Macrolide immunomodulators

Claim 2

A compound of the formula: ##STR19## wherein R 1 is hydrogen, a hydroxy protecting group, loweralkyl or phenyl-substituted loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3)═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is hydrogen; R 9 is (1) --OS(O) 2 CF 3 , (2) --OS(O) 2 F, (3) --OS(O) 2 R 21a wherein R 21a is loweralkyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, (4) --OC(O)R 23 wherein R 23 is loweralkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclic, heterocyclicalkyl, alkoxy, --O-cycloalkyl, --O-aryl, --O--heterocyclic, --O--(N-succinimidyl) or 5-tetrazolyl; (5) --OC(O)--N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O)2NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--loweralkyl, (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, (6) --OR 25 wherein R 25 is as defined above, (7) a protected hydroxy group, (8) --OC(O)N(OR 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (9) --O(CH 2 ) i C(O)OR 20 wherein i is one or two and R 20 is independently defined as above, (10) --O(CH(Si(CH 3 ) 3 ))--(CH 2 ) j C(O)OR 20 wherein j is zero or one R 20 is independently defined as above, (11) --O(CH 2 ) i C(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (12) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (13) --O(CH 2 ) i C(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (14) --O(CH 2 ) i NHC(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (15) --O(CH 2 ) i NHC(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (16) --O(CH 2 ) i NHC(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (17) --OS(O) 2 N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (18) --O(CH 2 ) i --NHC(O)R 24 wherein R 24 is defined as above, (19) --OCH(R 24 )--SH wherein R 24 is defined as above, (20) --OCH(R 24 )--S--loweralkyl wherein R 24 is defined as above, (21) --OCH(R 24 )--S--aryl wherein R 24 is defined as above and (22) --N 3 ; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

Claim 3

A compound according to claim 1 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 are defined as above; R 8 is hydrogen; R 9 is defined as above; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 4

A compound according to claim 1 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are (1) oxo, (2) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (3) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is hydrogen; R 9 is (1) --OH, (2) --OC(O)R 23 wherein R 23 is --O-aryl, --O--(N-succinimidyl), --O-benzotriazolyl, --O--2'-pyridyl or 5-tetrazolyl, (3) --OC(O)--N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--,--S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and--NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--loweralkyl, (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyI or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, (4) --OC(O)N(OR 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (5) --O(CH 2 ) i C(O)N(R 24 )(R 25 ) wherein iis one or two and R 24 and R 25 are defined as above, (6) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (7) --O(CH 2 ) i NHC(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above or (8) --O(CH 2 ) i NHC(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; and X and Y token together are oxo.

Claim 5

A compound according to claim 1 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are (1) oxo, (2) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (3) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is hydrogen; R 9 is (1) --OH, (2) --OC(O)R 23 wherein R 23 is -0-aryl, --O--(N-succinimidyl), --O-- benzotriazolyl, --O--2'-pyridyl or 5-tetrazolyl, (3) --OC(O)--N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O)2NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and--NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O-loweralkyl, (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, (4) --OC(O)N(OR 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (5) --O(CH 2 ) i C(O)N(R 24 )(R 25 ) wherein iis one or two and R 24 and R 25 are defined as above, (6) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (7) --O(CH 2 ) i NHC(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above or (8) --O(CH 2 ) i NHC(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 6

A compound according to claim 1 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are oxo; R 8 is hydrogen; R 9 is --OH, --O-loweralkyl or --OC(O)N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 7

A compound of the formula: ##STR20## wherein R 1 is hydrogen, a hydroxy protecting group, loweralkyl or phenyl-substituted loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is hydrogen; R 9 is (1) --SR 24 wherein R 24 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --C(O)--O-loweralkyl, (j) --C(O)-aryl, (k) --C(O)-heterocyclic or (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl, (2) --SC(═NH)--NH 2 , (3) --SC(═N--NH 2 )--NH 2 , (4) --Se-phenyl or (5) --Se(O)-phenyl; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is loweralkyl, aryl or heterocyclic or R 10a and R 10b token together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

