.8 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.6-alkyl, or R.sup.7 and R.sup.8 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring which, when the ring is a 5- to 7-membered ring, may optionally contain a hetero function selected from the group consisting of --O--, --NH--, --N(C.sub.1-C.sub.6-alkyl-)-, --N(aryl)-, --N(aryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-aryl-C.sub.1-C.sub.6-alkyl-)-, --N(heteroaryl)-, --N(heteroaryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-heteroaryl-C.sub.1-C.sub.6-alkyl-)-, and --S-- or --S(O).sub.n--, wherein n is 1 or 2, R.sup.a is hydrogen or hydroxy; R.sup.b is selected from the group consisting of hydroxy, --O--C(O)--NH.sub.2 and --O--C(O)-imidazolyl; R.sup.c is hydrogen or a hydroxy protecting group; L is methylene or carbonyl, provided that when L is methylene, T is --O--, T is selected from the group consisting of --O--, --NH--, and --N(W--R.sup.d)--, wherein W is absent or is selected from the group consisting of --O--, --NH--CO--, --N.dbd.CH-- and --NH--; and R.sup.d is selected from the group consisting of (1) hydrogen, (2) C.sub.1-C.sub.6-alkyl optionally substituted with one or more substituents selected from the group consisting of (a) aryl, (b) substituted-aryl, (c) heteroaryl, (d) substituted-heteroaryl, (e) hydroxy, (f) C.sub.1-C.sub.6-alkoxy, (g) NR.sup.7R.sup.8, wherein R.sup.7 and R.sup.8 are as defined previously independently selected from the group consisting of hydrogen and C.sub.1-C.sub.6-alkyl, or R.sup.7 and R.sup.8 are taken with the nitrogen atom to which they are connected to form a 3 to 7 membered ring which, when the ring is a 5 to 7 membered ring, may optionally contain a hetero function selected from the group consisting of --O--, --NH--, --N(C.sub.1-C.sub.6-alkyl-), --N(aryl)-, --N(aryl C.sub.1-C.sub.6-alkyl-)-, --N(substituted aryl C.sub.1-C.sub.6-alkyl-)-, --N(heteroaryl)-, --N(heteroaryl C.sub.1-C.sub.6-alkyl-)-, --N(substituted heteroaryl C.sub.1-C.sub.6
alkyl-)-, --S-- and --S(O).sub.n-- where n is 1 or 2, and (h) --CH.sub.2--M--R.sup.9 wherein M is selected from the group consisting of: (i) --C(O)--NH--, (ii) --NH--C(O)--, (ii) --NH--, (iv) --N.dbd., (v) --N(CH.sub.3)--, (vi) --NH--C(O)--O-- (vii) --NH--C(O)--NH-- (viii) --O--C(O)--NH-- (ix) --O--C(O)--O-- (x) --O--, (xi) --S(O).sub.n--, wherein n is 0, 1 or 2, (xii) --C(O)--O--, (xiii) --O--C(O)--, and (xiv) --C(O)--, and R.sup.9 is selected from the group consisting of: (i) C.sub.1-C.sub.6-alkyl, optionally substituted with a substituent selected from the group consisting of (aa) aryl, (bb) substituted-aryl, (cc) heteroaryl, and (dd) substituted-heteroaryl, (ii) aryl, (iii) substituted-aryl, (iv) heteroaryl, (v) substituted-heteroaryl, and (vi) heterocycloalkyl, (3) C.sub.3-C.sub.7-cycloalkyl, (4) aryl, (5) substituted-aryl, (6) heteroaryl, and (7) substituted-heteroaryl; R is selected from the group consisting of (1) methyl substituted with a moiety selected from the group consisting of (a) CN, (b) F, (c) --CO.sub.2R.sup.10 wherein R.sup.10 is selected from the group consisting of C.sub.1-C.sub.3-alkyl or aryl substituted C.sub.1-C.sub.3-alkyl, or and heteroaryl substituted C.sub.1-C.sub.3-alkyl, (d) S(O).sub.nR.sup.10 where n is 0, 1 or 2 and R.sup.10 is as previously defined (e) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (f) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are independently selected from the group consisting of hydrogen, C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkyl substituted with aryl, substituted aryl, heteroaryl, and substituted heteroaryl, (g) aryl, (h) substituted aryl, (i) heteroaryl, and (j) substituted heteroaryl, (2) C.sub.2-C.sub.10-alkyl, (3) (2) C.sub.2-C.sub.10-alkyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxy, (c) C.sub.1-C.sub.3-alkoxy, (d) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkoxy, (e) oxo, (f) --N.sub.3, (g) --CHO, (h) O--SO.sub.2-(substituted C.sub.1-C.sub.6-alkyl), (i) --NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are selected from the group consisting of (i) hydrogen, (ii) C.sub.1-C.sub.12-alkyl, (iii) substituted C.sub.1-C.sub.12-alkyl, (iv) C.sub.1-C.sub.12-alkenyl, C.sub.2-C.sub.12-alkenyl, (v) substituted C.sub.1-C.sub.12-alkenyl, C.sub.2-C.sub.12-alkenyl, (vi) C.sub.1-C.sub.12-alkynyl, C.sub.2-C.sub.12-alkynyl, (vii) substituted C.sub.1-C.sub.12-alkynyl, C.sub.2-C.sub.12-alkynyl, (viii) aryl, (ix) C.sub.3-C.sub.8-cycloalkyl, (x) substituted C.sub.3-C.sub.8-cycloalkyl, (xi) substituted aryl, (xii) heterocycloalkyl, (xiii) substituted heterocycloalkyl, (xiv) C.sub.1-C.sub.12-substituted with aryl, (xv) C.sub.1-C.sub.12-substituted with substituted aryl, (xvi) C.sub.1-C.sub.12-alkyl substituted with heterocycloalkyl, (xvii) C.sub.1-C.sub.12-alkyl substituted with substituted heterocycloalkyl, (xviii) C.sub.1-C.sub.12-alkyl substituted with C.sub.3-C.sub.8-cycloalkyl, (xix) C.sub.1-C.sub.12-alkyl substituted with substituted C.sub.3-C.sub.8-cycloalkyl, (xx) heteroaryl, (xxi) substituted heteroaryl, (xxii) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, and (xxiii) C.sub.1-C.sub.12-alkyl substituted with substituted heteroaryl, or R.sup.13 and R.sup.14 are taken together with the atom to which they are attached form a 3-10 membered heterocycloalkyl ring which may be is optionally substituted with one or more substituents independently selected from the group consisting of (i) halogen, (ii) hydroxy, (iii) C.sub.1-C.sub.3-alkoxy, (iv) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkoxy, (v) oxo, (vi) C.sub.1-C.sub.3-alkyl, (vii) halo-C.sub.1-C.sub.3-alkyl, and (vii) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkyl, (j) --CO.sub.2R.sup.10 wherein R.sup.10 is as previously defined, (k) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (l) .dbd.N--O--R.sup.10 wherein R.sup.10 is as previously defined, (m) --C.ident.N, (n) O--S(O).sub.nR.sup.10 wherein n is 0, 1 or 2 and R.sup.10 is as (o) aryl, (p) substituted aryl, (q) heteroaryl, (r) substituted heteroaryl, (s) C.sub.3-C.sub.8-cycloalkyl, (t) substituted C.sub.3-C.sub.8-cycloalkyl, (u) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (v) heterocycloalkyl, (w) substituted heterocycloalkyl, (x) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (y) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (z) .dbd.N--NR.sup.13R.sup.14
wherein R.sup.13 and R.sup.14 are as previously defined, (aa) .dbd.N--R.sup.9 wherein R.sup.9 is as previously defined, (bb) .dbd.N--NHC(O)R.sup.10 wherein R.sup.10 is as previously defined, and (cc) .dbd.N--NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined; (4) (3) C.sub.3-alkenyl substituted with a moiety selected from the group consisting of (a) halogen, (b) --CHO, (c) --CO.sub.2R.sup.10 where R.sup.10 is as previously defined, (d) --C(O)--R.sup.9 where R.sup.9 is as previously defined, (e) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (f) --C.ident.N, (g) aryl, (h) substituted aryl, (i) heteroaryl, (j) substituted heteroaryl, (k) C.sub.3-C.sub.7-cycloalkyl, and (l) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (5) (4) C.sub.4-C.sub.10-alkenyl; (6) (5) C.sub.4-C.sub.10-alkenyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) C.sub.1-C.sub.3-alkoxy, (c) oxo, (d) --CHO, (e) --CO.sub.2R.sup.10 where R.sup.10 is as previously defined, (f) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (g) --NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (h) .dbd.N--O--R.sup.10 where R.sup.10 is as previously defined, (i) --C.ident.N, (j) O--S(O).sub.nR.sup.10 where n is 0, 1 or 2 and R.sup.10 is as previously defined, (k) aryl, (l) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) C.sub.3-C.sub.7-cycloalkyl, (p) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (q) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (r) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (s) .dbd.N--NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (t) .dbd.N--R.sup.9 wherein R.sup.9 is as previously defined, (u) .dbd.N--NHC(O)R.sup.10 where R.sup.10 is as previously defined, and (v) .dbd.N--NHC(O)NR.sup.11R.sup.12
wherein R.sup.11 and R.sup.12 are as previously defined; (7) (6) C.sub.3-C.sub.10-alkynyl; and (8) (7) C.sub.3-C.sub.10-alkynyl substituted with one or more substituents selected from the group consisting of (a) trialkylsilyl, (b) aryl, (c) substituted aryl, (d) heteroaryl, and (e) substituted heteroaryl. and A, B, D and E, with the provision that at least two of A, B, D and E are hydrogen, are independently selected from the group consisting of: (a) hydrogen; (b) C.sub.1-C.sub.6-alkyl, optionally substituted with one or more substituents selected from the group consisting of: (i) aryl; (ii) substituted-aryl; (iii) heteroaryl; (iv) substituted heteroaryl; (v) heterocycloalkyl; (vi) hydroxy; (vii) C.sub.1-C.sub.6-alkoxy; (viii) halogen consisting of Br, Cl, F or I; and (ix) NR.sup.7R.sup.8, wherein R.sup.7 and R.sup.8 are as previously defined; (c) C.sub.3-C.sub.7-cycloalkyl; (d) aryl; (e) substituted-aryl; (f) heteroaryl; (g) substituted-heteroaryl; (h) heterocycloalkyl; and (i) a group selected from option (b) above further substituted with --M--R.sup.9, wherein M and R.sup.9 are as previously defined; or any one pair of substituents, consisting of AB, AD, AE, BD, BE or DE, is taken together with the atom or atoms to which they are attached to form a 3- to 7-membered ring optionally containing a hetero function selected from the group consisting of --O--, --NH--, --N(C.sub.1-C.sub.6-alkyl-)-; --N(aryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-aryl-C.sub.1-C.sub.6-alkyl-)-, --N(heteroaryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-heteroaryl-C.sub.1-C.sub.6-alkyl-)-, --S-- or --S(O).sub.n--, wherein n is 1 or 2, --C(O)--NH--, --C(O)--NR.sup.12--, wherein R.sup.12 is as previously defined, --NH--C(O)--, --NR.sup.12--C(O)--, wherein R.sup.12 is as previously defined, and --C(.dbd.NH)--NH--.

2. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable carrier.

