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US 5,631,256 AGranted
Antimicrobial quinolone thioureas
AssigneeThe Procter & Gamble Company
InventorsThomas P. Demuth, Jr., Ronald E. White
Life of this patent
Estimating the term…
Abstract
Antimicrobial quinolone thiourea compounds of the general formula: ##STR1## wherein (1) A.sup.1, A.sup.2, A.sup.3, R.sup.1, R.sup.3, R.sup.4, and R.sup.6 form any of a variety of quinolone and related heterocyclic structures similar to those known in the art to have antimicrobial activity; and (2) (1) R.sup.1 is X, R.sup.3 is X, or both R.sup.1 and R.sup.3 are X; and X is the thiourea containing moiety and pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof.
Claims29
Thiourea-containing compounds having one of the following structures:
- ##STR12## wherein (A)
- (1) X is the thiourea-containing moiety --R.sup.15 --N(R.sup.16)(R.sup.17) or --R.sup.15 --R.sup.18 --N(R.sup.19)(R.sup.17), where
- (a)
- (i) R.sup.15 is nil;
- 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 more heteroatoms chosen from O, S, or N;
- and
- (ii) R.sup.16 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 chosen from O, S, or N;
- or
- (iii) when X is R.sup.15 --N(R.sup.16)(R.sup.17), R.sup.16 and R.sup.15 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the nitrogen atom to which R.sup.15 and R.sup.16 are bonded;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- (b) R.sup.17 is --C(.dbd.S)--NR.sup.20 R.sup.21 ;
- where R.sup.20 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 chosen from O, S, or N;
- and R.sup.21 is R.sup.20 or N(R.sup.20)(R.sup.20);
- or R.sup.20 and R.sup.21, together with the nitrogen to which they are bonded, form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- and
- (c)
- (i) R.sup.18 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 more heteroatoms chosen from O, S, or N;
- and
- (ii) R.sup.19 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;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- or
- (iii) K.sup.18 and K.sup.19 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the nitrogen atom to which K.sup.18 and K.sup.19 are bonded;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- (2) A.sup.1 is N or C(R.sup.7);
- where
- (a) R.sup.7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, C.sub.1 -C.sub.8 alkyl, or N(R.sup.5)(R.sup.9), and
- (b) R.sup.8 and R.sup.9 are, independently, R.sup.8a ;
- where R.sup.8a 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.8 and R.sup.9 together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle that includes the nitrogen atom to which they are bonded;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- (3) A.sup.2 is C(R.sup.2);
- where R.sup.2 is hydrogen or halogen;
- (4)
- (a) when A.sup.1 is N, A.sup.3 is N or C(R.sup.5), where R.sup.5 is hydrogen;
- and
- (b) when A.sup.1 is C(R.sup.7), A.sup.3 is N;
- (5) R.sup.1 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.8)(R.sup.9);
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- (6) R.sup.3 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 heterocycles have one or more heteroatoms chosen from O, S, or N;
- (7) R.sup.4 is hydroxy;
- and
- (8) R.sup.6 is hydrogen, C.sub.1 -C.sub.8 alkyl, halogen, nitro, N(R.sup.8)(R.sup.9), or S(R.sup.8a);
- (B) and where
- (1) when A.sup.1 is C(R.sup.7), R.sup.1 and R.sup.7 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 chosen from O, S, or N;
- (2) R.sup.2 and R.sup.3 may together comprise --O--(CH.sub.2).sub.n --O--, where n is from 1 to 4;
- (3) when A.sup.3 is C(R.sup.5), R.sup.4 and R.sup.5 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the carbon atoms to which R.sup.4 and R.sup.5 are bonded and the carbon atom to which said carbon atoms are bonded;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- and
- (4) when A.sup.3 is C(R.sup.5), R.sup.1 and R.sup.5 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including N' and the adjacent carbon to which R.sup.5 is bonded;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- and pharmaceutically-acceptable salts, biohydrolyzable esters, and hydrates thereof.