Claim 8

A compound of the formula: ##STR20## wherein R 1 is hydrogen, a hydroxy protecting group, loweralkyl or phenyl-substituted loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is hydrogen; R 9 is (1) --SR 24 wherein R 24 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --C(O)--O-loweralkyl, (j) --C(O)-aryl, (k) --C(O)-heterocyclic or (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl, (2) --SC(═NH)--NH 2 , (3) --SC(═N--NH 2 )--NH 2 , (4) --Se-phenyl or (5) --Se(O)-phenyl; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is loweralkyl, aryl or heterocyclic or R 10a and R 10b token together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

Claim 9

A compound according to claim 6 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 are defined as above; R 8 is hydrogen; R 9 is --SR 24 wherein R 24 is defined as above; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 10

A compound according to claim 6 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are (1) oxo, (2) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (3) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is hydrogen; R 9 is --SR 24 wherein R 24 is hydrogen, loweralkyl, substituted loweralkyl as defined above, aryl or heterocyclic; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 11

A compound according to claim 6 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are oxo; R 8 is hydrogen; R 9 is --SR 24 wherein R 24 is hydrogen, loweralkyl, substituted loweralkyl as defined above, aryl or heterocyclic; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 12

A compound according to claim 6 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are oxo; R 8 is hydrogen; R 9 is --SR 24 wherein R 24 is hydrogen, imidazol-2-yl or N-methyl-imidazol-2-yl; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 13

A compound of the formula: ##STR21## wherein R 1 is hydrogen, a hydroxy protecting group, loweralkyl or phenyl-substituted loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclic alkyl; R 8 is hydrogen; R 9 is (1) --N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--loweralkyl, (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl, (2) --N═C═O, (3)--NHC(O)--R* or (4) --NHS(O) 2 -R* wherein R* is (a) loweralkyl, (b) cycloalkyl, (c) aryl, (d) heterocyclic, (e) loweralkyl substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C (NR 27 )NHNH-- and--NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (f) --N(R a )(R b ) wherein R a and R b are independently selected from hydrogen, loweralkyl and --N(R c )(R d ) wherein R c and R d are independently selected from hydrogen and loweralkyl or (g) --OR* wherein R* is defined as above; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 11 is loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

Claim 14

A compound of the formula: ##STR21## wherein R 1 is hydrogen, a hydroxy protecting group, loweralkyl or phenyl-substituted loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclic alkyl; R 8 is hydrogen; R 9 is (1) --N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--loweralkyl, (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl, (2) --N═C═O, (3)--NHC(O)--R* or (4) --NHS(O) 2 -R* wherein R* is (a) loweralkyl, (b) cycloalkyl, (c) aryl, (d) heterocyclic, (e) loweralkyl substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C (NR 27 )NHNH-- and--NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (f) --N(R a )(R b ) wherein R a and R b are independently selected from hydrogen, loweralkyl and --N(R c )(R d ) wherein R c and R d are independently selected from hydrogen and loweralkyl or (g) --OR* wherein R* is defined as above; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 11 is loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

Claim 15

A compound according to claim 11 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 are defined as above; R 8 is hydrogen; R 9 is --N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 16

A compound according to claim 11 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are (1) oxo, (2) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (3) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is hydrogen; R 9 is --N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from hydrogen, loweralkyl, substituted loweralkyl as defined above, --NHC(O)--O--loweralkyl, --NHC(O)-aryl and --NHC(O)-heterocyclic or R 24 and R 25 taken together form a heterocyclic ring; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 17

A compound according to claim 11 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are oxo; R 8 is hydrogen; R 9 is --N (R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from hydrogen, loweralkyl, substituted loweralkyl as defined above, --NHC(O)--O--loweralkyl,, --NHC(O)-aryl and--NHC(O)-heterocyclic or R 24 and R 25 taken together form a heterocyclic ting; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 18

A compound according to claim 11 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are oxo; R 8 is hydrogen; R 9 is --NH 2 , 2-pyridon-1-yl or 4-pytidon-1-yl; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 19