3. A method for controlling a bacterial infection in a mammal comprising administering to an mammal a therapeutically-effective pharmaceutical composition containing a compound according to claim 1.

4. A compound according to claim 1 which is selected from the group consisting of: Compound of Formula (III): Rc is acetyl, L is CO, T is NH, R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (III): R.sup.c is acetyl, L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (III): R.sup.c is benzoyl, L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (III): R.sup.c is propanoyl, L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); and Compound of Formula (III): R.sup.c is ethylsuccinoyl, L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-quinolyl).

5. A compound according to claim 1 having the formula (IX) ##STR00059## wherein L, T and R are as defined therein.

6. A compound according to claim 13claim 5which is selected from the group consisting of: Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-phenyl; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2CH.sub.2-Phenyl --CH.sub.2CH.sub.2CH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-chlorophenyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2CH.sub.3; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2NH.sub.2; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.NOH; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2CH.sub.2OH; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2F; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2-(4-pyridyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2-(4-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH (OH)CN; Compound of Formula (IX): L is CO, T is O, R is --CH(C(O)OCH.sub.3)CH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CN; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-methoxyphenyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-fluorophenyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(8-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2NHCH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2-(4-pyridyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2-(4-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-pyridyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2CH.sub.2-(4-pyridyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2CH.sub.2-(4-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(5-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2CH.sub.2-(5-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-benzoxazolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-benzimidazolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-Phenyl --CH.sub.2CH.dbd.CH-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.3; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NH.sub.2; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOH; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.2OH; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2F; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2-(4-pyridyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH(OH)CN; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2-(4-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH(C(O)OCH.sub.3)CH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CN; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-chlorophenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-fluorophenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.2-(4-methoxyphenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-methoxyphenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-chloro-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2-(2-chlorophenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2-(4-pyridyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2-(4-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-pyridyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.2-(4-pyridyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-fluoro-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.2-(4-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-cyano-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.2-(5-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-benzoxazolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-benzimidazolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-methoxy-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2-(2-naphthyl); Compound of Formula (IX): L is CO, T is N(CH.sub.3), R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is N(CH.sub.3), R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is N(CH.sub.2CH.sub.2N(CH.sub.3).sub.2), R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is N(CH.sub.2CH.sub.2N(CH.sub.3).sub.2), R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is N(CH.sub.2CH.dbd.CH.sub.2), R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is T is N(CH.sub.2CH.dbd.C-(3-quinolyl)), R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-pyridyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-isoquinolinyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3,4-ethylenedioxyphenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(8-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(5-indolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-chloro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3,4-ethylenedioxyphenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-nitrophenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-nitroquinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(5-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(2-methyl-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R.sup.c is acetyl; R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(5-isoquinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(7-nitro-6-quinoxalinyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-amino-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(1,8-naphthyridin-3-yl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-acetylamino)-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-carbazolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(5-benzimidazolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(-3-hydroxy-2-(N-(2-methoxyphenyl)amido)-7-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-quinoxalinyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-hydroxy-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-methoxy-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(5-nitro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(8-nitro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(2-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-carboxyl-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-fluoro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-methoxycarbonyl-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-aminocarbonyl-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-cyano-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-bromo-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2C(O)H; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2Phenyl --CH.sub.2CH.sub.2NHCH.sub.2phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2Phenyl --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2CH.sub.2Phenyl --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2CH.sub.2phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2CH.sub.2CH.sub.2Phenyl --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2CH.sub.2CH.sub.2phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2CH.sub.2-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2(6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NO(phenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2(phenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2(4-NO.sub.2-phenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2(4-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2(2-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2-(6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2-(1-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2-(2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHOCH.sub.2-(phenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHOCH.sub.2-(4-NO.sub.2-phenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2C(O)-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2C(O)-(4-F-phenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NNHC(O)phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.2-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2-(2-(3-quinolyl)cyclopropyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C--H; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(6-nitro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.dbd.C-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-naphthyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(6-methoxy-2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(6-chloro-2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(2-methyl-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(5-(N-(2-pyridyl)amino)carbonyl)furanyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(1-phenylethenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.dbd.C--Br; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2-(2,2-dimethyl-1,3-dioxolan-4-yl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH(OH)-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH(OH)CH.sub.2OH; Compound of Formula (IX): L is CO, T is NH NH.sub.2, R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is NH NH.sub.2, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH NH.sub.2, R is --CH.sub.2CH.sub.2CH.sub.2-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-naphthyl; Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(3-(2-firanyl)-6-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(8-chloro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(4-chloro-2-trifluoromethyl-6-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(9-fluorenone-2-yl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(6-benzoyl-2-naphthyl; Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(7-methoxy-2-naphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(3-phenyl-6-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(3-(2-pyridyl)-6-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(3-(2-thiophenyl)-6-quinolyl; Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(4-methylnaphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(6-.beta.-D-galactopyranosyl-2-naphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(7-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(4-fluoronaphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(3-biphenyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(5-nitronaphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(4-pyrrolylphenyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(6-methoxy-2-naphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(3,5-dichlorophenyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2-(3-iodophenyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2-(3-(2-furanyl)phenyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(6-hydroxy-2-naphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(6-(2-bromoethoxy)-2-naphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-(6-(2-(tetrazolyl)ethoxy-2-naphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2 , R is --CH.sub.2CH.dbd.CH-naphthyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(2-phenylethenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(5-(3-isoxazolyl)-2-thiophenyl); Compound of Formula (IX): L is CO, T is NH, R is
--CH.sub.2--CH.dbd.CH-(1,3-dimethyl-2,4-dioxo-5-pyrimidinyl); and Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--CH.dbd.CH-(5-(2-pyridyl)aminocarbonyl-2-furanyl).

7. A process for the preparation of 6-O-substituted macrolide compounds having the Formula: ##STR00060## wherein: R.sup.c is hydrogen or a hydroxy protecting group; L is carbonyl and T is --O--, and R is selected from the group consisting of (1) methyl substituted with a moiety selected from the group consisting of (a) CN, (b) F, (c) --CO.sub.2R.sup.10 wherein R.sup.10 is selected from the group consisting of C.sub.1-C.sub.3-alkyl or aryl substituted C.sub.1-C.sub.3-alkyl, or and heteroaryl substituted C.sub.1-C.sub.3-alkyl, (d) S(O).sub.nR.sup.10 where n is 0, 1 or 2 and R.sup.10 is as previously defined, (e) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (f) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are independently selected from the group consisting of hydrogen, C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkyl substituted with aryl, substituted aryl, heteroaryl, and substituted heteroaryl, (g) aryl, (h) substituted aryl, (i) heteroaryl, and (j) substituted heteroaryl, (2) C.sub.2-C.sub.10-alkyl, (3) (2) C.sub.2-C.sub.10-alkyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxy, (c) C.sub.1-C.sub.3-alkoxy, (d) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkoxy, (e) oxo, (f) --N.sub.3, (g) --CHO, (h) O--SO.sub.2-(substituted C.sub.1-C.sub.6-alkyl), (i) --NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are selected from the group consisting of (i) hydrogen, (ii) C.sub.1-C.sub.12-alkyl, (iii) substituted C.sub.1-C.sub.12-alkyl, (iv) C.sub.1 .sub.2-C.sub.12-alkenyl, (v) substituted C.sub.1 .sub.2-C.sub.12-alkenyl, (vi) C.sub.1 .sub.2-C.sub.12-alkynyl, (vii) substituted C.sub.1 .sub.2-C.sub.12-alkynyl, (viii) aryl, (ix) C.sub.3-C.sub.8-cycloalkyl, (x) substituted C.sub.3-C.sub.8-cycloalkyl, (xi) substituted aryl, (xii) heterocycloalkyl, (xiii) substituted heterocycloalkyl, (xiv) C.sub.1-C.sub.12-substituted with aryl, (xv) C.sub.1-C.sub.12-substituted with substituted aryl, (xvi) C.sub.1-C.sub.12-alkyl substituted with heterocycloalkyl, (xvii) C.sub.1-C.sub.12-alkyl substituted with substituted heterocycloalkyl, (xviii) C.sub.1-C.sub.12-alkyl substituted with C.sub.3-C.sub.8-cycloalkyl, (xix) C.sub.1-C.sub.12-alkyl substituted with substituted C.sub.3-C.sub.8-cycloalkyl, (xx) heteroaryl, (xxi) substituted heteroaryl, (xxii) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, and (xxiii) C.sub.1-C.sub.12-alkyl substituted with substituted heteroaryl, or R.sup.13 and R.sup.14
are taken together with the atom to which they are attached form a 3-10 membered heterocycloalkyl ring which may be is optionally substituted with one or more substituents independently selected from the group consisting of (i) halogen, (ii) hydroxy, (iii) C.sub.1-C.sub.3-alkoxy, (iv) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkoxy, (v) oxo, (vi) C.sub.1-C.sub.3-alkyl, (vii) halo-C.sub.1-C.sub.3-alkyl, and (vii) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkyl, (j) --CO.sub.2R.sup.10 wherein R.sup.10 is as previously defined, (k) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (l) .dbd.N--O--R.sup.10 wherein R.sup.10 is as previously defined, (m) --C.ident.N, (n) O--S(O).sub.nR.sup.10 wherein n is 0, 1 or 2 and R.sup.10 is as previously defined, (o) aryl, (p) substituted aryl, (q) heteroaryl, (r) substituted heteroaryl, (s) C.sub.3-C.sub.8-cycloalkyl, (t) substituted C.sub.3-C.sub.8-cycloalkyl, (u) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (v) heterocycloalkyl, (w) substituted heterocycloalkyl, (x) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (y) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (z) .dbd.N--NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (aa) .dbd.N--R.sup.9 wherein R.sup.9 is as previously defined, (bb) .dbd.N--NHC(O)R.sup.10 wherein R.sup.10 is as previously defined, and (cc) .dbd.N--NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined; (4) (3) C.sub.3-alkenyl substituted with a moiety selected from the group consisting of (a) halogen, (b) --CHO, (c) --CO.sub.2R.sup.10 where R.sup.10 is as previously defined, (d) --C(O)--R.sup.9 where R.sup.9 is as previously defined, (e) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (f) --C.ident.N, (g) aryl, (h) substituted aryl, (i) heteroaryl, (j) substituted heteroaryl, (k) C.sub.3-C.sub.7-cycloalkyl, and (l) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (5) (4) C.sub.4-C.sub.10-alkenyl; (6) (5) C.sub.4-C.sub.10-alkenyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) C.sub.1-C.sub.3-alkoxy, (c) oxo, (d) --CHO, (e) --CO.sub.2R.sup.10 where R.sup.10 is as previously defined, (f) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (g) --NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (h) .dbd.N--O--R.sup.10 where R.sup.10 is as previously defined, (i) --C.ident.N, (j) O--S(O).sub.nR.sup.10 where n is 0, 1 or 2 and R.sup.10 is as previously defined, (k) aryl, (l) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) C.sub.3-C.sub.7-cycloalkyl, (p) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (q) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (r) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (s) .dbd.N--NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (t) .dbd.N--R.sup.9 wherein R.sup.9 is as previously defined, (u) .dbd.N--NHC(O)R.sup.10 where R.sup.10 is as previously defined, and (v) .dbd.N--NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined; (7) (6) C.sub.3-C.sub.10-alkynyl; and (8) (7) C.sub.3-C.sub.10-alkynyl substituted with one or more substituents selected from the group consisting of (a) trialkylsilyl, (b) aryl, (c) substituted aryl, (d) heteroaryl, and (e) substituted heteroaryl; the method comprising: treating a compound having the formula ##STR00061## wherein R is as defined previously and R.sup.c is a hydroxy protecting group, with carbonyldiimidazole and sodium hexamethyldisilazide to give make the desired compound wherein R.sup.c is a hydroxy protecting group, optionally deprotecting, and isolating the desired compound of the formula ##STR00062## wherein R, R.sup.c, L and T are as previously defined.