87 more elements
Thiourea-containing compounds having the following structure:
- ##STR13## wherein (A)
- (1) X is the thiourea-containing moiety --R.sup.15 --N(R.sup.16)(R.sup.17) or --R.sup.15 --R.sup.18 --N(R.sup.19)(R.sup.17), where
- (a)
- (i) R.sup.15 is nil;
- 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 more heteroatoms chosen from O, S, or N;
- and
- (ii) R.sup.16 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 chosen from O, S, or N;
- or
- (iii) when X is R.sup.15 --N(R.sup.16)(R.sup.17), R.sup.16 and R.sup.15 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the nitrogen atom to which R.sup.15 and R.sup.16 are bonded;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- (b) R.sup.17 is --C(.dbd.S)--NR.sup.20 R.sup.21 ;
- where R.sup.20 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 chosen from O, S, or N;
- and R.sup.21 is R.sup.20 or N(R.sup.20)(R.sup.20);
- or R.sup.20 and R.sup.21, together with the nitrogen to which they are bonded, form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- and
- (c)
- (i) R.sup.18 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 more heteroatoms chosen from O, S, or N;
- and
- (ii) R.sup.19 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;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- or
- (iii) R.sup.18 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.18 and R.sup.19 are bonded;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- (2) A.sup.1 is N or C(R.sup.7);
- where R.sup.7 is hydrogen or halogen;
- (3) A.sup.2 is C(R.sup.2);
- where R.sup.2 is hydrogen or halogen;
- (4)
- (a) when A.sup.1 is N, A.sup.3 is N or C(R.sup.5), where R.sup.5 is hydrogen;
- and
- (b) when A.sup.1 is C(R.sup.7), A.sup.3 is N;
- (5) R.sup.1 is C.sub.1 -C.sub.8 alkyl, a 3-9 atom monocyclic or 7-17 atom polycyclic aryl, a 3-9 atom monocyclic or 7-17 atom polycyclic cycloalkyl, or alkylamino;
- (6) R.sup.4 is hydroxy;
- and
- (7) R.sup.6 is hydrogen, C.sub.1 -C.sub.8 alkyl, halogen, nitro, N(R.sup.8)(R.sup.9), or S(R.sup.8a);
- (B) and where
- (1) when A.sup.1 is C(R.sup.7), R.sup.1 and R.sup.7 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 chosen from O, S, or N;
- (2) when A.sup.3 is C(R.sup.5), R.sup.4 and R.sup.5 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the carbon atoms to which R.sup.4 and R.sup.5 are bonded and the carbon atom to which said carbon atoms are bonded;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- and
- (3) when A.sup.3 is C(R.sup.5), R.sup.1 and R.sup.5 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including N' and the adjacent carbon to which R.sup.5 is bonded;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- and pharmaceutically-acceptable salts, biohydrolyzable esters, and hydrates thereof.
62 more elements
Thiourea-containing compounds having one of the following structures:
- ##STR14## wherein (A)
- (1) X is the thiourea-containing moiety --R.sup.15 --N(R.sup.16)(R.sup.17) or --R.sup.15 --R.sup.18 --N(R.sup.19)(R.sup.17), where
- (a)
- (i) R.sup.15 is nil;
- 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 more heteroatoms chosen from O, S, or N;
- and
- (ii) R.sup.16 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 chosen from O, S, or N;
- or
- (iii) when X is R.sup.15 --N(R.sup.16)(R.sup.17), R.sup.16 and R.sup.15 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the nitrogen atom to which R.sup.15 and R.sup.16 are bonded;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- (b) R.sup.17 is --C(.dbd.S)--NR.sup.20 R.sup.21 ;
- where R.sup.20 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 chosen from O, S, or N;
- and R.sup.21 is R.sup.20 or N(R.sup.20)(R.sup.20);
- or R.sup.20 and R.sup.21, together with the nitrogen to which they are bonded, form a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- and
- (c)
- (i) R.sup.18 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 more heteroatoms chosen from O, S, or N;
- and
- (ii) R.sup.19 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;
- a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- or
- (iii) R.sup.18 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.18 and R.sup.19 are bonded;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- (2) A.sup.1 is N;
- (3) A.sup.2 is C(R.sup.2);
- where R.sup.2 is halogen;
- (4) A.sup.3 is C(R.sup.5);
- where R.sup.5 is hydrogen;
- (5) R.sup.1 is alkyl;
- or a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
- (6) R.sup.3 is a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- (7) R.sup.4 is hydroxy;
- and
- (8) R.sup.6 is hydrogen;
- (B) and where
- (1) R.sup.2 and R.sup.3 may together comprise --O--(CH.sub.2).sub.n --O--, where n is from 1 to 4;
- (2) R.sup.4 and R.sup.5 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including the carbon atoms to which R.sup.4 and R.sup.5 are bonded and the carbon atom to which said carbon atoms are bonded;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- and
- (3) R.sup.1 and R.sup.5 may together comprise a 3-9 atom monocyclic or 7-17 atom polycyclic heterocycle including N' and the adjacent carbon to which R.sup.5 is bonded;
- wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
- and pharmaceutically-acceptable salts, biohydrolyzable esters, and hydrates thereof.
61 more elements
Dependencies are inferred from the claim text.