A compound of the formula: ##STR22## R 1 is hydrogen, a hydroxy protecting group, loweralkyl or phenyl-substituted loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2 ) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclic alkyl; R 8 , R 9 , R 18 and R 19 are independently selected from (1) hydrogen, (2) --OS(O) 2 CF 3 , (3) --OS(O) 2 F, (4) --OS (O) 2 R 21 a wherein R 21a is loweralkyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, (5) --OC(O)R 23 wherein R 23 is --O-aryl, --O-(N-succinimidyl), --O-benzotriazolyl, --O-2'-pyridyl or 5-tetrazolyl; (6) --OC(O)--N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and--NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x)--S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--loweralkyl, (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, (7) --OR 25 wherein R 25 is as defined above, (8) a protected hydroxy group, (9) --OC(O)N(OR 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (10) --O(CH 2 ) i C(O)OR 20 wherein i is one or two and R 20 is independently defined as above, (11) --O(CH(Si(CH 3 ) 3 ))--(CH 2 ) j C(O)OR 20 wherein j is zero or one and R 20 is independently defined as above, (12) --O(CH 2 ) i C(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (13) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (14) --O(CH 2 ) i C(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (15) --O(CH 2 ) i NHC(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (16) --O(CH 2 ) i NHC(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (17) --O(CH 2 ) i NHC(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (18) --OS(O) 2 N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (19) --O(CH 2 ) i --NHC(O)R 24 wherein R 24 is defined as above, (20) --OCH(R 24 )--SH wherein R 24 is defined as above, (21) --OCH(R 24 )--S-loweralkyl wherein R 24 is defined as above, (22) --OCH(R 24 )--S--aryl wherein R 24 is defined as above, (23) --N 3 , (24) --N═C═O, (25) --N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (26) --NHC(O)--R 24 wherein R 24 is defined as above, (27) --NHC(O)--N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (28) --S--R 24 wherein R 24 is defined as above and (29) --S--q-R 24 wherein q is a divalent radical selected from the group consisting of--S--, --C(O)--, --C(O)--O--, --C(O)--NH--and--C(N(R 27 ))--NHNH-- and R 24 and R 27 are defined as above, with the proviso that one of R 8 and R 9 is hydrogen and the other is not hydrogen and one of R 18 and R 19 is hydrogen and the other is not hydrogen; or R 8 and R 9 taken together are (1) oxo, (2) ═N--O--R 24 wherein R 24 is defined as above or (3) ═N--N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above; or R 18 and R 19 taken together are (1) oxo, (2) ═N--O--R 24 wherein R 24 is independently defined as above or (3) ═N--N(R 24 )(R 25 ) wherein R 24 and R 25 are independently defined as above; or one of R 8 and R 9 token together with one of R 18 and R 19 form a heterocyclic ring with the others of R 8 , R 9 , R 18 and R 19 being hydrogen or together forming a bond; or R 8 and R 18 are hydrogen and R 8 and R 19 form a bond; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