8. A process for the preparation of 6-O-substituted macrolide compounds having the Formula: ##STR00063## wherein: R.sup.c is hydrogen or a hydroxy protecting group; L is carbonyl, T is selected from the group consisting of --NH--, and --N(W--R.sup.d)--, wherein W is absent or is selected from the group consisting of --O--, --NH--CO--, --N.dbd.CH-- and --NH--; and R.sup.d is selected from the group consisting of (1) hydrogen, (2) C.sub.1-C.sub.6-alkyl optionally substituted with one or more substituents selected from the group consisting of (a) aryl, (b) substituted-aryl, (c) heteroaryl, (d) substituted-heteroaryl, (e) hydroxy, (f) C.sub.1-C.sub.6-alkoxy, (g) NR.sup.7R.sup.8, wherein R.sup.7 and R.sup.8 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.6-alkyl, or R.sup.7 and R.sup.8 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring which, when the ring is a 5- to 7-membered ring, may optionally contain a hetero function selected from the group consisting of --O--, --NH--, --N(C.sub.1-C.sub.6-alkyl-)-, --N(aryl)-, --N(aryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-aryl-C.sub.1-C.sub.6-alkyl-)-, --N(heteroaryl)-, --N(heteroaryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-heteroaryl-C.sub.1-C.sub.6-alkyl-)-, and --S-- or and --S(O).sub.n--, wherein n is 1 or 2, and (h) --CH.sub.2--M--R.sup.9 wherein M is selected from the group consisting of: (i) --C(O)--NH--, (ii) --NH--C(O)--, (ii) --NH--, (iv) --N.dbd., (v) --N(CH.sub.3)--, (vi) --NH--C(O)--O-- (vii) --NH--C(O)--NH-- (viii) --O--C(O)--NH-- (ix) --O--C(O)--O-- (x) --O--, (xi) --S(O).sub.n--, wherein n is 0, 1 or 2, (xii) --C(O)--O--, (xiii) --O--C(O)--, and (xiv) --C(O)--, and R.sup.9 is selected from the group consisting of: (i) C.sub.1-C.sub.6-alkyl, optionally substituted with a substituent selected from the group consisting of (aa) aryl, (bb) substituted-aryl, (cc) heteroaryl, and (dd) substituted-heteroaryl, (ii) aryl, (iii) substituted-aryl, (iv) heteroaryl, (v) substituted-heteroaryl, and (vi) heterocycloalkyl, (3) C.sub.3-C.sub.7-cycloalkyl, (4) aryl, (5) substituted-aryl, (6) heteroaryl, and (7) substituted-heteroaryl; and R is selected from the group consisting of (1) methyl substituted with a moiety selected from the group consisting of (a) CN, (b) F, (c) --CO.sub.2R.sup.10 wherein R.sup.10 is selected from the group consisting of C.sub.1-C.sub.3-alkyl or aryl substituted C.sub.1-C.sub.3-alkyl, or and heteroaryl substituted C.sub.1-C.sub.3-alkyl, (d) S(O).sub.nR.sup.10 where n is 0, 1 or 2 and R.sup.10 is as previously defined, (e) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (f) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are independently selected from the group consisting of hydrogen, C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkyl substituted with aryl, substituted aryl, heteroaryl, and substituted heteroaryl, (g) aryl, (h) substituted aryl, (i) heteroaryl, (j) substituted heteroaryl, (2) C.sub.2-C.sub.10-alkyl, (3) (2) C.sub.2-C.sub.10-alkyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxy, (c) C.sub.1-C.sub.3-alkoxy, (d) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkoxy, (e) oxo, (f) --N.sub.3, (g) --CHO, (h) O--SO.sub.2-(substituted C.sub.1-C.sub.6-alkyl), (i) --NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are selected from the group consisting of (i) hydrogen, (ii) C.sub.1-C.sub.12-alkyl, (iii) substituted C.sub.1-C.sub.12-alkyl, (iv) C.sub.1 .sub.2-C.sub.12-alkenyl, (v) substituted C.sub.1 .sub.2-C.sub.12-alkenyl, (vi) C.sub.1 .sub.2-C.sub.12-alkynyl, (vii) substituted C.sub.1 .sub.2-C.sub.12-alkynyl, (viii) aryl, (ix) C.sub.3-C.sub.8-cycloalkyl, (x) substituted C.sub.3-C.sub.8-cycloalkyl, (xi) substituted aryl, (xii) heterocycloalkyl, (xiii) substituted heterocycloalkyl, (xiv) C.sub.1-C.sub.12-alkyl substituted with aryl, (xv) C.sub.1-C.sub.12-alkyl substituted with substituted aryl, (xvi) C.sub.1-C.sub.12-alkyl substituted with heterocycloalkyl, (xvii) C.sub.1-C.sub.12-alkyl substituted with substituted heterocycloalkyl, (xviii) C.sub.1-C.sub.12-alkyl substituted with C.sub.3-C.sub.8-cycloalkyl, (xix) C.sub.1-C.sub.12-alkyl substituted with substituted C.sub.3-C.sub.8-cycloalkyl, (xx) heteroaryl, (xxi) substituted heteroaryl, (xxii) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, and (xxiii) C.sub.1-C.sub.12-alkyl substituted with substituted heteroaryl, or R.sup.13 and R.sup.14
are taken together with the atom to which they are attached form a 3-10 membered heterocycloalkyl ring which may be is optionally substituted with one or more substituents independently selected from the group consisting of (i) halogen, (ii) hydroxy, (iii) C.sub.1-C.sub.3-alkoxy, (iv) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkoxy, (v) oxo, (vi) C.sub.1-C.sub.3-alkyl, (vii) halo-C.sub.1-C.sub.3-alkyl, and (vii) (viii) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkyl, (j) --C.sub.O O.sub.2R.sup.10 wherein R.sup.10 is as previously defined, (k) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (l) .dbd.N--O--R.sup.10 wherein R.sup.10 is as previously defined, (m) --C.ident.N, (n) O--S(O).sub.nR.sup.10 wherein n is 0, 1 or 2
and R.sup.10 is as previously defined, (o) aryl, (p) substituted aryl, (q) heteroaryl, (r) substituted heteroaryl, (s) C.sub.3-C.sub.8-cycloalkyl, (t) substituted C.sub.3-C.sub.8-cycloalkyl, (u) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (v) heterocycloalkyl, (w) substituted heterocycloalkyl, (x) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (y) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (z) .dbd.N--NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (aa) .dbd.N--R.sup.9 wherein R.sup.9 is as previously defined, (bb) .dbd.N--NHC(O)R.sup.10 wherein R.sup.10 is as previously defined, and (cc) .dbd.N--NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined; (4) (3) C.sub.3-alkenyl substituted with a moiety selected from the group consisting of (a) halogen, (b) --CHO, (c) --CO.sub.2R.sup.10 where R.sup.10 is as previously defined, (d) --C(O)--R.sup.9 where R.sup.9 is as previously defined, (e) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (f) --C.ident.N, (g) aryl, (h) substituted aryl, (i) heteroaryl, (j) substituted heteroaryl, (k) C.sub.3-C.sub.7-cycloalkyl, and (l) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (5) (4) C.sub.4-C.sub.10-alkenyl; (6) (5) C.sub.4-C.sub.10-alkenyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) C.sub.1-C.sub.3-alkoxy, (c) oxo, (d) --CHO, (e) --CO.sub.2R.sup.10 where R.sup.10 is as previously defined, (f) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (g) --NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (h) .dbd.N--O--R.sup.10
where R.sup.10 is as previously defined, (i) --C.ident.N, (j) O--S(O).sub.nR.sup.10 where n is 0, 1 or 2 and R.sup.10 is as previously defined, (k) aryl, (l) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) C.sub.3-C.sub.7-cycloalkyl, (p) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (q) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (r) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (s) .dbd.N--NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (t) .dbd.N--R.sup.9 wherein R.sup.9 is as previously defined, (u) .dbd.N--NHC(O)R.sup.10 where R.sup.10 is as previously defined, and (v) .dbd.N--NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined; (7) (6) C.sub.3-C.sub.10-alkynyl; and (8) (7) C.sub.3-C.sub.10-alkynyl substituted with one or more substituents selected from the group consisting of (a) trialkylsilyl, (b) aryl, (c) substituted aryl, (d) heteroaryl, and (e) substituted heteroaryl; the method comprising: (a) treating a compound having the formula ##STR00064## wherein R is as defined previously, and R.sup.c R.sup.p is a hydroxy protecting group, by treatment treating with sodium hexamethyldisilazide and carbonyldiimidazole to give make a compound having the formula ##STR00065## (b) (1) treating the compound from step (a) with a reagent selected from the group consisting of ammonia, R.sup.e--NH.sub.2, hydrazine, substituted hydrazine, hydroxylamine, and substituted hydroxylamine to give make a compound having the formula ##STR00066## wherein R.sup.e is H or W--R.sup.d, wherein W is absent or is selected from the group consisting of --O--, --NH--CO--, --N.dbd.CH-- and --NH--, and R.sup.d is as defined previously, (c) optionally treating the compound from step (b) wherein W is absent or is --NH-- with an alkylating agent selected from the group consisting of of the formula R.sup.d-halogen to give make a compound wherein W is absent or is --NH-- and R.sup.d is as defined above; (d) optionally treating the compound from step (b) wherein W is --NH-- and R.sup.d is H with an acylating agent selected from the group consisting of R.sup.d--C(C O)-halogen or and (R.sup.d--C(C O)).sub.2-- O).sub.2 --to give make a compound wherein W is --NH--CO-- and R.sup.d is as defined above; (e) optionally treating the compound from step (b) wherein W is --NH-- and R.sup.d is H with an aldehyde R.sup.d--CHO, wherein R.sup.d as defined above to give make a compound wherein W is --N.dbd.CH-- and R.sup.d is as defined above; and (f) optionally deprotecting, and isolating the desired compound of the formula ##STR00067## wherein R, R.sup.c, L and T are as previously defined.

