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US 5,180,719 AGranted
Antimicrobial quinolonyl lactam esters
AssigneeNorwich Eaton Pharmaceuticals, Inc.
InventorsRonald E. White, Thomas P. Demuth, Jr.
Life of this patent
Estimating the term…
Abstract
Antimicrobial quinolonyl lactam esters comprising a lactam-containing moiety linked, by an ester group, to the 3-carboxy group of a quinolone moiety. These compounds are of the formula: ##STR1## wherein (1) R.sup.3, R.sup.4, and R.sup.5, together with bonds "a" and "b", form certain lactam-containing moieties similar to those known in the art to have antimicrobial activity; and (2) A.sup.2, A.sup.2, A.sup.3, R.sup.7, R.sup.8, and R.sup.9 form any of a variety of quinolone or naphthyridine structures similar to those known in the art to have antimicrobial activity.
Claims29
A compound of the formula ##STR54## wherein (A) R.sup.1 is hydrogen;
- halogen;
- C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-8 atom heteroalkyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- R.sup.10a --O--;
- R.sup.10a CH.dbd.N--;
- (R.sup.10)(R.sup.11)N--;
- R.sup.12 --C(.dbd.CHR.sup.15)--C(.dbd.O)NH--;
- R.sup.12 --C(.dbd.NO--R.sup.14)--C(.dbd.O)NH--;
- or R.sup.13 --(CH.sub.2).sub.m --C(.dbd.O)NH--;
- wherein said heteroalkyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- and wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- (1) m is an integer from 0 to 9;
- (2) R.sup.10 and R.sup.11 are, independently, R.sup.10a where R.sup.10a is hydrogen;
- C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle or a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle substituent;
- or R.sup.10 and R.sup.11 together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the nitrogen to which they are bonded;
- wherein said heterocycles have one or more heteroatoms selected from O, S, or N;
- (3) R.sup.12 is hydrogen;
- C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-8 atom heteroalkyl;
- a 3-8 atom heteroalkenyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- or a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heteroalkyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- wherein said heteroalkenyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- and wherein said heterocycles have one or more heteroatoms selected from O, S, or N;
- (4) R.sup.13 is R.sup.12, --Z.sup.1, or --CH(Z.sup.2)(R.sup.12);
- (5) R.sup.14 is R.sup.12, arylalkyl, heteroarylalkyl, --C(R.sup.17)(R.sup.18)COOH, --C(.dbd.O)O--R.sup.12, or --C(.dbd.O)NH--R.sup.12, where R.sup.17 and R.sup.18 are, independently, R.sup.12, or together form a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle or a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the carbon atom to which R.sup.17 and R.sup.18 are bonded;
- wherein said arylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group substituted with one or two heteroatoms selected from O, S, or N;
- wherein said heteroarylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl which is substituted with one or two heteroatoms selected from O, S, or N;
- and wherein said heterocycles have one or more heteroatoms selected from O, S, or N;
- (6) R.sup.15 is R.sup.14, halogen, --Z.sup.1, or --CH(Z.sup.2)(R.sup.12);
- (7) Z.sup.1 is --C(.dbd.O)OR.sup.16, --C(.dbd.O)R.sup.16, --N(R.sup.19)R.sup.16, --S(O).sub.p R.sup.24, or --OR.sup.24 ;
- and Z.sup.2 is Z.sup.1 or --OH, --SH, or --SO.sub.3 H;
- (a) p is an integer from 0 to 2;
- (b) R.sup.19 is hydrogen;
- C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-8 atom heteroalkyl;
- a 3-8 member heteroalkenyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- --SO.sub.3 H;
- --C(.dbd.O)R.sup.20 ;
- or, when R.sup.13 is --CH(Z.sup.2)(R.sup.12) and Z.sup.2 is --N(R.sup.19)R.sup.16, R.sup.19 and R.sup.16 may together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or more heteroatoms selected from O, S, or N;
