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US 5,491,139 AGranted
Antimicrobial quinolonyl lactams
AssigneeThe Procter & Gamble Company
InventorsThomas P. Demuth, Jr., Ronald E. White
Life of this patent
Estimating the term…
Abstract
Antimicrobial quinolonyl lactam compounds comprising a lactam-containing moiety linked, by a non-ester linking moiety, 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 any of a variety of lactam-containing moieties similar to those known in the art to have antimicrobial activity; (2) A, R.sup.6, R.sup.7, and R.sup.8 form any of a variety of quinolone or naphthyridine structures similar to those known in the art to have antimicrobial activity; and (3) Y, together with R.sup.5, form a variety of non-ester linking moieties between the lactam-containing moiety and the quinolone moiety.
Claims35
A compound of the formula ##STR123## 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 having 1 or 2 heteroatoms selected from O, N, or S;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- 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;
- R.sup.10a --O--, R.sup.10a --O--, R.sup.10a CH=N--, (R.sup.10)(R.sup.11)N--, R.sup.12 --C(=CHR.sup.15)--C(=O)NH--, R.sup.12 --C(=NO--R.sup.14)--C(=O)NH--, or R.sup.13 --(CH.sub.2).sub.m --C(=O)NH--;
- where
- (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 heterocycle;
- or R.sup.10 and R.sup.11 together comprise 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 having 1 or 2 heteroatoms selected from O, N, or S;
- a 3-8 atom heteroalkenyl having 1 or 2 heteroatoms selected from O, N, or S;
- 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, or N;
- wherein said arylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group;
- and wherein said heteroarylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group having one or more heteroatoms selected from O, N, or S;
- (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, --(=O)O--R.sup.12, or --C(=O)NH--R.sup.12, where R.sup.17 and R.sup.18 are, independently, R.sup.12 or together comprise 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 heterocycles have one or more heteroatoms selected from O, S, or N;
- and
- wherein said arylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group;
- and wherein said heteroarylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group having one or more heteroatoms selected from O, N, or S;
- (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(=O)OR.sup.16, --C(=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 having 1 or 2 heteroatoms selected from O, N, or S;
- a 3-8 atom heteroalkenyl having 1 or 2 heteroatoms selected from O, N, or S;
- 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(=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 comprise 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
- (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 comprise 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 having of 1 or 2 heteroatoms selected from O, N, or S;
- a 3-8 atom heteroalkenyl having of 1 or 2 heteroatoms selected from O, N, or S;
- heteroarylalkyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- 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 wherein said arylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group and wherein said heteroarylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group having one or more heteroatoms selected from O, N, or S;
- 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 comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the nitrogen atom to which R.sup.19 is bonded;
- (B) R.sup.2 is hydrogen, halogen, alkoxy, or R.sup.22 C(=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) 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, or N;
- (E) X is X' or Z.sup.4 --R.sup.34 --X', where
- (a) Z.sup.4 is --O--;
- --S(O)t--, where t is an integer of 0 to 2;
- or --NR.sup.36 --;
- (b) X' is oxygen, sulfur, or R.sup.35 --NR.sup.36 ;
- (c) R.sup.34 is C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-8 atom heteroalkyl having 1 or 2 heteroatoms selected from O, N, or S;
- a 3-8 atom heteroalkenyl having 1 or 2 heteroatoms selected from O, N, or S;
- 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, or N;
- (d) R.sup.35 is nil, N(R.sup.36), or oxygen;
- (e) R.sup.36 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;
- wherein said heterocycles have one or more heteroatoms selected from O, S, or N;
- (F) (1) if X' is sulfur or R.sup.35 --NR.sup.36, Y is oxygen or Y';
- or
- (2) if X' is oxygen, Y is Y';
- where Y' is sulfur or --NR.sup.39 ;
- where R.sup.39 is hydrogen;
- C.sub.1 -C.sub.8 alkyl;
- oxygen;
- sulfur;
- or N(R.sup.10a);
- or if A.sup.3 is C(R.sup.41), then R.sup.39 and R.sup.41 may together comprise 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;
- (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;
- (5) R.sup.7 is hydrogen;
- halogen;
- alkyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- or a 3-9 atom monocycle or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or more heteroatoms selected from O, S, or N;
- and
- (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 comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- including N" and A.sup.1 ;
- wherein said heterocycles have 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 comprise --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 comprise 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 heterocycles have one or more heteroatoms selected from O, S, or N;
- and pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof.