9. A process for preparing a compound having the formula ##STR00068## wherein R and R.sup.p R is selected from the group consisting of (1) methyl substituted with a moiety selected from the group consisting of (a) CN, (b) F, (c) --CO.sub.2R.sup.10 wherein R.sup.10 is selected from the group consisting of C.sub.1-C.sub.3-alkyl or aryl substituted C.sub.1-C.sub.3-alkyl, or and heteroaryl substituted C.sub.1-C.sub.3-alkyl, (d) S(O).sub.nR.sup.10 where n is 0, 1 or 2 and R.sup.10 is as previously defined, (e) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (f) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are independently selected from the group consisting of hydrogen, C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkyl substituted with aryl, substituted aryl, heteroaryl, and substituted heteroaryl, (g) aryl, (h) substituted aryl, (i) heteroaryl, and (j) substituted heteroaryl, (2) C.sub.2-C.sub.10-alkyl, (3) (2) C.sub.2-C.sub.10-alkyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxy, (c) C.sub.1-C.sub.3-alkoxy, (d) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkoxy, (e) oxo, (f) --N.sub.3, (g) --CHO, (h) O--SO.sub.2-(substituted C.sub.1-C.sub.6-alkyl), (i) --NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are selected from the group consisting of (i) hydrogen, (ii) C.sub.1-C.sub.12-alkyl, (iii) substituted C.sub.1-C.sub.12-alkyl, (iv) C.sub.1 .sub.2-C.sub.12-alkenyl, (v) substituted C.sub.1
.sub.2-C.sub.12-alkenyl, (vi) C.sub.1 .sub.2-C.sub.12-alkynyl, (vii) substituted C.sub.1 .sub.2-C.sub.12-alkynyl, (viii) aryl, (ix) C.sub.3-C.sub.8-cycloalkyl, (x) substituted C.sub.3-C.sub.8-cycloalkyl, (xi) substituted aryl, (xii) heterocycloalkyl, (xiii) substituted heterocycloalkyl, (xiv) C.sub.1-C.sub.12-alkyl substituted with aryl, (xv) C.sub.1-C.sub.12-alkyl substituted with substituted aryl, (xvi) C.sub.1-C.sub.12-alkyl substituted with heterocycloalkyl, (xvii) C.sub.1-C.sub.12-alkyl substituted with substituted heterocycloalkyl, (xviii) C.sub.1-C.sub.12-alkyl substituted with C.sub.3-C.sub.8-cycloalkyl, (xix) C.sub.1-C.sub.12-alkyl substituted with substituted C.sub.3-C.sub.8-cycloalkyl, (xx) heteroaryl, (xxi) substituted heteroaryl, (xxii) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, and (xxiii) C.sub.1-C.sub.12-alkyl substituted with substituted heteroaryl, or R.sup.13 and R.sup.14 are taken together with the atom to which they are attached form a 3-10 membered heterocycloalkyl ring which may be is optionally substituted with one or more substituents independently selected from the group consisting of (i) halogen, (ii) hydroxy, (iii) C.sub.1-C.sub.3-alkoxy, (iv) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkoxy, (v) oxo, (vi) C.sub.1-C.sub.3-alkyl, (vii) halo-C.sub.1-C.sub.3-alkyl, and (vii) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkyl, (j) --CO.sub.2R.sup.10 wherein R.sup.10 is as previously defined, (k) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (l) .dbd.N--O--R.sup.10 wherein R.sup.10 is as previously defined, (m) --C.ident.N, (n) O--S(O).sub.nR.sup.10 wherein n is 0, 1 or 2 and R.sup.10 is as previously defined, (o) aryl, (p) substituted aryl, (q) heteroaryl, (r) substituted heteroaryl, (s) C.sub.3-C.sub.8-cycloalkyl, (t) substituted C.sub.3-C.sub.8-cycloalkyl, (u) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (v) heterocycloalkyl, (w) substituted heterocycloalkyl, (x) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (y) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (z) .dbd.N--NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (aa) .dbd.N--R.sup.9 wherein R.sup.9 is as previously defined, (bb) .dbd.N--NHC(O)R.sup.10 wherein R.sup.10 is as previously defined, and (cc) .dbd.N--NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined; (4) (3) C.sub.3-alkenyl substituted with a moiety selected from the group consisting of (a) halogen, (b) --CHO, (c) --CO.sub.2R.sup.10 where R.sup.10 is as previously defined, (d) --C(O)--R.sup.9 where R.sup.9 is as previously defined, (e) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (f) --C.ident.N, (g) aryl, (h) substituted aryl, (i) heteroaryl, (j) substituted heteroaryl, (k) C.sub.3-C.sub.7-cycloalkyl, and (l) C.sub.1-C.sub.2-alkyl substituted with heteroaryl, (5) (4) C.sub.4-C.sub.10-alkenyl; (6) (5) C.sub.4-C.sub.10-alkenyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) C.sub.1-C.sub.3-alkoxy, (c) oxo, (d) --CHO, (e) --CO.sub.2R.sup.10 where R.sup.10 is as previously defined, (f) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (g) --NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (h) .dbd.N--O--R.sup.10 where R.sup.10 is as previously defined, (i) --C.ident.N, (j) O--S(O).sub.nR.sup.10 where n is 0, 1 or 2 and R.sup.10 is as previously defined, (k) aryl, (l) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) C.sub.3-C.sub.7-cycloalkyl, (p) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (q) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (r) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (s) .dbd.N--NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (t) .dbd.N--R.sup.9 wherein R.sup.9 is as previously defined, (u) .dbd.N--NHC(O)R.sup.10 where R.sup.10 is as previously defined, and (v) .dbd.N--NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined; (7) (6) C.sub.3-C.sub.10-alkynyl; and (8) (7) C.sub.3-C.sub.10-alkynyl substituted with one or more substituents selected from the group consisting of (a) trialkylsilyl, (b) aryl, (c) substituted aryl, (d) heteroaryl, and (e) substituted heteroaryl; R.sup.e is H or W--R.sup.d, wherein W is absent or is selected from the group consisting of --O--, --NH--CO--, 13 N.dbd.CH-- and --NH--, and R.sup.d is selected from the group consisting of (1) hydrogen, (2) C.sub.1-C.sub.6-alkyl optionally substituted with one or more substituents selected from the group consisting of (a) aryl, (b) substituted-aryl, (c) heteroaryl, (d) substituted-heteroaryl, (e) hydroxy, (f) C.sub.1-C.sub.6-alkoxy, (g) NR.sup.7R.sup.8, wherein R.sup.7 and R.sup.8 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.6-alkyl, or R.sup.7
and R.sup.8 are taken with the nitrogen atom to which they are connected to form a 3- or 7-membered ring which, when the ring is a 5- to 7-membered ring, may optionally contain a hetero function selected from the group consisting of --O--, --NH--, --N(C.sub.1-C.sub.6-alkyl-)-, --N(aryl)-, --N(aryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-aryl-C.sub.1-C.sub.6-alkyl-)-, --N(heteroaryl)-, --N(heteroaryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-heteroaryl-C.sub.1-C.sub.6-alkyl-)-, and --S-- or and --S(O).sub.n--, wherein n is 1 or 2, and (h) --CH.sub.2--M--R.sup.9 wherein M is selected from the group consisting of: (i) --C(O)--NH--, (ii) --NH--C(O)--, (iii) --NH--, (iv) --N.dbd., (v) --N(CH.sub.3)--, (vi) --NH--C(O)--O-- (vii) --NH--C(O)--NH-- (viii) --O--C(O)--NH-- (ix) --O--C(O)--O-- (x) --O--, (xi) --S(O).sub.n--, wherein n is 0, 1 or 2, (xii) --C(O)--O--, (xiii) --O--C(O)--, and (xiv) --C(O)--, and R.sup.9 is selected from the group consisting of: (i) C.sub.1-C.sub.6-alkyl, optionally substituted with a substituent selected from the group consisting of (aa) aryl, (bb) substituted-aryl, (cc) heteroaryl, and (dd) substituted-heteroaryl, (ii) aryl, (iii) substituted-aryl, (iv) heteroaryl, (v) substituted-heteroaryl, and (vi) heterocycloalkyl, (3) C.sub.3-C.sub.7-cycloalkyl, (4) aryl, (5) substituted-aryl, (6) heteroaryl, and (7) substituted-heteroaryl; and R.sup.p is a hydroxy protecting group; the method comprising (a) treating a compound having the formula ##STR00069## wherein R is and R.sup.p are as previously defined, R.sup.p is a hydroxy protecting group and Z' is 4''-hydroxy-protected cladinose, with sodium hexamethyldisilazide and carbonyldiimidazole to give make a compound having the formula ##STR00070## (b) treating the compound from step (a) with a reagent selected from the group consisting of ammonia, R.sup.c--NH.sub.2, hydrazine, substituted hydrazine, hydroxylamine, and substituted hydroxylamine to give make a compound having the formula ##STR00071## wherein R.sup.e is H or W--R.sup.d, wherein W is absent or is selected from the group consisting of --O--, --NH--CO--, --N.dbd.CH-- and --NH--, and R.sup.d is as defined previously, (c) optionally treating the compound from step (b) wherein R.sup.c is H with an alkylating agent having the formula R.sup.d-halogen, wherein R.sup.d is as defined previously, to give make a compound of the formula shown in of step (b) wherein R.sup.e is W--R.sup.d, W is absent and R.sup.d is as defined previously; (d) optionally treating the compound from step (b) wherein R.sup.e is W--R.sup.d and W is --NH-- and R.sup.d is H, with an alkylating agent selected from the group consisting of R.sup.d-halogen, wherein R.sup.d is as defined previously, to give make a compound of the formula shown in step (b) wherein R.sup.e is W--R.sup.d, W is --NH-- and R.sup.d is as defined above; (e) optionally treating the compound from step (b) wherein R.sup.e is W--R.sup.d and W is --NH-- and R.sup.d is H, with an alkylating agent selected from the group consisting of R.sup.d--C(C O)-- halogen or and (R.sup.d--C(C O))-- .sub.2 O).sub.2 to give make a compound wherein R.sup.e is W--R.sup.d, W is --NH--CO-- and R.sup.d is as defined above; (f) optionally treating the compound from step (b) wherein R.sup.e is W--R.sup.d and W is --NH-- and R.sup.d is H, with an aldehyde having the formula R.sup.d--CHO, wherein R.sup.d as defined above to give make a compound wherein R.sup.e is W--R.sup.d, W is --N.dbd.CH-- and R.sup.d is as defined above; (g) removing the cladinose moiety by hydrolysis with acid to give make a compound having the formula ##STR00072## (h) oxidizing the 3-hydroxyl group; and (i) optionally deprotecting, and isolating the desired compound of the formula ##STR00073## where R, R.sup.e and R.sup.p are as defined above.