Claim 20

A compound of the formula: ##STR22## R 1 is hydrogen, a hydroxy protecting group, loweralkyl or phenyl-substituted loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2 ) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclic alkyl; R 8 , R 9 , R 18 and R 19 are independently selected from (1) hydrogen, (2) --OS(O) 2 CF 3 , (3) --OS(O) 2 F, (4) --OS (O) 2 R 21 a wherein R 21a is loweralkyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, (5) --OC(O)R 23 wherein R 23 is --O-aryl, --O-(N-succinimidyl), --O-benzotriazolyl, --O-2'-pyridyl or 5-tetrazolyl; (6) --OC(O)--N(R 24 )(R 25 ) wherein R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and--NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x)--S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--loweralkyl, (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, (7) --OR 25 wherein R 25 is as defined above, (8) a protected hydroxy group, (9) --OC(O)N(OR 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (10) --O(CH 2 ) i C(O)OR 20 wherein i is one or two and R 20 is independently defined as above, (11) --O(CH(Si(CH 3 ) 3 ))--(CH 2 ) j C(O)OR 20 wherein j is zero or one and R 20 is independently defined as above, (12) --O(CH 2 ) i C(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (13) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (14) --O(CH 2 ) i C(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (15) --O(CH 2 ) i NHC(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (16) --O(CH 2 ) i NHC(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (17) --O(CH 2 ) i NHC(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (18) --OS(O) 2 N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (19) --O(CH 2 ) i --NHC(O)R 24 wherein R 24 is defined as above, (20) --OCH(R 24 )--SH wherein R 24 is defined as above, (21) --OCH(R 24 )--S-loweralkyl wherein R 24 is defined as above, (22) --OCH(R 24 )--S--aryl wherein R 24 is defined as above, (23) --N 3 , (24) --N═C═O, (25) --N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (26) --NHC(O)--R 24 wherein R 24 is defined as above, (27) --NHC(O)--N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above, (28) --S--R 24 wherein R 24 is defined as above and (29) --S--q-R 24 wherein q is a divalent radical selected from the group consisting of--S--, --C(O)--, --C(O)--O--, --C(O)--NH--and--C(N(R 27 ))--NHNH-- and R 24 and R 27 are defined as above, with the proviso that one of R 8 and R 9 is hydrogen and the other is not hydrogen and one of R 18 and R 19 is hydrogen and the other is not hydrogen; or R 8 and R 9 taken together are (1) oxo, (2) ═N--O--R 24 wherein R 24 is defined as above or (3) ═N--N(R 24 )(R 25 ) wherein R 24 and R 25 are defined as above; or R 18 and R 19 taken together are (1) oxo, (2) ═N--O--R 24 wherein R 24 is independently defined as above or (3) ═N--N(R 24 )(R 25 ) wherein R 24 and R 25 are independently defined as above; or one of R 8 and R 9 token together with one of R 18 and R 19 form a heterocyclic ring with the others of R 8 , R 9 , R 18 and R 19 being hydrogen or together forming a bond; or R 8 and R 18 are hydrogen and R 8 and R 19 form a bond; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

Claim 21

A compound according to claim 16 wherein Z is ##STR23## R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 are defined as above; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 22

A compound according to claim 16 wherein Z is ##STR24## R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are (1)oxo, (2) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (3) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclic alkyl; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 23

A compound according to claim 16 wherein Z is ##STR25## R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are (1) oxo, (2) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (3) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 24

A compound according to claim 16 wherein Z is ##STR26## R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are oxo; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 25

A compound of the formula: ##STR27## wherein R 1 is hydrogen, a hydroxy protecting group, loweralkyl or phenyl-substituted loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 token together are oxo; R 4 is hydrogen or phenyl-substituted loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is (1) --OC(O)N(OR 20 )(R 24 ) or (2) --O--C(O)--NHN(R 24 )(R 25 ) wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl or heterocyclic, each of which is optionally substituted with loweralkyl, hydroxy, aryl or heterocyclic and R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--,--NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--loweralkyl, (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic or (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group; R 9 is hydrogen; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

Claim 26

A compound of the formula: ##STR27## wherein R 1 is hydrogen, a hydroxy protecting group, loweralkyl or phenyl-substituted loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 token together are oxo; R 4 is hydrogen or phenyl-substituted loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is (1) --OC(O)N(OR 20 )(R 24 ) or (2) --O--C(O)--NHN(R 24 )(R 25 ) wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl or heterocyclic, each of which is optionally substituted with loweralkyl, hydroxy, aryl or heterocyclic and R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--,--NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and --NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--loweralkyl, (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic or (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group; R 9 is hydrogen; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

Claim 27

A compound according to claim 21 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 are defined as above; R 8 is defined as above; R 9 is hydrogen; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; R 20 is defined as above; R 24 is defined as above; and X and Y taken together are oxo.