135 more elements
A compound of the formula ##STR124## 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 having 1 or 2 heteroatoms selected from O, N, or S;
- 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=N--;
- (R.sup.10)(R.sup.11)N--;
- R.sup.12 --C(=CHR.sup.15)--C(=O)NH--;
- R.sup.12 --C(=NO--R.sup.14)--C(=O)NH--;
- or R.sup.13 --(CH.sub.2).sub.m --C(=O)NH--;
- wherein said heterocycles have one or two heteroatoms selected from O, S, or N;
- and where
- (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;
- or R.sup.10 and R.sup.11 together comprise 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 two 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 having 1 or 2 heteroatoms selected from O, N, or S;
- a 3-8 atom heteroalkenyl having 1 or 2 heteratoms selected from O, N, or S;
- 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 two 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(=O)O--R.sup.12 ;
- wherein said arylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group 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, N, or S;
- or --C(=O)NH--R.sup.12 ;
- where R.sup.17 and R.sup.18 are, independently, R.sup.12 or together comprise 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 heterocycles have one or two 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(=O)OR.sup.16, --C(=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 having 1 or 2 heteroatoms selected from O, N, or S;
- a 3-8 atom heteroalkenyl having 1 or 2 heteratoms selected from O, N, or S;
- 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(=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 comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or two heteroatoms selected from O, S, or N;
- and
- (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 comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or two 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 having 1 or 2 heteroatoms selected from O, N, or S;
- a 3-8 atom heteroalkenyl having 1 or 2 heteroatoms selected from O, N, or S;
- heteroarylalkyl;
- a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said arylalkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group 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, N, or S;
- amid wherein said heterocycles have one or two heteroatoms selected from O, S, or N;
- 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 comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the nitrogen atom to which R.sup.19 is bonded;
- and wherein said heterocycles have one or two heteroatoms selected from O, S, or N;
- (B) R.sup.2 is hydrogen, halogen, alkoxy, or R.sup.22 C(=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) X is X' or Z.sup.4 --R.sup.34 --X', where
- (1) Z.sup.4 is --O--;
- --S(O)t--, where t is an integer of 0 to 2;
- or --NR.sup.36 --;
- (2) X' is oxygen, sulfur, or R.sup.35 --NR.sup.36 ;
- (3) R.sup.34 is C.sub.1 -C.sub.8 alkyl;
- C.sub.2 -C.sub.8 alkenyl;
- a 3-8 atom heteroalkyl having 1 or 2 heteroatoms selected from O, N, or S;
- a 3-8 atom heteroalkenyl having 1 or 2 heteratoms selected from O, N, or S;
- 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 two heteroatoms selected from O, S, or N;
- (4) R.sup.35 is nil, N(R.sup.36), or oxygen;
- (5) R.sup.36 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;
- wherein said heterocycles have one or two heteroatoms selected from O, S, or N;
- (E) (1) if X' is sulfur or R.sup.35 --NR.sup.36, Y is oxygen or Y';
- or
- (2) if X' is oxygen, Y is Y';
- where Y' is sulfur or --NR.sup.39 ;
- where R.sup.39 is hydrogen, C.sub.1 -C.sub.8 alkyl, oxygen, sulfur, or N(R.sup.10a), or if A.sup.3 is C(R.sup.41), then R.sup.39 and R.sup.41 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or two heteroatoms selected from O, S, or N;
- (F) (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;
- aryl alkyl;
- or N(R.sup.10)(R.sup.11);
- wherein said aryl alkyl is a C.sub.1 -C.sub.8 alkyl substituted with an aryl group;
- and wherein said heterocycles have 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;
- and wherein said heterocycles have one or two heteroatoms selected from O, S, or N;
- (7) R.sup.9 is hydrogen, halogen, nitro, or N(R.sup.10)(R.sup.11);
- (G) except that
- (1) when A.sup.1 is C(R.sup.40), R.sup.8 and R.sup.40 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including N" and A.sup.1 ;
- wherein said heterocycles have one or two 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 comprise --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 comprise 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 heterocycles have one or two heteroatoms selected from O, S, or N;
- and pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof.
136 more elements
A compound of the formula ##STR125## wherein (A) R.sup.1 is C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.8 alkenyl, R.sup.12 --C(=NO--R.sup.14)--C(=O)NH--, or R.sup.13 --(CI.sub.2).sub.m --C(=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 a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- or R.sup.10 and R.sup.11 together comprise 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 two 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 heterocycles have one or two 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(=O)OR.sup.16, --C(=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 O;
- (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 having 1 or 2 heteroatoms selected from O, N, S;
- a 3-8 atom heteroalkenyl having 1 to 2 heteroatoms selected from O, N, or S;
- a 3.varies.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(=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 together may comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have 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 together may comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or two 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 heterocycles have one or two heteroatoms selected from O, S, or N;
- (B) R.sup.2 is hydrogen or alkoxy;
- (C) X is X' or Z.sup.4 --R.sup.34 --X', where
- (1) Z.sup.4 is --O--;
- --S(O)t--, where t is O;
- or --NR.sup.36 --;
- (2) X' is oxygen, sulfur, or R.sup.35 --NR.sup.36 ;
- (3) R.sup.34 is C.sub.1 -C.sub.8 alkyl or C.sub.2 -C.sub.8 alkenyl;
- (4) R.sup.35 is nil, N(R.sup.36), or oxygen;
- (5) R.sup.36 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;
- wherein said heterocycles have one or two heteroatoms selected from O, S, or N;
- (D) (1) if X' is sulfur or R.sup.35 --NR.sup.36, Y is oxygen;
- or
- (2) if X' is oxygen, Y is Y';
- where Y' is --NR.sup.39 ;
- where R.sup.39 is hydrogen, C.sub.1 -C.sub.8 alkyl, oxygen, sulfur, or N(R.sup.10a), or if A.sup.3 is C(R.sup.41), then R.sup.39 and R.sup.41 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or two heteroatoms selected from O, S, or N;
- (E) (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 wherein said heterocycles have one or two heteroatoms selected from O, S, or N;
- (7) R.sup.9 is hydrogen;
- (F) except that
- (1) when A.sup.1 is C(R.sup.40), R.sup.8 and R.sup.39 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including N" and A.sup.1 ;
- wherein said heterocycles have one or two 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 comprise --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 comprise 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 heterocycles have one or two heteroatoms selected from O, S, or N;
- and pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof.
76 more elements
Dependencies are inferred from the claim text.