10. A process according to claim 9 wherein R is selected from the group consisting of allyl and propargyl, wherein the allyl or propargyl moiety is further substituted with a moiety selected from the group consisting of 2-chlorophenyl,
2-fluorenyl, 2-methyl-6-quinolyl, 2-naphthyl, 2-phenylethenyl, 2-quinolyl, 3-(2-furanyl)-6-quinolyl, 3-(2-pyridyl)-6-quinolyl, 3-quinolyl, 3-(2-thiophenyl)-6-quinolyl, 3-biphenyl, 3-bromo-6-quinolyl, 3-carbazolyl, 3-chloro-6-quinolyl, 3-cyano-6-quinolyl,
3-fluoro-6-quinolyl, 3-hydroxy-2-(N-(2-methoxyphenyl)amido)-7-naphthyl, 3-iodophenyl, 3-methoxy-6-quinolyl, 3-nitrophenyl, 3-phenyl-6-quinolyl, 3-quinolyl, 4-benzoxazolyl, 4-carboxyl-3-quinolyl, 4-chloro-2-trifluoromethyl-6-quinolyl, 4-chlorophenyl,
4-fluoronaphthyl, 4-fluorophenyl, 4-isoquinolinyl, 4-methoxyphenyl, 4-methylnaphthyl, 4-pyridyl, 4-pyrrolylphenyl, 4-quinolyl, 5-(2-pyridyl)aminocarbonyl-2-furanyl, 5-(3-isoxazolyl)-2-thiophenyl, 5-benzimidazolyl, 5-indolyl, 5-isoquinolyl,
5-nitro-3-quinolyl, 5-nitronaphthyl, 5-quinolyl, 6-(acetylamino)-3-quinolyl, 6-(2-(tetrazolyl)ethoxy-2-naphthyl, 6-(2-bromoethoxy)-2-naphthyl, 6-amino-3-quinolyl, 6-aminocarbonyl-3-quinolyl, 6-.beta.-D-galactopyranosyl-2-15 naphthyl,
6-benzoyl-2-naphthyl, 6-cyano-3-quinolyl, 6-fluoro-3-quinolyl, 6-hydroxy-2-naphthyl, 6-hydroxy-3-quinolyl, 6-methoxy-2-naphthyl, 6-methoxy-3-quinolyl, 6-methoxycarbonyl-3-quinolyl, 6-nitroquinolyl, 6-quinolyl, 6-quinoxalinyl, 7-methoxy-2-naphthyl,
7-nitro-6-quinoxalinyl, 7-quinolyl, 8-chloro-3-quinolyl, 8-nitro-3-quinolyl, 8-quinolyl, 9-oxofluoren-2-yl, 1,3-dimethyl-2,4-dioxo-5-pyrimidinyl, 1,8-naphthyridin-3-yl, 3,4-methylenedioxyphenyl, 3,5-dichlorophenyl, naphthyl, and phenyl, and in step (b) the reagent is selected from the group consisting of ammonia and R.sup.e--NH.sub.2; optional steps (c), (d) and (e) are omitted; and in step (g) the oxidizing reagent is selected from N-chlorosuccinimide-dimethyl sulfide and carbodiimide-dimethylsulfoxide; and in step (h) the optional deprotection is carried out by stirring in methanol.

11. A process according to claim 10 wherein R is selected from the group consisting of allyl and propargyl, wherein the allyl or propargyl moiety is further substituted with a moiety selected from the group consisting of 2-methyl-6-quinolyl,
2-quinolyl, 3-(2-furanyl)-6-quinolyl, 3-(2-pyridyl)-6-quinolyl, 3-quinolyl, 3-(2-thiophenyl)-6-quinolyl, 3-bromo-6-quinolyl, 3-chloro-6-quinolyl, 3-cyano-6-quinolyl, 3-fluoro-6-quinolyl, 3-methoxy-6-quinolyl, 3-phenyl-6-quinolyl, 3-quinolyl,
4-carboxyl-3-quinolyl, 4-chloro-2-trifluoromethyl-6-quinolyl, 4-isoquinolinyl, 4-quinolyl, 5- isoquinolyl, 5-nitro-3-quinolyl, 5-quinolyl, 6-(acetylamino)-3-quinolyl, 6-amino-3-quinolyl, 6-aminocarbonyl-3-quinolyl, 6-cyano-3-quinolyl,
6-fluoro-3-quinolyl, 6-hydroxy-3-quinolyl, 6-methoxy-3-quinolyl, 6-methoxycarbonyl-3-quinolyl, 6-nitroquinolyl, 6-quinolyl, 7-quinolyl, 8-chloro-3-quinolyl, 8-nitro-3-quinolyl and 8-quinolyl.

12. A process for preparing a compound having the formula ##STR00074## wherein R.sup.e is H or W--R.sup.d, wherein W is absent or is selected from the group consisting of --O--, --NH--CO--, --N.dbd.CH-- and --NH--, and R.sup.d is selected from the group consisting of (1) hydrogen, (2) C.sub.1-C.sub.6-alkyl optionally substituted with one or more substituents selected from the group consisting of (a) aryl, (b) substituted-aryl, (c) heteroaryl, (d) substituted-heteroaryl, (e) hydroxy, (f) C.sub.1-C.sub.6-alkoxy, (g) NR.sup.7R.sup.8 wherein R.sup.7 and R.sup.8 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.6-alkyl, or R.sup.7 and R.sup.8 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring which, when the ring is a 5- to 7-membered ring, may optionally contain a hetero function selected from the group consisting of --O--, --NH--, --N(C.sub.1-C.sub.6-alkyl-)-, --N(aryl)-, --N(aryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-aryl-C.sub.1-C.sub.6-alkyl-)-, --N(heteroaryl)-, --N(heteroaryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-heteroaryl-C.sub.1-C.sub.6-alkyl-)-, and --S--or and --S(O).sub.n--, wherein n is 1 or 2, and (h) --CH.sub.2--M--R.sup.9 wherein M is selected from the group consisting of: (i) --C(O)--NH--, (ii) --NH--C(O)--, (iii) --NH--, (iv) --N.dbd., (v) --N(CH.sub.3)--, (vi) --NH--C(O)--O-- (vii) --NH--C(O)--NH-- (viii) --O--C(O)--NH-- (ix) --O--C(O)--O-- (x) --O--, (xi) --S(O).sub.n--, wherein n is 0, 1 or 2, (xii) --C(O)--O--, (xiii) --O--C(O)--, and (xiv) --C(O)--, and R.sup.9 is selected from the group consisting of: (i) C.sub.1-C.sub.6-alkyl, optionally substituted with a substituent selected from the group consisting of (aa) aryl, (bb) substituted-aryl, (cc) heteroaryl, and (dd) substituted-heteroaryl, (ii) aryl, (iii) substituted-aryl, (iv) heteroaryl, (v) substituted-heteroaryl, and (vi) heterocycloalkyl, (3) C.sub.3-C.sub.7-cycloalkyl, (4) aryl, (5) substituted-aryl, (6) heteroaryl, and (7) substituted-heteroaryl; and R.sup.10 is selected from the group consisting of H or , C.sub.1-C.sub.3-alkyl, aryl substituted C.sub.1-C.sub.3-alkyl, or and heteroaryl substituted C.sub.1-C.sub.3-alkyl, and R.sup.p is a hydroxyl protecting group, the method comprising (a) treating a compound having the formula ##STR00075## with ozone to give make a compound having the formula ##STR00076## (b) treating the resultant compound of step (a) with a hydroxylamine compound having the formula NH.sub.2--O--R.sup.10, wherein R.sup.10 is as previously defined; and (c) optionally deprotecting, and isolating the desired compound of the formula ##STR00077## where R.sup.e, R.sup.p and R.sup.10 are as previously defined.

13. A process according to claim 12 wherein R.sup.e is H.

14. A process for preparing a compound having the formula ##STR00078## wherein R.sup.e is H or W--R.sup.d, wherein W is absent or is selected from the group consisting of --O--, --NH--CO--, --N.dbd.CH-- and --NH--, and R.sup.d is selected from the group consisting of (1) hydrogen, (2) C.sub.1-C.sub.6-alkyl optionally substituted one or more substituents selected from the group consisting of (a) aryl, (b) substituted-aryl, (c) heteroaryl, (d) substituted-heteroaryl, (e) hydroxy, (f) C.sub.1-C.sub.6-alkoxy, (g) NR.sup.7R.sup.8 wherein R.sup.7 and R.sup.8 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.6-alkyl, or R.sup.7 and R.sup.8 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring which, when the ring is a 5- to 7-membered ring, may optionally contain a hetero function selected from the group consisting of --O--, --NH--, --N(C.sub.1-C.sub.6-alkyl-)-, --N(aryl)-, --N(aryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-aryl-C.sub.1-C.sub.6-alkyl-)-, --N(heteroaryl)-, --N(heteroaryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-heteroaryl-C.sub.1-C.sub.6-alkyl-)-,and --S-- or and--S(O).sub.n--, wherein n is 1 or 2, and (h) --CH.sub.2--M--R.sup.9 wherein M is selected from the group consisting of (i) --C(O)--NH--, (ii) --NH--C(O)--, (iii) --NH--, (iv) --N.dbd., (v) --N(CH.sub.3)--, (vi) --NH--C(O)--O-- (vii) --NH--C(O)--NH-- (viii) --O--C(O)--NH-- (ix) --O--C(O)--O-- (x) --O--, (xi) --S(O).sub.n--, wherein n is 0, 1 or 2, (xii) --C(O)--O--, (xiii) --O--C(O)--, and (xiv) --C(O)--, and R.sup.9 is selected from the group consisting of: (i) C.sub.1-C.sub.6-alkyl, optionally substituted with a substituent selected from the group consisting of (aa) aryl, (bb) substituted-aryl, (cc) heteroaryl, and (dd) substituted-heteroaryl, (ii) aryl, (iii) substituted-aryl, (iv) heteroaryl, (v) substituted-heteroaryl, and (vi) heterocycloalkyl, (3) C.sub.3-C.sub.7-cycloalkyl, (4) aryl, (5) substituted-aryl, (6) heteroaryl, and (7) substituted-heteroaryl; and R.sup.15 is selected from the group consisting of (1) C.sub.1-C.sub.12-alkyl substituted with aryl, (2) C.sub.1-C.sub.12-alkyl substituted with substituted aryl, (3) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, and (4) C.sub.1-C.sub.12-alkyl substituted with substituted heteroaryl, and R.sup.p is a hydroxyl protecting group, the method comprising (a) reductively aminating a compound having the formula ##STR00079## with an amine compound having the formula NH.sub.2--R.sup.15, wherein R.sup.15 is as previously defined; and (b) optionally deprotecting, and isolating the desired compound of the formula ##STR00080## where R.sup.e, R.sup.p and R.sup.15 are as previously defined.

15. A compound having the formula ##STR00081## where L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(3-quinolyl) and R.sup.c is H.

16. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 15 in combination with a pharmaceutically acceptable carrier.

17. A method for controlling a bacterial infection in a mammal comprising administering to a mammal, a therapeutically-effective pharmaceutical composition containing the compound of claim 15.

18. A process according to claim 7 where L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(3-quinolyl and R.sup.c is H.

19. A process according to claim 8 where L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(3-quinolyl and R.sup.c is H.
Description
TECHNICAL FIELD

This invention relates to novel semi-synthetic macrolides having antibacterial activity, to pharmaceutical compositions comprising these compounds, and to a medical method of treatment. More particularly, this invention concerns to
6-O-substituted erythromycin ketolide derivatives, compositions containing these compounds, and a method of treating bacterial infections.

BACKGROUND OF THE INVENTION

Erythromycins A through D, represented by formula (I),

TABLE-US-00001 ##STR00002## Erythromycin R' R'' A --OH --CH.sub.3 B --H --CH.sub.3 C --OH --H D --H --H

are well-known and potent antibacterial agents, used widely to treat and prevent bacterial infection. As with other antibacterial agents, however, bacterial strains having resistance or insufficient susceptibility to erythromycin have been identified. Also, erythromycin A has only weak activity against Gram-negative bacteria. Therefore, there is a continuing need to identify new erythromycin derivative compounds which possess improved antibacterial activity, which have less potential for developing resistance, which possess the desired Gram-negative activity, or which possess unexpected selectivity against target microorganisms. Consequently, numerous investigators have prepared chemical derivatives of erythromycin in an attempt to obtain analogs having modified or improved profiles of antibiotic activity.

