US 2009/0156577 A1Published application

7-amino alkylidenyl-heterocyclic quinolones and naphthyridones

OwnerBenjamin Davis, Eugene B. Grant, III +6inventors

InventorsBenjamin Davis, Eugene B. Grant, III, Shu-Chen Lin, Mark J. Macielag, Michele Ann Weidner-Wells, Xiaoqing Xu, Xiaodong Xu, Bin Zhu

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Abstract

The present invention relates to compounds having a structure according to Formula (I) wherein n, m, z, R, R2, R3, R4, R5, R6, A, E, X, Y, a and b are as defined above; or an optical isomer, diastereomer or enantiomer thereof; a pharmaceutically acceptable salt, hydrate, or prodrug thereof.

Claims24

Dependent claims

A compound having a structure according to Formula (I):

wherein:
n is an integer from 1 to 3;
m is an integer from 1 to 3;
z is an integer from 0 to 3;
R is selected from hydrogen, hydroxy, and alkoxy;
R2 is hydrogen;
R3 and R4 are independently selected from hydrogen, halogen, amino, hydroxy, alkoxy, alkylthio, alkyl, alkenyl and alkynyl;
R5 is selected from hydrogen, hydroxy, halogen, alkyl, aryl, alkoxy, cyano, CO2R13, and alkylthio;
R6 is independently selected from alkyl, hydroxy, alkoxy, alkylthio, alkenyl, alkynyl, aryl, alkoxyimino, and halogen;
or R5 and R6 join to form a 4- to 7-membered carbocyclic ring wherein each carbon atom of the ring can be optionally substituted with R12, wherein R12 is selected from the group consisting of halogen, amino, hydroxy, alkoxy, alkylthio, alkyl, alkenyl, alkynyl, oxo, alkoxyimino and hydroxyimino;
R13 is hydrogen, alkyl, aryl, or a carboxylic acid protecting group;
E is selected from the group consisting of:
wherein,
q is an integer from 1 to 3;
In the case of 1), R7 and R8 are each independently selected from hydrogen and alkyl, or R7 and R8 join to form a 3 to 6 membered carbocyclic ring, or either of R7 or R8 can be joined independently to either of R9 or R10 to form a heterocyclic ring containing the nitrogen atom to which R9 or R10 are bonded, wherein
R9 and R10 are each independently selected from hydrogen, alkyl, aryl, arylalkyl, acyl, alkoxycarbonyl, or sulfonyl, or alternatively R9 and R10 join to form a heterocyclic ring containing the nitrogen atom to which they are bonded;
In the case of 2), R7 and R8 are each independently selected from hydrogen and alkyl, or R7 and R8 join to form a 3- to 6-membered carbocyclic ring, and R9 is selected from hydrogen, alkyl, acyl, alkoxycarbonyl, or sulfonyl;
A is selected from N and C(R11), wherein R11 is selected from hydrogen, alkyl, halogen, hydroxy, alkoxy, alkylthio or cyano;
X is selected from C and N, where if X is C, then a is a double bond and b is a single bond, and if X is N, then a is a single bond and b is a double bond;
and
Y is selected from N(R1) and C(R1), with the proviso that when Y is N(R1), then X is C and when Y is C(R1), then X is N;
wherein
R1 is selected from C3 to C6 cycloalkyl, C4 to C6 heterocycloalkyl, alkyl, alkene, a 6-membered aryl and a 6-membered heteroaryl;
provided that
if A is C(R11), X is C and Y is N(R1), then R11 and R1 can join to form a 6-membered heterocyclic ring optionally substituted by one or more alkyl groups for a corresponding hydrogen atom;
or
if A is C(R11), X is C and Y is N(R1), then R2 and R1 can join to form a monocyclic or bicyclic heterocyclic ring optionally substituted by one or more alkyl groups for a corresponding hydrogen atom;
or
if A is C(R11), X is C and Y is N(R1), then R2 and R can join to form a 5-membered heterocyclic ring optionally substituted by one or more alkyl groups for a corresponding hydrogen atom;
or an optical isomer, diastereomer or enantiomer thereof or a pharmaceutically acceptable salt, hydrate, or prodrug thereof.

