US 5,672,600 AGranted

Antimicrobial dithiocarbamoyl quinolones

AssigneeThe Procter & Gamble Company

InventorsThomas Prosser Demuth, Jr., Ronald Eugene White

Life of this patent

Estimating the term…

Abstract

Antimicrobial dithiocarbamoyl quinolone 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 dithiocarbamate containing moiety; and pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof.

Claims33

Dependent claims

A dithiocarbamate-containing compound having one of the following structures:

##STR55## wherein (A)
(1) X is the dithiocarbamate-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)
(1) 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 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
and
(2) 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;
a 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
or
(3) when X is R.sup.15 --N(R.sup.16)(R.sup.17), R.sup.16 and R.sup.15 may together comprise a 4-9 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)--S--M, where M is a pharmaceutically-acceptable salt or biohydrolyzable ester;
and
(c)
(1) R.sup.18 is C.sub.1 -C.sub.8 alkyl;
a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
or a 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
and
(2) 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;
or a 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
or
(3) R.sup.18 and R.sup.19 may together comprise a 4-9 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
(i) R.sup.7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, C.sub.1 -C.sub.8 alkyl, or N(R.sup.8)(R.sup.9), and
(ii) 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 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
or R.sup.8 and R.sup.9 together comprise a 4-9 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 N or C(R.sup.2);
where R.sup.2 is hydrogen or halogen;
(4) A.sup.3 is N or C(R.sup.5);
where R.sup.5 is hydrogen;
(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 4-9 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 4-9 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, halogen, nitro or N(R.sup.8)(R.sup.9);
(B) and where
(1) when A.sup.1 is C(R.sup.7), R.sup.1 and R.sup.7 may together comprise a 4-9 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.2 is C(R.sup.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 4-9 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 4-9 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
(C) provided that only one of A.sup.1, A.sup.2, or A.sup.3 is N;
and pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof.

78 more elements

A dithiocarbamate-containing compound having the following structure:

##STR56## wherein (A)
(1) X is the dithiocarbamate-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)
(1) 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 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
and
(2) 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 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
or
(3) when X is R.sup.15 --N(R.sup.16)(R.sup.17), R.sup.16 and R.sup.15 may together comprise a 4-9 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)--S--M, where M is a pharmaceutically-acceptable salt or biohydrolyzable ester;
and
(c)
(1) R.sup.18 is C.sub.1 -C.sub.8 alkyl;
a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
or a 4-9 atom monocyclic or 7-17 atom polycyclic hetero cycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
and
(2) 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;
or a 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
or
(3) R.sup.18 and R.sup.19 may together comprise a 4-9 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 hydrogen or halogen;
(4) A.sup.3 is C(R.sup.5);
where R.sup.5 is hydrogen;
(5) R.sup.1 is C.sub.1 -C.sub.8 alkyl;
aryl;
cycloalkyl;
or alkylamino;
(6) R.sup.4 is hydroxy;
and
(7) R.sup.6 is hydrogen, halogen, nitro or N(R.sup.8)(R.sup.9);
(B) and where R.sup.4 and R.sup.5 may together comprise a 4-9 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 pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof.

47 more elements

A dithiocarbamate-containing compound having one of the following structures:

##STR57## wherein (A)
(1) X is the dithiocarbamate-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)
(1) 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 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
and
(2) 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 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
or
(3) when X is R.sup.15 --N(R.sup.16)(R.sup.17), R.sup.16 and R.sup.15 may together comprise a 4-9 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)--S--M, where M is a pharmaceutically-acceptable salt or biohydrolyzable ester;
and
(c)
(1) R.sup.18 is C.sub.1 -C.sub.8 alkyl;
a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
or a 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
and
(2) 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;
or a 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
or
(3) R.sup.18 and R.sup.19 may together comprise a 4-9 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 C.sub.1 -C.sub.8 alkyl or a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
(6) R.sup.3 is a 4-9 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;
and
(2) R.sup.4 and R.sup.5 may together comprise a 4-9 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 pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof.

49 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/327,063Filed 21 Oct 1994 · division
Priority: 24 Oct 1988
Granted: 30 Sep 1997
Term ends: Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07D 401/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
C07D 215/56
Attached in position 3: with oxygen atoms in position 4
C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links

Family

Serial261,948Parent of this continuation-in-part · filed 24 Oct 1988
Serial418,029Parent of this continuation · filed 12 Oct 1989
Serial696,985Parent of this division · filed 2 May 1991
US 5,387,748 AParent of this division
US 5,672,600 AThis patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A dithiocarbamate-containing compound having one of the following structures:

##STR55## wherein (A)
(1) X is the dithiocarbamate-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)
(1) 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 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
and
(2) 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;
a 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
or
(3) when X is R.sup.15 --N(R.sup.16)(R.sup.17), R.sup.16 and R.sup.15 may together comprise a 4-9 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)--S--M, where M is a pharmaceutically-acceptable salt or biohydrolyzable ester;
and
(c)
(1) R.sup.18 is C.sub.1 -C.sub.8 alkyl;
a 3-9 atom monocyclic or 7-17 atom polycyclic carbocycle;
or a 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
and
(2) 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;
or a 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
wherein said heterocycles have one or more heteroatoms chosen from O, S, or N;
or
(3) R.sup.18 and R.sup.19 may together comprise a 4-9 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
(i) R.sup.7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, C.sub.1 -C.sub.8 alkyl, or N(R.sup.8)(R.sup.9), and
(ii) 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 4-9 atom monocyclic or 7-17 atom polycyclic heterocycle;
or R.sup.8 and R.sup.9 together comprise a 4-9 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 N or C(R.sup.2);
where R.sup.2 is hydrogen or halogen;
(4) A.sup.3 is N or C(R.sup.5);
where R.sup.5 is hydrogen;
(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 4-9 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 4-9 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, halogen, nitro or N(R.sup.8)(R.sup.9);
(B) and where
(1) when A.sup.1 is C(R.sup.7), R.sup.1 and R.sup.7 may together comprise a 4-9 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.2 is C(R.sup.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 4-9 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 4-9 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
(C) provided that only one of A.sup.1, A.sup.2, or A.sup.3 is N;
and pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof.

78 more elements

Facts

Application

08/327,063Filed 21 Oct 1994 · division

Priority

24 Oct 1988

Granted

30 Sep 1997

Term ends

Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07D 401/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
C07D 215/56
Attached in position 3: with oxygen atoms in position 4
C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links

Family

Serial261,948Parent of this continuation-in-part · filed 24 Oct 1988

Serial418,029Parent of this continuation · filed 12 Oct 1989

Serial696,985Parent of this division · filed 2 May 1991

US 5,387,748 AParent of this division

US 5,672,600 AThis patent

From the US filing history. Foreign family members aren’t listed.