U.S. Pat. No. 5,444,051 discloses 6-O-substituted-3-oxoerythromycin A derivatives in which the substituents are selected from alkyl, --CONH.sub.2, --CONHC(O)alkyl and --CONHSO.sub.2alkyl. PCT application WO 97/10251, published Mar. 20, 1997, discloses 6-O-methyl 3-descladinose erythromycin derivatives.

European Patent Application 596802, published May 11, 1994, discloses bicyclic 6-O-methyl-3-oxoerythromycin A derivatives.

PCT application WO 92/09614, published Jun. 11, 1992, discloses tricyclic 6-O-methylerythromycin A derivatives.

SUMMARY OF THE INVENTION

The present invention provides a novel class of 6-O-substituted erythromycin derivatives possessing increased acid stability relative to erythromycin A and 6-O-methyl erythromycin A and enhanced activity toward gram negative bacteria and macrolide resistant gram positive bacteria.

In one embodiment, the present invention provides compounds selected from the group consisting of ##STR00003## or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein either, Y and Z taken together define a group X, wherein X is selected from the group consisting of (1) .dbd.O, (2) .dbd.N--OH, (3) .dbd.N--O--R.sup.1 where R.sup.1 is selected from the group consisting of (a) unsubstituted C.sub.1-C.sub.12-alkyl, (b) C.sub.1-C.sub.12-alkyl substituted with aryl, (c) C.sub.1-C.sub.12-alkyl substituted with substituted aryl, (d) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (e) C.sub.1-C.sub.12-alkyl substituted with substituted heteroaryl, (f) C.sub.3-C.sub.12-cycloalkyl, and (g) --Si--(R.sup.2)(R.sup.3)(R.sup.4) wherein R.sup.2, R.sup.3 and R.sup.4 are each independently selected from C.sub.1-C.sub.12-alkyl and Aryl; and (4) .dbd.N--O--C(R.sup.5)(R.sup.6)--O--R.sup.1 wherein R.sup.1 is as previously defined and R.sup.5 and R.sup.6 are each independently selected from the group consisting of (a) hydrogen, (b) unsubstituted C.sub.1-C.sub.12-alkyl, (c) C.sub.1-C.sub.12-alkyl substituted with aryl, (d) C.sub.1-C.sub.12-alkyl substituted with substituted aryl, (e) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, and (f) C.sub.1-C.sub.12-alkyl substituted with substituted heteroaryl, or R.sup.5 and R.sup.6 taken together with the atom to which they are attached form a C.sub.3-C.sub.12-cycloalkyl ring; or one of Y and Z is hydrogen and the other is selected from a group consisting of (1) hydrogen, (2) hydroxy, (3) protected hydroxy, and (4) NR.sup.7R.sup.8 wherein R.sup.7 and R.sup.8 are independently selected from hydrogen and C.sub.1-C.sub.6-alkyl, or R.sup.7
and R.sup.8 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring which, when the ring is a 5- to 7-membered ring, may optionally contain a hetero function selected from the group consisting of --O--, --NH--, --N(C.sub.1-C.sub.6-alkyl-)-, --N(aryl)-, --N(aryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-aryl-C.sub.1-C.sub.6-alkyl-)-, --N(heteroaryl)-, --N(heteroaryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-heteroaryl-C.sub.1-C.sub.6-alkyl-)-, and --S-- or --S(O).sub.n-, wherein n is 1 or 2, R.sup.a is hydrogen or hydroxy; R.sup.b is selected from the group consisting of hydroxy, --O--C(O)--NH.sub.2 and --O--C(O)-imidazolyl; R.sup.c is hydrogen or a hydroxy protecting group; L is methylene or carbonyl, provided that when L is methylene, T is --O--, T is selected from the group consisting of --O--, --NH--, and --N(W--R.sup.d)-, wherein W is absent or is selected from the group consisting of --O--, --NH--CO--, --N.dbd.CH-- and --NH--; and R.sup.d is selected from the group consisting of (1) hydrogen, (2) C.sub.1-C.sub.6-alkyl optionally substituted with one or more substituents selected from the group consisting of (a) aryl, (b) substituted-aryl, (c) heteroaryl, (d) substituted-heteroaryl, (e) hydroxy, (f) C.sub.1-C.sub.6-alkoxy, (g) NR.sup.7R.sup.8, wherein R.sup.7 and R.sup.8 are as defined previously, and (h) --CH.sub.2--M--R.sup.9 wherein M is selected from the group consisting of: (i) --C(O)--NH--, (ii) --NH--C(O)--, (iii) --NH--, (iv) --N.dbd., (v) --N(CH.sub.3)--, (vi) --NH--C(O)--O-- (vii) --NH--C(O)--NH-- (viii) --O--C(O)--NH-- (ix) --O--C(O)--O-- (x) --O--, (xi) --S(O).sub.n-, wherein n is 0, 1 or 2, (xii) --C(O)--O--, (xiii) --O--C(O)--, and (xiv) --C(O)--, and R.sup.9 is selected from the group consisting of: (i) C.sub.1-C.sub.6-alkyl, optionally substituted with a substituent selected from the group consisting of (aa) aryl, (bb) substituted-aryl, (cc) heteroaryl, and (dd) substituted-heteroaryl, (ii) aryl, (iii) substituted-aryl, (iv) heteroaryl, (v) substituted-heteroaryl, and (vi) heterocycloalkyl, (3) C.sub.3-C.sub.7-cycloalkyl, (4) aryl, (5) substituted-aryl, (6) heteroaryl, and (7) substituted-heteroaryl; R is selected from the group consisting of (1) methyl substituted with a moiety selected from the group consisting of (a) CN, (b) F, (c) --CO.sub.2R.sup.10 wherein R.sup.10 is C.sub.1-C.sub.3-alkyl or aryl substituted C.sub.1-C.sub.3-alkyl, or heteroaryl substituted C.sub.1-C.sub.3-alkyl, (d) S(O).sub.nR.sup.10 where n is 0, 1 or 2 and R.sup.10 is as previously defined, (e) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (f) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are independently selected from hydrogen, C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkyl substituted with aryl, substituted aryl, heteroaryl, substituted heteroaryl, (g) aryl, (h) substituted aryl, (i) heteroaryl, and (j) substituted heteroaryl, (2) C.sub.2-C.sub.10-alkyl, (3) C.sub.2-C.sub.10-alkyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxy, (c) C.sub.1-C.sub.3-alkoxy, (d) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkoxy, (e) oxo, (f) --N.sub.3, (g) --CHO, (h) O--SO.sub.2-(substituted C.sub.1-C.sub.6-alkyl), (i) --NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are selected from the group consisting of (i) hydrogen, (ii) C.sub.1-C.sub.12-alkyl, (iii) substituted C.sub.1-C.sub.12-alkyl, (iv) C.sub.1-C.sub.12-alkenyl, (v) substituted C.sub.1-C.sub.12-alkenyl, (vi) C.sub.1-C.sub.12-alkynyl, (vii) substituted C.sub.1-C.sub.12-alkynyl, (viii) aryl, (ix) C.sub.3-C.sub.8-cycloalkyl, (x) substituted C.sub.3-C.sub.8-cycloalkyl, (xi) substituted aryl, (xii) heterocycloalkyl, (xiii) substituted heterocycloalkyl, (xiv) C.sub.1-C.sub.12-alkyl substituted with aryl, (xv) C.sub.1-C.sub.12-alkyl substituted with substituted aryl, (xvi) C.sub.1-C.sub.12-alkyl substituted with heterocycloalkyl, (xvii) C.sub.1-C.sub.12-alkyl substituted with substituted heterocycloalkyl, (xviii) C.sub.1-C.sub.12-alkyl substituted with C.sub.3-C.sub.8-cycloalkyl, (xix) C.sub.1-C.sub.12-alkyl substituted with substituted C.sub.3-C.sub.8-cycloalkyl, (xx) heteroaryl, (xxi) substituted heteroaryl, (xxii) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, and (xxiii) C.sub.1-C.sub.12-alkyl substituted with substituted heteroaryl, or R.sup.13 and R.sup.14 are taken together with the atom to which they are attached form a
3-10 membered heterocycloalkyl ring which may be substituted with one or more substituents independently selected from the group consisting of (i) halogen, (ii) hydroxy, (iii) C.sub.1-C.sub.3-alkoxy, (iv) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkoxy, (v) oxo, (vi) C.sub.1-C.sub.3-alkyl, (vii) halo-C.sub.1-C.sub.3-alkyl, and (vii) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkyl, (j) --CO.sub.2R.sup.10 wherein R.sup.10 is as previously defined, (k) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (l) .dbd.N--O--R.sup.10 wherein R.sup.10 is as previously defined, (m) --C.ident.N, (n) O--S(O).sub.nR.sup.10 wherein n is 0, 1 or 2 and R.sup.10 is as previously defined, (o) aryl, (p) substituted aryl, (q) heteroaryl, (r) substituted heteroaryl, (s) C.sub.3-C.sub.8-cycloalkyl, (t) substituted C.sub.3-C.sub.8-cycloalkyl, (u) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (v) heterocycloalkyl, (w) substituted heterocycloalkyl, (x) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (y) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (z) .dbd.N--NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (aa) .dbd.N--R.sup.9 wherein R.sup.9 is as previously defined, (bb) .dbd.N--NHC(O)R.sup.10 wherein R.sup.10 is as previously defined, and (cc) .dbd.N--NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined; (4) C.sub.3-alkenyl substituted with a moiety selected from the group consisting of (a) halogen, (b) --CHO, (c) --CO.sub.2R.sup.10 where R.sup.10 is as previously defined, (d) --C(O)--R.sup.9 where R.sup.9 is as previously defined, (e) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (f) --C.ident.N, (g) aryl, (h) substituted aryl, (i) heteroaryl, (j) substituted heteroaryl, (k) C.sub.3-C.sub.7-cycloalkyl, and (l) C.sub.1-C.sub.12-alkyl, substituted with heteroaryl, (5) C.sub.4-C.sub.10-alkenyl; (6) C.sub.4-C.sub.10-alkenyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) C.sub.1-C.sub.3-alkoxy, (c) oxo, (d) --CHO, (e) --CO.sub.2R.sup.11 where R.sup.10 is as previously defined, (f) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (g) --NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (h) .dbd.N--O--R.sup.10 where R.sup.10 is as previously defined, (i) --C.ident.N, (j) O--S(O).sub.nR.sup.10 where n is 0, 1 or 2 and R.sup.10 is as previously defined, (k) aryl, (l) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) C.sub.3-C.sub.7-cycloalkyl, (p) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (q) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (r) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (s) .dbd.N--NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (t) .dbd.N--R.sup.9 wherein R.sup.9 is as previously defined, (u) .dbd.N--NHC(O)R.sup.10 where R.sup.10 is as previously defined, and (v) .dbd.N--NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined; (7) C.sub.3-C.sub.10-alkynyl; and (8) C.sub.3-C.sub.10-alkynyl substituted with one or more substituents selected from the group consisting of (a) trialkylsilyl, (b) aryl, (c) substituted aryl, (d) heteroaryl, and (e) substituted heteroaryl; and A, B, D and E, with the provision that at least two of A, B, D and E are hydrogen, are independently selected from the group consisting of: (a) hydrogen; (b) C.sub.1-C.sub.6-alkyl, optionally substituted with one or more substituents selected from the group consisting of: (i) aryl; (ii) substituted-aryl; (ii) heteroaryl; (iv) substituted-heteroaryl; (v) heterocycloalkyl; (vi) hydroxy; (vii) C.sub.1-C.sub.6-alkoxy; (viii) halogen consisting of Br, Cl, F or I; and (ix) NR.sup.7R.sup.8, where R.sup.7 and R.sup.8 are as previously defined; (c) C.sub.3-C.sub.7-cycloalkyl; (d) aryl; (e) substituted-aryl; (f) heteroaryl; (g) substituted-heteroaryl; (h) heterocycloalkyl; and (i) a group selected from option (b) above further substituted with --M--R.sup.9, wherein M and R.sup.9 are as previously defined; or any one pair of substituents, consisting of AB, AD, AE, BD, BE or DE, is taken together with the atom or atoms to which they are attached to form a 3- to 7-membered ring optionally containing a hetero function selected from the group consisting of --O--, --NH--, --N(C.sub.1-C.sub.6-alkyl-)-, --N(aryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-aryl-C.sub.1-C.sub.6-alkyl-)-, --N(heteroaryl-C.sub.1-C.sub.6-alkyl-)-, --N(substituted-heteroaryl-C.sub.1-C.sub.6-alkyl-)-, --S-- or --S(O).sub.n-, wherein n is 1 or 2, --C(O)--NH--, --C(O)--NR.sup.12--, wherein R.sup.12 is as previously defined, --NH--C(O)--, --NR.sup.12--C(O)--, wherein R.sup.12 is as previously defined, and --C(.dbd.NH)--NH--.