- wherein said heteroalkyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- and wherein said heteroalkenyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- (c) R.sup.20 is R.sup.12, NH(R.sup.12), N(R.sup.12)(R.sup.21), O(R.sup.21), or S(R.sup.21);
- where R.sup.21 is C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- or when R.sup.20 is N(R.sup.12)(R.sup.21), R.sup.21 and R.sup.12 may together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or more heteroatoms selected from O, S, or N;
- and
- (8) R.sup.16 is R.sup.24 or hydrogen;
- where R.sup.24 is C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- arylalkyl;
- a 3-8 atom heteroalkyl;
- a 3-8 atom heteroalkenyl;
- heteroarylalkyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- or, when Z.sup.1 is N(R.sup.19)R.sup.16 and R.sup.16 is R.sup.24, R.sup.16 and R.sup.19 may together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the nitrogen atom to which R.sup.19 is bonded;
- wherein said heterocycles have one or more heteroatoms selected from O, S, or N;
- wherein said arylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group substituted with one or two heteroatoms selected from O, S, or N;
- wherein said heteroalkyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- wherein said heteroalkenyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- and wherein said heteroarylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group substituted with one or more heteroatoms selected from O, S, or N;
- (B) R.sup.2 is hydrogen, halogen, alkoxy, or R.sup.22 C(.dbd.O)NH--, where R.sup.22 is hydrogen or C.sub.1 -C.sub.8 alkyl;
- (C) R.sup.28 is hydrogen or COOH;
- (D) s is an integer from 0 to 2;
- (E) R.sup.31 is nil, C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.8 alkenyl, a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- or a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or more heteroatoms selected from O, S, N;
- (F) Y is 0 or Z.sup.4 --R.sup.34 --O, where
- (1) Z.sup.4 is --O--;
- --S(O).sub.t --, where t is an integer of 0 to 2;
- or --NR.sup.10a --;
- (2) R.sup.34 is C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-8 atom heteroalkyl;
- a 3-8 atom heteroalkenyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- or a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- (G)
- (1) A.sup.1 is N or C(R.sup.40);
- where R.sup.40 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, C.sub.1 -C.sub.8 alkyl, or N(R.sup.10)(R.sup.11);
- (2) A.sup.2 is N or C(R.sup.6);
- where R.sup.6 is hydrogen or halogen;
- (3) A.sup.3 is N or C(R.sup.41);
- where R.sup.41 is hydrogen;
- (4) R.sup.8 is hydrogen;
- C.sub.1 -C.sub.8 alkyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- alkoxy;
- hydroxy;
- C.sub.2 -C.sub.8 alkenyl;
- arylalkyl;
- or N(R.sup.10)(R.sup.11);
- wherein said arylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group substituted with one or two heteroatoms selected from O, S, or N;
- and wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- (5) R.sup.7 is hydrogen, halogen, C.sub.1 -C.sub.8 alkyl, a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- or a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- (7) R.sup.9 is hydrogen, halogen, nitro, or N(R.sup.10)(R.sup.11);
- (H) except that
- (1) when A.sup.1 is C(R.sup.40), R.sup.8 and R.sup.40 may together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including N" and A.sup.1 ;
- wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- (2) when A.sup.2 is C(R.sup.6), R.sup.6 and R.sup.7 may together form --O--(CH.sub.2).sub.n --O--, where n is an integer from 1 to 4;
- and
- (3) when A.sup.3 is C(R.sup.41), R.sup.8 and R.sup.41 may together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including N" and the adjacent carbon to which R.sup.41 is bonded;
- wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- and pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof.
