US 6,387,928 B1Granted

Antimicrobial quinolones, their compositions and uses

AssigneeThe Procter & Gamble Company

InventorsBenoit Ledoussal, Ji-In Kim Almstead, Jeffrey Lyle Gray

Life of this patent

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Abstract

Compounds having the general structure: which are effective antimicrobial agents.

Claims18

Dependent claims

A compound having the following formula:

wherein:
(a) X is selected from the group consisting of
(b) R1 is selected from the group consisting of C3 to about C5 cycloalkyl, C1 to about C2 alkanyl, C2 to about C3 linear alkenyl, C3 to about C4 branched alkanyl or alkenyl, all such alkyl or cycloalkyl moieties being unsubstituted or substituted with from 1 to about 3 fluoro;
and phenyl, unsubstituted or substituted with from 1 to about 3 fluoro, or with one hydroxy in the 4-position;
(c) R3 is hydrogen or hydroxy;
(d) R5 is selected from the group consisting of hydrogen, hydroxy, amino, halo, C1 to about C2 alkanyl, C2 alkenyl, and methoxy, all such alkyl and methoxy moieties being unsubstituted or substituted with from 1 to about 3 fluoro;
(e) R8 is selected from the group consisting of fluoro, chloro and bromo;
(f) R7 is amino which is attached to a ring carbon of X which is not adjacent to the ring nitrogen, the amino being unsubstituted or substituted with one or two C1 to about C3 alkanyl;
or aminoalkanyl which is attached to any ring carbon of X and is C1 to about C3 alkanyl substituted with one amino, the amino being unsubstituted or substituted with one or two C1 to about C3 alkanyl;
(g) each R9 is independently selected from the group consisting of hydrogen, C1 to about C4 alkanyl, C2 to about C6 alkenyl or alkynyl, and a C3 to about C6 fused or spirocycle alkyl ring;
or one R9 may optionally be selected front the group consisting of hydroxy, C1 to about C4 alkoxy, aryl and heteroaryl, all other R9 being hydrogen;
all alkyl and aryl portions of R9 moieties being unsubstituted or substituted with one hydroxy or with from 1 to about 3 fluoro;
and
(h) a R7 moiety described in (f) and a R9 moiety described in (g) may optionally be connected thus forming a fused or spirocycle ring with the N-containing ring shown in (a), the fused or spirocycle ring comprising from 2 to about 5 ring carbons and 0 or 1 ring nitrogen;
or an optical isomer, diastereomer or enantiomer thereof;
a pharmaceutically-acceptable salt, hydrate, or biohydrolyzable ester, amide or imide thereof.

13 more elements

A compound &elected from the group consisting of:

7-[3R-(1S-aminoethylpyrrolidinyl)]-1-ethyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1S-aminoethylpyrrolidinyl)-1-(2-fluoroethyl)]-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1S-aminoethylpyrrolidinyl)]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1S-methylaminoethylpyrrolidinyl)]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1-amino-methylethylpyrrolidinyl)]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1-methylamino-methylethylpyrrolidinyl)]1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1S-aminoethyl-5-methyl-pyrrolidinyl)]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1S-aminoethyl-5,5-dimethyl-pyrrolidinyl)]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1-aminomethylethyl-5,5-dimethyl-pyrrolidinyl)]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1S-methylaminoethyl-5,5-dimethyl-pyrrolidinyl)]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1-methylaminomethylethyl-5,5-dimethyl-pyrrolidinyl)]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1S-aminoethyl-5-ethyl-pyrrolidinyl)]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1-aminomethylethyl-5-ethyl-pyrrolidinyl)]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1S-methylaminoethyl-5-ethyl-pyrrolidinyl)]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1-methylaminomethylethyl-5-ethyl-pyrrolidinyl)]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[3R-(1-amino-1-cyclopropyl-methylpyrrolidinyl)]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[6R-(1S-aminoethyl)-4-azaspiro[2.4]heptanyl]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[6R-(1S-methylaminoethyl)-4-azaspiro[2.4]heptanyl]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[6R-(1S-amino-methylethyl)-4-azaspiro[2.4]heptanyl]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-[6R-(1S-methylamino-methylethyl)-4-azaspiro[2.4]heptanyl]-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
or a pharmaceutically-acceptable salt thereof.