The present invention also provides pharmaceutical compositions which comprise a therapeutically effective amount of a compound as defined above in combination with a pharmaceutically acceptable carrier.

The invention further relates to a method of treating bacterial infections in a host mammal in need of such treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound as defined above.

In a further aspect of the present invention are provided processes for the preparation of 6-O-substituted macrolide derivatives of Formula (II), (III), (IV), (IV-A) and (V) above.

DETAILED DESCRIPTION OF THE INVENTION

In one embodiment of the present invention are compounds having the formula II, ##STR00004## wherein X, Y, R, Ra and Rc are as described previously.

A representative compound of formula II is the compound of Formula (II), R.sup.a is OH, R.sup.c is benzoyl, R is allyl.

In a preferred embodiment of the compounds of formula II of the invention are compounds wherein R.sup.a is hydroxy and R.sup.c is hydrogen.

In a more preferred embodiment of the compounds of formula II of the invention are compounds having the formula VIII, ##STR00005## wherein X is O or NOH, and R is as defined previously.

Compounds representative of this embodiment include, but are not limited to: Compound of Formula (VIII): X is O, R is allyl; Compound of Formula (VIII): X is NOH, R is allyl; Compound of Formula (VIII): X is O, R is propyl; Compound of Formula (VIII): X is O, R is --CH.sub.2CHO; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.NOH; Compound of Formula (VIII): X is NOH, R is --CH.sub.2CH.dbd.NOH; Compound of Formula (VIII): X is O, R is --CH.sub.2CN; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2NH.sub.2; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2NHCH.sub.2-Phenyl; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2-Phenyl; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2NHCH(CO.sub.2CH.sub.3)CH.sub.2-Phenyl; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2NHCH.sub.2-(4-pyridyl); Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2NHCH.sub.2-(4-quinolyl); Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CH-Phenyl; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2CH.sub.2-Phenyl; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CH-(4-methoxyphenyl); Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CH-(4-chlorophenyl); Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2CH.sub.2OH; Compound of Formula (VIII): X is O, R is --CH.sub.2C(O)OH; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2NHCH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2NHCH.sub.2OH; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2N(CH.sub.3).sub.2; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2(1-morpholinyl); Compound of Formula (VIII): X is O, R is --CH.sub.2C(O)NH.sub.2; Compound of Formula (VIII): X is O, R is --CH.sub.2NHC(O)NH.sub.2; Compound of Formula (VIII): X is O, R is --CH.sub.2NHC(O)CH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2F; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2OCH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CH(CH.sub.3).sub.2; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2CH(CH.sub.3)CH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2OCH.sub.2CH.sub.2OCH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2SCH.sub.3; Compound of Formula (VIII): X is O, R is -cyclopropyl; Compound of Formula (VIII): X is O, R is --CH.sub.2OCH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2F; Compound of Formula (VIII): X is O, R is --CH.sub.2-cyclopropyl; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2CHO; Compound of Formula (VIII): X is O, R is --C(O)CH.sub.2CH.sub.2CH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2-(4-nitrophenyl); Compound of Formula (VIII): X is O, R is --CH.sub.2-(4-chlorophenyl); Compound of Formula (VIII): X is O, R is --CH.sub.2-(4-methoxyphenyl); Compound of Formula (VIII): X is O, R is --CH.sub.2-(4-cyanophenyl); Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CHC(O)OCH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CHC(O)OCH.sub.2CH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CHCH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CHCH.sub.2CH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CHCH.sub.2CH.sub.2CH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CHSO.sub.2-phenyl; Compound of Formula (VIII): X is O, R is --CH.sub.2C.ident.C--Si(CH.sub.3).sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2C.ident.CCH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2C.ident.CCH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2-(2-pyridyl); Compound of Formula (VIII): X is O, R is --CH.sub.2-(3-pyridyl); Compound of Formula (VIII): X is O, R is --CH.sub.2-(4-pyridyl); Compound of Formula (VIII): X is O, R is --CH.sub.2-(4-quinolyl); Compound of Formula (VIII): X is O, R is --CH.sub.2NO.sub.2; Compound of Formula (VIII): X is O, R is --CH.sub.2C(O)OCH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2C(O)-phenyl; Compound of Formula (VIII): X is O, R is --CH.sub.2C(O)CH.sub.2CH.sub.3; Compound of Formula (VIII): X is O, R is --CH.sub.2Cl; Compound of Formula (VIII): X is O, R is --CH.sub.2S(O).sub.2-phenyl; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CHBr; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CH-(4-quinolyl); Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2CH.sub.2-(4-quinolyl); Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CH-(5-quinolyl); Compound of Formula (VIII): X is O, R is --CH.sub.2CH.sub.2CH.sub.2-(5-quinolyl); Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CH-(4-benzoxazolyl); Compound of Formula (VIII): X is O, R is -CH.sub.2CH.dbd.CH-(7-benzimidazolyl); Compound of Formula (VIII): X is O, R is CH.sub.2-(3-iodophenyl); Compound of Formula (VIII): X is O, R is CH.sub.2-(2-naphthyl); Compound of Formula (VIII): X is O, R is CH.sub.2--CH.dbd.CH-(4-fluorophenyl); and Compound of Formula (VIII): X is O, R is CH.sub.2--CH(OH)--CN.

Preferred compounds of formula VIII are selected from the group consisting of: Compound of Formula (VIII): X is O, R is allyl; Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CH-phenyl; and Compound of Formula (VIII): X is O, R is --CH.sub.2CH.dbd.CH-(3-quinolyl).

In one embodiment of the invention is a process for the preparation of 6-O-substituted macrolide compounds having the Formula: ##STR00006## wherein either, Y, Z, R.sup.a, R.sup.c, and R are previously defined, the method comprising: (a) treating a compound having the formula ##STR00007## wherein R.sup.p is a hydroxy protecting group and V is .dbd.N--O--R.sup.1 or .dbd.N--O--C(R.sup.5)(R.sup.6)--O--R.sup.1 wherein R.sup.1, R.sup.9 and R.sup.10 are as previously defined, with a base in an aprotic solvent followed by treatment with an alkylating agent to give a compound having the formula ##STR00008## wherein R.sup.a and R.sup.p are as previously defined, V is .dbd.N--O--R.sup.1 or .dbd.N--O--C(R.sup.5)(R.sup.6)--O--R.sup.1 wherein R.sup.1, R.sup.5 and R.sup.6 are as previously defined, and R is the "alkyl group" derived from the corresponding alkylating agent; (b) deprotecting the 2'- and 4''-hydroxyl groups to give a compound of the formula ##STR00009## wherein R.sup.a is as previously defined and R is the "alkyl group" derived from the corresponding alkylating agent; (c) deoximation in the presence of acid in a suitable solvent to give the desired intermediate having the formula ##STR00010## (d) removing the cladinose moiety by hydrolysis with acid, and protecting the 2' hydroxyl group by treatment with a hydroxy-protecting reagent to give a 3-hydroxy erythromycin compound having the formula ##STR00011## (e) oxidizing the 3-hydroxy group, optionally deprotecting the 2'-hydroxyl group, and isolating the desired compound.

In a preferred embodiment of the process immediately above, in step (a) the base is selected from the group consisting of potassium hydroxide, cesium hydroxide, tetraalkylammonium hydroxide, sodium hydride, potassium hydride, potassium isopropoxide, potassium tert-butoxide and potassium isobutoxide, the alkylating agent is selected from the group consisting of allyl bromide, propargyl bromide, benzyl bromide, 2-fluoroethyl bromide, 4-nitrobenzyl bromide, 4-chlorobenzyl bromide,
4-methoxybenzyl bromide, .alpha.-bromo-p-tolunitrile, cinnamyl bromide, methyl 4-bromocrotonate, crotyl bromide, 1-bromo-2-pentene, 3-bromo-1-propenyl phenyl sulfone, 3-bromo-1-trimethylsilyl-1-propyne, 3-bromo-2-octyne, 1-bromo-2-butyne, 2-picolyl chloride, 3-picolyl chloride, 4-picolyl chloride, 4-bromomethyl quinoline, bromoacetonitrile, epichlorohydrin, bromofluoromethane, bromonitromethane, methyl bromoacetate, methoxymethyl chloride, bromoacetamide, 2-bromoacetophenone, 1-bromo-2-butanone, bromo chloromethane, bromomethyl phenyl sulfone, 1,3-dibromo-1-propene, allyl O-tosylate, 3-phenylpropyl-O-trifluoromethane sulfonate, and n-butyl-O-methanesulfonate, and the reaction is performed at a temperature from about -15.degree. C. to about
50.degree. C. for a period from 0.5 hours to 10 days; in step (b) deprotection is accomplished by use of acetic acid in water and acetonitrile; and in step (c) the deoximating reagent is an inorganic sulfur oxide compound is selected from the group consisting of sodium hydrogen sulfite, sodium pyrosulfate, sodium thiosulfate, sodium sulfate, sodium sulfite, sodium hydrosulfite, sodium metabisulfite, sodium dithionate, potassium thiosulfate, and potassium metabisulfite, or an inorganic nitrite salt in the presence of acid selected from the group consisting of sodium nitrite and potassium nitrite, and the solvent is selected from the group consisting of water, methanol, ethanol, propanol, isopropanol, trimethylsilanol or a mixture of one or more thereof; in step (d) the hydroxy protecting reagent is selected from the group consisting of a trialkysilyl halide, an acyl anhydride or an acyl halide; in step (e), the oxidizing is selected from N-chlorosuccinimide-dimethyl sulfide and carbodiimide-dimethylsulfoxide, and the optional deprotection is carried out by stirring in methanol.

In another embodiment of the present invention are compounds having formula III, ##STR00012## wherein R, R.sup.c, L and T are as described previously.