120 more elements
A compound of the formula ##STR55## wherein (A) R.sup.1 is hydrogen;
- halogen;
- C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-8 atom heteroalkyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- R.sup.10a --O--;
- R.sup.10a CH.dbd.N--;
- (R.sup.10)(R.sup.11)N--;
- R.sup.12 --C(.dbd.CHR.sup.15)--C(.dbd.O)NH--;
- R.sup.12 --C(.dbd.NO--R.sup.14)--C(.dbd.O)NH--;
- or R.sup.13 --(CH.sub.2).sub.m --C(.dbd.O)NH--;
- wherein said heteroalkyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- and wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- (1) m is an integer from 0 to 9;
- (2) R.sup.10 and R.sup.11 are, independently, R.sup.10a where R.sup.10a is hydrogen;
- C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle or a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle substituent;
- wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- or R.sup.10 and R.sup.11 together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the nitrogen to which they are bonded;
- wherein said heterocycles have one or more heteroatoms selected from O, S, or N;
- (3) R.sup.12 is hydrogen;
- C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-8 atom heteroalkyl;
- a 3-8 atom heteroalkenyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- or a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heteroalkyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- wherein said heteroalkenyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- and wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- (4) R.sup.13 is R.sup.12, --Z.sup.1, or --CH(Z.sup.2)(R.sup.12);
- (5) R.sup.14 is R.sup.12, arylalkyl, heteroarylalkyl, --C(R.sup.17)(R.sup.18)COOH, --C(.dbd.O)O--R.sup.12, or --C(.dbd.O)NH--R.sup.12, where R.sup.17 and R.sup.18 are, independently, R.sup.12, or together form a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle or a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the carbon atom to which R.sup.17 and R.sup.18 are bonded;
- wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- wherein said arylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group substituted with one or two heteroatoms selected from O, S, or N;
- and wherein said heteroarylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group substituted with one or more heteroatoms selected from O, S, or N;
- (6) R.sup.15 is R.sup.14, halogen, --Z.sup.1, or --CH(Z.sup.2)(R.sup.12);
- (7) Z.sup.1 is --C(.dbd.O)OR.sup.16, --C(.dbd.O)R.sup.16, --N(R.sup.19)R.sup.16, --S(O).sub.p R.sup.24, or --OR.sup.24 ;
- and Z.sup.2 is Z.sup.1 or --OH, --SH, or --SO.sub.3 H;
- (a) p is an integer from 0 to 2;
- (b) R.sup.19 is hydrogen;
- C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-8 atom heteroalkyl;
- a 3-8 atom heteroalkenyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- --SO.sub.3 H;
- --C(.dbd.O)R.sup.20 ;
- or, when R.sup.13 is --CH(Z.sup.2)(R.sup.12) and Z.sup.2 is --N(R.sup.19)R.sup.16, R.sup.19 and R.sup.16 form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- wherein said heteroalkyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- and wherein said heteroalkenyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- (c) R.sup.20 is R.sup.12, NH(R.sup.12), N(R.sup.12)(R.sup.21), O(R.sup.21), or S(R.sup.21);
- where R.sup.21 is C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- or when R.sup.20 is N(R.sup.12)(R.sup.21), R.sup.21 and R.sup.12 may together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or more heteroatoms selected from O, S, or N;
- (8) R.sup.16 is R.sup.24 or hydrogen;
- where R.sup.24 is C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- arylalkyl;
- a 3-8 atom heteroalkyl;
- a 3-8 atom heteroalkenyl;
- heteroarylalkyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- or, when Z.sup.1 is N(R.sup.19)R.sup.16 is R.sup.24, R.sup.16 and R.sup.19 may together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the nitrogen atom to which R.sup.19 is bonded;
- wherein said arylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group;
- wherein said heteroalkyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- wherein said heteroarylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group substituted with one or two heterocarbons selected from O, S, or N;
- wherein said heteroalkenyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- and wherein said heterocycles have one or more heteroatoms selected from O, S, or N;
- (B) R.sup.2 is hydrogen, halogen, alkoxy, or R.sup.22 C(.dbd.O)NH--, where R.sup.22 is hydrogen or C.sub.1 -C.sub.8 alkyl;
- (C) s is an integer from 0 to 2;
- (D)
- (1) A.sup.1 is N or C(R.sup.40);
- where R.sup.40 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, C.sub.1 -C.sub.8 alkyl, or N(R.sup.10)(R.sup.11);
- (2) A.sup.2 is N or C(R.sup.6);
- where R.sup.6 is hydrogen or halogen;
- (3) A.sup.3 is N or C(R.sup.41);
- where R.sup.41 is hydrogen;
- (4) R.sup.8 is hydrogen;
- C.sub.1 -C.sub.8 alkyl;
- a 3-9 monocyclic or 7-17 atom polycyclic carbocycle;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- alkoxy;
- hydroxy;
- C.sub.2 -C.sub.8 alkenyl;
- arylalkyl;
- or N(R.sup.10)(R.sup.11);
- wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- and wherein said arylalkyl is a C.sub.1 -C.sub.8 alkyl with an aryl substituent;
- (5) R.sup.7 is hydrogen, halogen, C.sub.1 -C.sub.8 alkyl, a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- or a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- and
- (7) R.sup.9 is hydrogen, halogen, nitro, or N(R.sup.10)(R.sup.11);
- (E) except that
- (1) when A.sup.1 is C(R.sup.40), R.sup.8 and R.sup.40 may together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including N" and A.sup.1 ;
- wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- (2) when A.sup.2 is C(R.sup.6), R.sup.6 and R.sup.7 may together form --O--(CH.sub.2).sub.n --O--, where n is an integer from 1 to 4;
- and
- (3) when A.sup.3 is C(R.sup.41), R.sup.8 and R.sup.41 may together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including N" and the adjacent carbon to which R.sup.41 is bonded;
- and pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof.