Claim 28

A compound according to claim 21 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are (1) oxo, (2) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (3) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is --OC(O)N(OR 20 )(R 24 ) wherein R 20 and R 24 are defined as above; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 29

A compound according to claim 21 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are oxo; R 8 is --OC(O)N(OR 20 )(R 24 ) wherein R 20 is hydrogen, loweralkyl or arylalkyl and R 24 is hydrogen, loweralkyl or cycloalkyl; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 30

A compound according to claim 21 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are oxo; R 8 is --OC(O)N(OR 20 )(R 24 ) wherein R 20 is hydrogen, methyl or benzyl and R 24 is hydrogen or methyl; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 31

A compound of the formula: ##STR28## wherein R is F; R 1 is hydrogen, a hydroxy protecting group, loweralkyl or phenyl-substituted loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1)oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 9 is hydrogen; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

Claim 32

A compound of the formula: ##STR28## wherein R is F; R 1 is hydrogen, a hydroxy protecting group, loweralkyl or phenyl-substituted loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1)oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 9 is hydrogen; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

Claim 33

A compound according to claim 26 wherein R is F; R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 are defined as above; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 34

A compound according to claim 26 wherein R is F; R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are (1) oxo, (2) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (3) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 35

A compound according to claim 26 wherein R is F; R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are (1) oxo, (2) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (3) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 36

A compound according to claim 26 wherein R is F; R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are oxo; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 37

A compound of the formula: ##STR29## wherein R 1 is hydrogen, a hydroxy protecting group, loweralkyl or phenyl-substituted loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is (1) --O(CH 2 ) i C(O)OR 20 wherein i is one or two and R 20 is independently defined as above, (2) --O(CH 2 ) i C(O)N(R 24 )(R 25 ) wherein i is one or two and R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and--NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--loweralkyl, (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, (3) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (4) --O(CH 2 ) i C(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (5) --O(CH 2 ) i NHC(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (6) --(CH 2 ) i NHC(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above or (7) --(CH 2 ) i NHC(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above; R 9 is hydrogen; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

Claim 38

A compound of the formula: ##STR29## wherein R 1 is hydrogen, a hydroxy protecting group, loweralkyl or phenyl-substituted loweralkyl; R 2 is hydrogen and R 3 is hydroxy or protected hydroxy or R 2 and R 3 taken together are oxo; R 4 is hydrogen or phenyl-substituted loweralkyl and R 5 is hydroxy or protected hydroxy or R 5 is hydrogen or phenyl-substituted loweralkyl and R 4 is hydroxy or protected hydroxy or R 4 and R 5 taken together are oxo; R 6 is hydrogen or phenyl-substituted loweralkyl and R 7 is hydrogen, hydroxy or protected hydroxy or R 7 is hydrogen or phenyl-substituted loweralkyl and R 6 is hydroxy or protected hydroxy or R 6 and R 7 taken together are (1) oxo, (2) diazo, (3) ═CH 2 (4) --O--(CH 2 ) 2 --O--, (5) --S--(CH 2 ) 2 --S--, (6) --O--(CH 2 ) 3 --O--, (7) --S--(CH 2 ) 3 --S--, (8) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (9) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is (1) --O(CH 2 ) i C(O)OR 20 wherein i is one or two and R 20 is independently defined as above, (2) --O(CH 2 ) i C(O)N(R 24 )(R 25 ) wherein i is one or two and R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and--NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--loweralkyl, (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, (3) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (4) --O(CH 2 ) i C(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above, (5) --O(CH 2 ) i NHC(O)N(R 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, (6) --(CH 2 ) i NHC(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above or (7) --(CH 2 ) i NHC(O)N(R 24 )(N(R 24 )(R 25 )) wherein i, R 24 and R 25 are defined as above; R 9 is hydrogen; R 10a is hydrogen and R 10b is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10b is hydrogen and R 10a is hydrogen, hydroxy, protected hydroxy, alkoxy, alkenyl, alkenyloxy, halogen or --SR 28 wherein R 28 is independently defined as above or R 10a and R 10b are both alkoxy or --SR 28a wherein R 28a is loweralkyl, aryl or heterocyclic or R 10a and R 10b taken together are oxo; and X is hydrogen and Y is hydrogen, hydroxy or protected hydroxy or Y is hydrogen and X is hydroxy or protected hydroxy or X and Y taken together are oxo; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

Claim 39

A compound according to claim 31 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 are defined as above; R 8 is defined as above; R 9 is hydrogen; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 40