18 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/929,943Filed 15 Aug 2001 · continuation in part
Priority: 15 Sep 1997
Published: US 2002/0049192 A125 Apr 2002
Granted: 14 May 2002
Term ends: Not estimatedThe source records don’t support an estimate.

Classification2 codes

C07D 401/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
C07D
Heterocyclic compounds

Family

Application60/058,891Us provisional application · filed 15 Sep 1997
Application09/139,859Parent of this continuation-in-part · filed 25 Aug 1998
Application09/266,197Parent of this continuation-in-part · filed 10 Mar 1999
US 2002/0049192 A1Published application
US 6,329,391 B1Related patent
US 6,387,928 B1This patent

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

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A compound having the following formula:

wherein:
(a) X is selected from the group consisting of
(b) R1 is selected from the group consisting of C3 to about C5 cycloalkyl, C1 to about C2 alkanyl, C2 to about C3 linear alkenyl, C3 to about C4 branched alkanyl or alkenyl, all such alkyl or cycloalkyl moieties being unsubstituted or substituted with from 1 to about 3 fluoro;
and phenyl, unsubstituted or substituted with from 1 to about 3 fluoro, or with one hydroxy in the 4-position;
(c) R3 is hydrogen or hydroxy;
(d) R5 is selected from the group consisting of hydrogen, hydroxy, amino, halo, C1 to about C2 alkanyl, C2 alkenyl, and methoxy, all such alkyl and methoxy moieties being unsubstituted or substituted with from 1 to about 3 fluoro;
(e) R8 is selected from the group consisting of fluoro, chloro and bromo;
(f) R7 is amino which is attached to a ring carbon of X which is not adjacent to the ring nitrogen, the amino being unsubstituted or substituted with one or two C1 to about C3 alkanyl;
or aminoalkanyl which is attached to any ring carbon of X and is C1 to about C3 alkanyl substituted with one amino, the amino being unsubstituted or substituted with one or two C1 to about C3 alkanyl;
(g) each R9 is independently selected from the group consisting of hydrogen, C1 to about C4 alkanyl, C2 to about C6 alkenyl or alkynyl, and a C3 to about C6 fused or spirocycle alkyl ring;
or one R9 may optionally be selected front the group consisting of hydroxy, C1 to about C4 alkoxy, aryl and heteroaryl, all other R9 being hydrogen;
all alkyl and aryl portions of R9 moieties being unsubstituted or substituted with one hydroxy or with from 1 to about 3 fluoro;
and
(h) a R7 moiety described in (f) and a R9 moiety described in (g) may optionally be connected thus forming a fused or spirocycle ring with the N-containing ring shown in (a), the fused or spirocycle ring comprising from 2 to about 5 ring carbons and 0 or 1 ring nitrogen;
or an optical isomer, diastereomer or enantiomer thereof;
a pharmaceutically-acceptable salt, hydrate, or biohydrolyzable ester, amide or imide thereof.

13 more elements

Facts

Application

09/929,943Filed 15 Aug 2001 · continuation in part

Priority

15 Sep 1997

Published

US 2002/0049192 A125 Apr 2002

Granted

14 May 2002

Term ends

Not estimatedThe source records don’t support an estimate.

Classification2 codes

C07D 401/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
C07D
Heterocyclic compounds

Family

Application60/058,891Us provisional application · filed 15 Sep 1997

Application09/139,859Parent of this continuation-in-part · filed 25 Aug 1998

Application09/266,197Parent of this continuation-in-part · filed 10 Mar 1999

US 2002/0049192 A1Published application

US 6,329,391 B1Related patent

US 6,387,928 B1This patent

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