27 more elements

A compound having a structure according to Formula (Ia):

wherein:
R is selected from hydrogen, hydroxy or alkoxy;
R2 is selected from the group consisting of:
n is an integer selected from 1, 2 or 3;
m is an integer selected from 1, 2 or 3;
z is an integer selected from 0, 1, 2 or 3;
R3 and R4 are independently selected from hydrogen, halogen, amino, hydroxy, alkoxy, alkylthio, alkyl, alkenyl or alkynyl;
R5 is selected from hydrogen, halogen, alkyl, aryl, alkoxy, cyano, CO2R13 or alkylthio;
R6 is independently selected from alkyl, hydroxy, alkoxy, alkylthio, alkenyl, alkynyl, aryl, alkoxyimino or halogen, wherein alkyl is optionally mono- or disubstituted on an R2 carbon atom;
alternatively, R5 and R6 join to form a 4- to 7-membered carbocyclic ring wherein each carbon atom of the ring can be optionally substituted with R12;
R12 is selected from the group consisting of halogen, amino, hydroxy, alkoxy, alkylthio, alkyl, alkenyl, alkynyl, oxo, alkoxyimino and hydroxyimino;
R13 is hydrogen, alkyl, aryl, or a protecting group;
E is selected from the group consisting of:
wherein,
q is an integer selected from 1, 2 or 3;
R7 and R8 are each independently selected from hydrogen or alkyl;
alternatively, R7 and R8 join to form a 3- to 6-membered carbocyclic ring;
alternatively, either of R7 or R8 can be joined independently to either of R9 or R10 to form a heterocyclic ring containing the nitrogen atom to which R9 or R10 are bonded;
R9 and R10 are each independently selected from hydrogen, alkyl, acyl, aminoacetyl, arylalkyl, alkoxycarbonyl or sulfonyl;
alternatively, R9 and R10 can be joined to form a heterocyclic ring containing the nitrogen atom to which they are bonded, wherein the heterocyclic ring is optionally substituted on one or two carbon atoms with oxo;
R16 is selected from hydrogen, alkyl, acyl, alkoxycarbonyl or sulfonyl;
A is selected from N and C(R11);
R11 is selected from hydrogen, alkyl, haloalkyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio or cyano;
X is selected from C and N, wherein if X is C, then a is a double bond and b is a single bond, and if X is N, then a is a single bond and b is a double bond;
Y is selected from N(R1) and C(R1), with the proviso that when Y is N(R1), then X is C and when Y is C(R1), then X is N;
R1 is selected from an optionally substituted C3 to C6 cycloalkyl, C4 to C6 heterocycloalkyl, alkyl, alkene, 6-membered aryl or 6-membered heteroaryl;
wherein C3 to C6 cycloalkyl, aryl and heteroaryl are each optionally substituted with one, two or three substituents each selected from halogen, alkyl or amino;
provided that if A is C(R11), X is C and Y is N(R1), then R11 and R1 can join to form a 6-membered heterocyclic ring substituted with R17;
R17 is selected from hydrogen or alkyl;
or an optical isomer, diastereomer or enantiomer thereof;
a pharmaceutically acceptable salt, hydrate, or prodrug thereof.

28 more elements

A compound selected from the group consisting of:

7-[4-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-(2,4-difluoro-phenyl)-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
9-[4-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
9-[4-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
7-[4-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[4-(2-Amino-1-fluoro-ethylidene)-3-methyl-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[4-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-7-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-chloro-ethylidene)-pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-propylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(2-Amino-ethylidene)-3-hydroxy-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(2-Amino-ethylidene)-3-methoxyimino-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(2-Amino-1-methyl-ethylidene)-3-hydroxy-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
9-[4-(2-Amino-1-methyl-ethylidene)-3-hydroxy-piperidin-1-yl]-1-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
7-[4-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-8-difluoromethoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Aminomethyl-propylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Aminomethyl-propylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Chloro-2-methylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-8-difluoromethoxy-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-Cyclopropyl-8-difluoromethoxy-6-fluoro-7-[4-(1-methyl-2-methylamino-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Chloro-2-ethylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-ethylidene)-azetidin-1-yl}-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
9-[3-(2-Amino-1-chloro-ethylidene)-azetidin-1-yl}-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
7-[4-(2-Amino-1-fluoro-ethylidene)-3,3-dimethyl-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-7-[4-(1-methyl-2-methylamino-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[3-(2-Amino-1-fluoro-ethylidene)-azetidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[3-(2-Amino-1-chloro-ethylidene)-azetidin-1-yl}-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[3-(2-Amino-1-fluoro-ethylidene)-azetidin-1-yl]-1-cyclopropyl-8-difluoromethoxy-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-{4-[2-(Benzyl-methyl-amino)-1-chloro-ethylidene]-piperidin-1-yl}-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-7-[4-(2-hydroxy-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-7-[4-(2-hydroxy-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Chloro-2-isopropylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-7-[4-(1-fluoro-2-hydroxy-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(1-Aminomethyl-but-3-enylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(2-Amino-1-fluoro-ethylidene)-3,3-dimethyl-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(2-Amino-1-bromo-ethylidene)-3,3-dimethyl-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-{4-[1-Chloro-2-(2-dimethylamino-ethylamino)-ethylidene]-piperidin-1-yl}-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(1-Chloro-allylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
1-Cyclopropyl-7-[4-(2-ethoxycarbonyloxy-1-fluoro-ethylidene)-piperidin-1-yl]-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(1-Chloro-2-dimethylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(1-Chloro-2-piperidin-1-yl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
1-Cyclopropyl-7-[4-(2-dimethylamino-1-fluoro-ethylidene)-piperidin-1-yl]-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(1-Aminomethyl-but-3-enylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
1-(2,4-Difluoro-phenyl)-6-fluoro-7-[4-(2-hydroxy-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[3-(2-Amino-1-chloro-ethylidene)-azetidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Chloro-2-dimethylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Chloro-2-pyrrolidin-1-yl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Chloro-2-piperidin-1-yl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Chloro-2-morpholin-4-yl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Chloro-2-isopropylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-Cyclopropyl-7-[4-(2-dimethylamino-1-fluoro-ethylidene)-piperidin-1-yl]-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Aminomethyl-3-hydroxy-propylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Aminomethyl-3-methyl-but-3-enylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Aminomethyl-but-3-enylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-bromo-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[3-(2-Amino-1-chloro-ethylidene)-azetidin-1-yl]-1-cyclopropyl-8-difluoromethoxy-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-{4-[2-(Benzyl-methyl-amino)-1-chloro-ethylidene]-piperidin-1-yl}-1-cyclopropyl-8-difluoromethoxy-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
7-{4-[2-(Benzyl-methyl-amino)-1-fluoro-ethylidene]-piperidin-1-yl}-1-cyclopropyl-8-difluoromethoxy-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[3-(2-Amino-1-chloro-ethylidene)-azetidin-1-yl]-1-cyclopropyl-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
9-[4-(2-Amino-ethylidene)-3-hydroxy-piperidin-1-yl]-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
8-Fluoro-9-[4-(2-hydroxy-1-methyl-ethylidene)-piperidin-1-yl]-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