104 more elements
A compound of the formula ##STR56## wherein (A) R.sup.1 is C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- R.sup.12 --C(.dbd.NO--R.sup.14)--C(.dbd.O)NH--, or R.sup.13 --(CH.sub.2).sub.m --C(.dbd.O)NH--;
- where
- (1) m is an integer from 0 to 3;
- (2) R.sup.10 and R.sup.11 are, independently, R.sup.10a where R.sup.10a is hydrogen;
- C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle, or 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle substituents;
- or R.sup.10 and R.sup.11 together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the nitrogen to which they are bonded;
- wherein said heterocycles have one or more heteroatoms selected from O, S, or N;
- (3) R.sup.12 is C.sub.1 -C.sub.8 alkyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- or a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- (4) R.sup.13 is R.sup.12, --Z.sup.1, or --CH(Z.sup.2)(R.sup.12);
- (5) R.sup.14 is R.sup.12 or --C(R.sup.17)(R.sup.18)COOH);
- (6) R.sup.15 is R.sup.14 or halogen;
- (7) Z.sup.1 is --C(.dbd.O)OR.sup.16, --C(.dbd.O)R.sup.16), --N(R.sup.19)R.sup.16, --S(O).sub.p R.sup.24, or --OR.sup.24 ;
- and Z.sup.2 is Z.sup.1 or --OH, --SH, or --SO.sub.3 H;
- (a) p is 0;
- (b) R.sup.19 is hydrogen;
- C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-8 atom heteroalkyl;
- a 3-8 atom heteroalkenyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- --SO.sub.3 H;
- --C(.dbd.O)R.sup.20 ;
- or, when R.sup.13 is --CH(Z.sup.2)(R.sup.12) and Z.sup.2 is --N(R.sup.19)R.sup.16, R.sup.19 and R.sup.16 may together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heteroalkyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- and wherein said heteroalkenyl has carbon atoms and one or two heteroatoms selected from O, S, or N;
- (c) R.sup.20 is R.sup.12, NH(R.sup.12), N(R.sup.12)(R.sup.21);
- where R.sup.21 is C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- or when R.sup.20 is N(R.sup.12)(R.sup.21), R.sup.21 and R.sup.12 may together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or more heteroatoms selected from O, S, or N;
- (8) R.sup.16 is hydrogen;
- C.sub.1 -C.sub.8 alkyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- or a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- (B) R.sup.2 is hydrogen or alkoxy;
- (C)
- (1) A.sup.1 is N or C(R.sup.40);
- where R.sup.40 is hydrogen or halogen;
- (2) A.sup.2 is C(R.sup.6);
- where R.sup.6 is hydrogen or halogen;
- (3) A.sup.3 is C(R.sup.41);
- where R.sup.41 is hydrogen;
- (4) R.sup.8 is C.sub.1 -C.sub.8 alkyl or a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- (5) R.sup.7 is a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- and
- (6) R.sup.9 is hydrogen;
- (D) except that
- (1) when A.sup.1 is C(R.sup.40), R.sup.8 and R.sup.39 may together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including N" and A.sup.1 ;
- wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- (2) when A.sup.2 is C(R.sup.6), R.sup.6 and R.sup.7 may together form --O--(CH.sub.2).sub.n --O--, where n is an integer from 1 to 4;
- and
- (3) when A.sup.3 is C(R.sup.41), R.sup.8 and R.sup.41 may together form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including N" and the adjacent carbon to which R.sup.41 is bonded;
- wherein said heterocycle has one or more heteroatoms selected from O, S, or N;
- and pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof.
61 more elements
Dependencies are inferred from the claim text.