A compound according to claim 3 1 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 is hydrogen and R 5 is hydroxy or R 5 is hydrogen and R 4 is hydroxy or R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are (1) oxo, (2) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (3) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is (1) --O(CH 2 ) i C(O)N(R 24 )(R 25 ) wherein i is one or two and R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--; --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and--NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O-loweralkyl, (j) --NHC(O)-aryl, (k) --NHC(O)-heterocyclic and (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group or (2) --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i, R 24 and R 25 are defined as above, R 9 is hydrogen; R 10a is hydrogen, methoxy or fluoro and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 41

A compound according to claim 31 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are (1) oxo, (2) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (3) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is --O(CH 2 ) i C(O)N(R 24 )(R 25 ) wherein i is one or two and R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryl, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC(O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C (NR 27 )NHNH-- and--NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--loweralkyl, (j) --NHC(O)-aryl, (k)--NHC(O)-heterocyclic and (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, R 9 is hydrogen; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 42

A compound according to claim 31 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are (1) oxo, (2) ═N--OR 20 wherein R 20 is hydrogen, loweralkyl, alkenyl, cycloalkyl, cycloalkenyl, bicycloalkenyl, aryl, arylalkyl, heterocyclic or heterocyclicalkyl, each of which is optionally substituted with loweralkyl, halogen, hydroxy, aryl or heterocyclic; or (3) ═N--N(R 21 )(R 22 ) wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aryl, arylalkyl, heterocyclic and heterocyclicalkyl; R 8 is --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i is one or two and R 24 and R 25 are independently selected from (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkynyl, (e) cycloalkyl, (f) substituted loweralkyl, substituted alkenyl, substituted alkynyl or substituted cycloalkyl wherein the loweralkyl group, the alkenyl group, the alkynyl group or the cycloalkyl group is substituted by one or two substituents independently selected from (i) hydroxy, (ii) --COOH, (iii) --CN, (iv) --Q-loweralkyl, --Q-aryI, --Q-(arylalkyl), --Q-heterocyclic or --Q-(heterocyclicalkyl) wherein Q is --O--, --S--, --S(O)--, --S(O) 2 --, --C(O)--, --OC(O)--, --C(O)O--, --C(O)C(O)--O--, --O--C(O)C(O)--, --C(O)NH--, --NHC(O)--, --OC( O)NH--, --NHC(O)O--, --NH--C(O)--NH--, --S(O) 2 NH--, --NHS(O) 2 --, --N(R 27 )--, --C(NR 27 )NHNH-- and--NHNHC(NR 27 )-- wherein R 27 is hydrogen, loweralkyl, aryl or heterocyclic, (v) cycloalkyl, (vi) aryl, (vii) heterocyclic, (viii) --N(R 28 )(R 29 ) wherein R 28 and R 29 are independently selected from hydrogen, loweralkyl, hydroxyalkyl, aryl and heterocyclic, (ix) guanidino, (x) --S(O) 2 R 11 wherein R 11 is loweralkyl, aryl or arylalkyl, (xi) --OS(O) 2 R 11 wherein R 11 is defined as above, (xii) --SO 3 H, (xiii) --S(O) 2 NH 2 , (xiv) --SR 28 wherein R 28 is defined as above, (xv) halogen, (xvi) oxo and (xvii) epoxy; (g) aryl, (h) heterocyclic, (i) --NHC(O)--O--loweralkyl,. (j) --NHC(O)--aryl, (k) --NHC(O)--heterocyclic and (l) loweralkyl substituted by --OC(O)--R f wherein R f is carboxyalkyl or --N(R 24 )(R 25 ) taken together form a nitrogen-containing heterocyclic group, R 9 is hydrogen; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.

Claim 43

A compound according to claim 31 wherein R 1 is methyl; R 2 is hydrogen and R 3 is hydroxy; R 4 and R 5 taken together are oxo; R 6 and R 7 taken together are oxo; R 8 is --O(CH 2 ) i C(O)N(OR 24 )(R 25 ) wherein i is one or two and R 24 is hydrogen, loweralkyl or arylalkyl and R 25 is hydrogen, loweralkyl or cycloalkyl; R 9 is hydrogen; R 10a is methoxy and R 10b is hydrogen; and X and Y taken together are oxo.