Preferred compounds of formula III are those selected from the group consisting of: Compound of Formula (III); R.sup.c is acetyl, L is CO, T is NH, R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (III): R.sup.c is acetyl, L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (III): R.sup.c is benzoyl, L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (III): R.sup.c is propanoyl, L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); and Compound of Formula (III): R.sup.c is ethylsuccinoyl, L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-quinolyl).

In a more preferred embodiment of the compounds of formula III of the invention are compounds having the formula IX. ##STR00013## wherein L, T, and R are defined above.

Compounds representative of this embodiment include, but are not limited to: Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-phenyl; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2CH.sub.2-Phenyl; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-chlorophenyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2CH.sub.3; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2NH.sub.2; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.NOH; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2CH.sub.2OH; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2F; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2-(4-pyridyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2-(4-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH(OH)CN; Compound of Formula (IX): L is CO, T is O, R is --CH(C(O)OCH.sub.3)CH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CN; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-methoxyphenyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-fluorophenyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(8-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2NHCH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2-(4-pyridyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2-(4-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-pyridyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2CH.sub.2-(4-pyridyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2CH.sub.2-(4-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(5-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.sub.2CH.sub.2-(5-quinolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-benzoxazolyl); Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(4-benzimidazolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-Phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.3; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NH.sub.2; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOH; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.2OH; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2F; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2-(4-pyridyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH(OH)CN; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2-(4-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH(C(O)OCH.sub.3)CH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CN; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-clorophenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-fluorophenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.2-(4-methoxyphenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-methoxyphenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-chloro-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2-(2-chlorophenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2-(4-pyridyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2-(4-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-pyridyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.2-(4-pyridyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-fluoro-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.2-(4-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-cyano-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.2-(5-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-benzoxazolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-benzimidazolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-methoxy-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2-(2-naphthyl); Compound of Formula (IX): L is CO, T is N(CH.sub.3), R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is N(CH.sub.3), R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is N(CH.sub.2CH.sub.2N(CH.sub.3).sub.2), R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is N(CH.sub.2CH.sub.2N(CH.sub.3).sub.2), R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is N(CH.sub.2CH.dbd.CH.sub.2), R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is T is N(CH.sub.2CH.dbd.C-(3-quinolyl)), R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-pyridyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-isoquinolinyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3,4-methylenedioxyphenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(8-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(5-indolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-chloro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3,4-ethylenedioxyphenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-nitrophenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-nitroquinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(5-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(2-methyl-6-quinolyl); Compound of Formula (III): L is CO, T is NH, R.sup.c is acetyl; R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(5-isoquinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(7-nitro-6-quinoxalinyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-amino-3-quiolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(1,8-naphthyridin-3-yl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-(acetylamino)-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-carbazolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(5-benzimidazolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-hydroxy-2-(N-(2-methoxyphenyl)amido)-7-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-quinoxalinyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-hydroxy-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-methoxy-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(5-nitro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(8-nitro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(2-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-carboxyl-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-fluoro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-methoxycarbonyl-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-aminocarbonyl-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-cyano-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-bromo-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2C(O)H; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2Phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2Phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2CH.sub.2-Phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2CH.sub.2CH.sub.2Phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2CH.sub.2-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHCH.sub.2(6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NO(phenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2(phenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2(4-NO.sub.2-phenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2(4-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2(2-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2-(6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2-(1-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NOCH.sub.2-(2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHOCH.sub.2-(phenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2NHOCH.sub.2-(4-NO.sub.2-phenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2C(O)-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2C(O)-(4-F-phenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.NNHC(O)phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.2-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2-(2-(3-quinolyl)cyclopropyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C--H; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(6-nitro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-naphthyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(6-methoxy-2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(6-chloro-2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(2-methyl-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(5-(N-(2-pyridyl)amino)carbonyl)furanyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(1-phenylethenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C--Br; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2-(2,2-dimethyl-1,3-dioxolan-4-yl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH(OH)-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH(OH)CH.sub.2OH; Compound of Formula (IX): L is CO, T is NHNH.sub.2, R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is NHNH.sub.2, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is NHNH.sub.2, R is --CH.sub.2CH.sub.2CH.sub.2-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-naphthyl; Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(3-(2-furanyl)-6-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(8-chloro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(4-chloro-2-trifluoromethyl-6-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(9-fluorenone-2-yl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(6-benzoyl-2-naphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(7-methoxy-2-naphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(3-phenyl-6-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(3-(2-pyridyl)-6-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(3-(2-thiophenyl)-6-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(4-methylnaphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(6-.beta.-D-galactopyranosyl-2-naphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(7-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(4-fluoronaphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(3-biphenyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(5-nitronaphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(4-pyrrolylphenyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(6-methoxy-2-naphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(3,5-dichlorophenyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2-(3-iodophenyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2-(3-(2-furanyl)phenyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(6-hydroxy-2-naphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(6-(2-bromoethoxy)-2-naphthyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(6-(2-(tetrazolyl)ethoxy-2-naphthyl), Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-naphthyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(2-phenylethenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--CH.dbd.CH-(5-(3-isoxazolyl)-2-thiophenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--CH.dbd.CH-(1,3-dimethyl-2,4-dioxo-5-pyrimidinyl); and Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--CH.dbd.CH-(5-(2-pyridyl)aminocarbonyl-2-furanyl).

Preferred compounds of formula IX are those selected from the group consisting of: Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-Phenyl; Compound of Formula (IX): L is CO, T is O, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-Phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is N(CH.sub.3), R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is N(CH.sub.3), R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is N(CH.sub.2CH.sub.2N(CH.sub.3).sub.2), R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is N(CH.sub.2CH.sub.2N(CH.sub.3).sub.2), R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-pyridyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-isoquinolinyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3,4-methylenedioxyphenyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(8-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-nitroquinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(5-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-amino-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(1,8-naphthyridin-3-yl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-(acetylamino)-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-quinoxalinyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-hydroxy-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-methoxy-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(5-nitro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(8-nitro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(2-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(4-carboxyl-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-fluoro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-methoxycarbonyl-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-aminocarbonyl-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(6-cyano-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.dbd.CH-(3-bromo-6-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2CH.sub.2CH.sub.2-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2-(2-(3-quinolyl)cyclopropyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C--H; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(6-nitro-3-quinolyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-phenyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-napthyl; Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(6-methoxy-2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(6-chloro-2-naphthyl); Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--C.ident.C-(6-quinolyl); Compound of Formula (IX): L is CO, T is N(NH.sub.2), R is --CH.sub.2CH.dbd.CH.sub.2; Compound of Formula (IX): L is CO, T is N(NH.sub.2), R is --CH.sub.2CH.dbd.CH-(3-quinolyl); Compound of Formula (IX): L is CO, T is N(NH.sub.2), R is --CH.sub.2CH.sub.2CH.sub.2-(3-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-naphthyl; Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(3-(2-pyridyl)-6-quinolyl); Compound of Formula (IX): L is CO, T is NH.sub.2, R is --CH.sub.2CH.dbd.CH-(7-quinolyl); and Compound of Formula (IX): L is CO, T is NH, R is --CH.sub.2--CH.dbd.CH-(5-(3-isoxazolyl)-2-thiophenyl).

In another embodiment of the invention is a process for the preparation of 6-O-substituted macrolide compounds having the Formula: ##STR00014## wherein R and R.sup.p R is selected from the group consisting of (1) methyl substituted with a moiety selected from the group consisting of (a) CN, (b) F, (c) --CO.sub.2R.sup.10 wherein R.sup.10 is C.sub.1-C.sub.3-alkyl or aryl substituted C.sub.1-C.sub.3-alkyl, or heteroaryl substituted C.sub.1-C.sub.3-alkyl, (d) S(O).sub.nR.sup.10 where n is 0, 1 or 2
and R.sup.10 is as previously defined, (e) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (f) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are independently selected from hydrogen, C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkyl substituted with aryl, substituted aryl, heteroaryl, substituted heteroaryl, (g) aryl, (h) substituted aryl, (i) heteroaryl, and (j) substituted heteroaryl, (2) C.sub.2-C.sub.10-alkyl, (3) C.sub.2-C.sub.10-alkyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxy, (c) C.sub.1-C.sub.3-alkoxy, (d) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkoxy, (e) oxo, (f) --N.sub.3, (g) --CHO, (h) O--SO.sub.2-(substituted C.sub.1-C.sub.6-alkyl), (i) --NR.sup.13R.sup.14
wherein R.sup.13 and R.sup.14 are selected from the group consisting of (i) hydrogen, (ii) C.sub.1-C.sub.12-alkyl, (iii) substituted C.sub.1-C.sub.12-alkyl, (iv) C.sub.1-C.sub.12-alkenyl, (v) substituted C.sub.1-C.sub.12-alkenyl, (vi) C.sub.1-C.sub.12-alkynyl, (vii) substituted C.sub.1-C.sub.12-alkynyl, (viii) aryl, (ix) C.sub.3-C.sub.8-cycloalkyl, (x) substituted C.sub.3-C.sub.8-cycloalkyl, (xi) subtituted aryl, (xii) heterocycloalkyl, (xiii) substituted heterocycloalkyl, (xiv) C.sub.1-C.sub.12-alkyl substituted with aryl, (xv) C.sub.1-C.sub.12-alkyl substituted with substituted aryl, (xvi) C.sub.1-C.sub.12-alkyl substituted with heterocycloalkyl, (xvii) C.sub.1-C.sub.12-alkyl substituted with substituted heterocycloalkyl, (xviii) C.sub.1-C.sub.12-alkyl substituted with C.sub.3-C.sub.8-cycloalkyl, (xix) C.sub.1-C.sub.12-alkyl substituted with substituted C.sub.3-C.sub.8-cycloalkyl, (xx) heteroaryl, (xxi) substituted heteroaryl, (xxii) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, and (xxiii) C.sub.1-C.sub.12-alkyl substituted with substituted heteroaryl, or R.sup.13 and R.sup.14 are taken together with the atom to which they are attached form a 3-10 membered heterocycloalkyl ring which may be substituted with one or more substituents independently selected from the group consisting of (i) halogen, (ii) hydroxy, (iii) C.sub.1-C.sub.3-alkoxy, (iv) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkoxy, (v) oxo, (vi) C.sub.1-C.sub.3-alkyl, (vii) halo-C.sub.1-C.sub.3-alkyl, and (vii) C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkyl, (j) --CO.sub.2R.sup.10 wherein R.sup.10 is as previously defined, (k) --C(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (l) .dbd.N--O--R.sup.10 wherein R.sup.10 is as previously defined, (m) --C.ident.N, (n) O--S(O).sub.nR.sup.10 wherein n is 0, 1 or 2 and R.sup.10 is as previously defined, (o) aryl, (p) substituted aryl, (q) heteroaryl, (r) substituted heteroaryl, (s) C.sub.3-C.sub.8-cycloalkyl, (t) substituted C.sub.3-C.sub.8-cycloalkyl, (u) C.sub.1-C.sub.12-alkyl substituted with heteroaryl, (v) heterocycloalkyl, (w) substituted heterocycloalkyl, (x) NHC(O)R.sup.10 where R.sup.10 is as previously defined, (y) NHC(O)NR.sup.11R.sup.12 wherein R.sup.11 and R.sup.12 are as previously defined, (z) .dbd.N--NR.sup.13R.sup.14 wherein R.sup.13 and R.sup.14 are as previously defined, (aa) .dbd.N--R.sup.9 wherein R.sup.9 is as pre