7-[4-(2-Amino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-7-[4-(1-fluoro-2-methylamino-ethylidene)-piperidin-1-yl]-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-Cyclopropyl-7-[4-(2-ethylamino-1-fluoro-ethylidene)-piperidin-1-yl]-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Chloro-2-methylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(1-Chloro-2-methylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-7-[4-(1-methyl-2-methylamino-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-7-[4-(1-methyl-2-methylamino-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-7-[4-(1-methyl-2-methylamino-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-Cyclopropyl-8-difluoromethoxy-6-fluoro-7-[4-(1-methyl-2-methylamino-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-8-methoxy-7-[4-(2-methylamino-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Acetylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-7-[4-(1-fluoro-2-isopropylamino-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(1-Chloro-2-isopropylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-7-[4-(1-fluoro-2-isopropylamino-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Chloro-2-isopropylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-8-difluoromethoxy-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-Cyclopropyl-8-difluoromethoxy-6-fluoro-7-[4-(1-fluoro-2-isopropylamino-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-7-[4-(1-fluoro-2-isopropylamino-ethylidene)-piperidin-1-yl]-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-8-difluoromethoxy-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-8-difluoromethoxy-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-6-fluoro-(1R,2S)-1-(2-fluoro-cyclopropyl)-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-5-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Chloro-2-methylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-hydroxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[3-(2-Amino-1-chloro-ethylidene)-azetidin-1-yl]-1-(6-amino-3,5-difluoro-pyridin-2-yl)-8-chloro-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-(6-Amino-3,5-difluoro-pyridin-2-yl)-7-[3-(2-amino-1-fluoro-ethylidene)-azetidin-1-yl]-8-chloro-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-(6-amino-3,5-difluoro-pyridin-2-yl)-8-chloro-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-(2,4-difluoro-phenyl)-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[3-(2-amino-1-fluoro-ethylidene)-azetidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[3-(2-amino-1-fluoro-ethylidene)-azetidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[3-(2-amino-1-fluoro-ethylidene)-azetidin-1-yl]-1-cyclopropyl-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
9-[3-(2-Amino-1-fluoro-ethylidene)-azetidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
9-[4-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
7-[4-(2-Amino-1-cyano-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(2-Amino-1-cyano-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-carboxy-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-{4-[2-(2-Amino-ethylamino)-1-chloro-ethylidene]-piperidin-1-yl}-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-{4-[1-Chloro-2-(4-formyl-piperazin-1-yl)-ethylidene]-piperidin-1-yl}-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(1-chloro-2-piperazin-1-yl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-7-[4-(1-fluoro-2-piperazin-1-yl-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
9-[4-(2-Dimethylamino-1-fluoro-ethylidene)-piperidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
(Z)-7-[3-(1-Amino-2-propylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-[4-(1-Chloro-2-dimethylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-Cyclopropyl-7-[4-(2-dimethylamino-1-fluoro-ethylidene)-piperidin-1-yl]-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(1-Chloro-2-piperidin-1-yl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[3-(1-Chloro-2-hydroxy-ethylidene)-azetidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[3-(1-Chloro-2-hydroxy-ethylidene)-azetidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(E)-1-(6-Amino-3,5-difluoro-pyridin-2-yl)-7-[3-(2-amino-1-fluoro-ethylidene)-piperidin-1-yl]-8-chloro-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid trifluoroacetate,
(Z)-1-(6-Amino-3,5-difluoro-pyridin-2-yl)-8-chloro-6-fluoro-7-[3-(1-fluoro-2-hydroxy-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid trifluoroacetate,
1-(6-Amino-3,5-difluoro-pyridin-2-yl)-8-chloro-7-[3-(1-chloro-2-methylamino-ethylidene)-azetidin-1-yl]-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-(6-Amino-3,5-difluoro-pyridin-2-yl)-8-chloro-7-[3-(1-chloro-2-hydroxy-ethylidene)-azetidin-1-yl]-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(S)-9-[3-(1-Chloro-2-hydroxy-ethylidene)-azetidin-1-yl]-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
7-[3-(1-Chloro-2-hydroxy-ethylidene)-azetidin-1-yl]-6-fluoro-(1R,2S)-1-(2-fluoro-cyclopropyl)-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[3-(1-Chloro-2-hydroxy-ethylidene)-azetidin-1-yl]-1-cyclopropyl-6-fluoro-5-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
9-[3-(2-Amino-ethylidene)-azetidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
9-[3-(2-Amino-1-methyl-ethylidene)-azetidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
7-[3-(2-Amino-1-methyl-ethylidene)-azetidin-1-yl]-1-cyclopropyl-6-fluoro-5-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[3-(2-Amino-1-methyl-ethylidene)-azetidin-1-yl]-6-fluoro-(1R,2S)-1-(2-fluoro-cyclopropyl)-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
5-Amino-7-[4-(2-amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-fluoromethoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-9-[4-(2-Amino-1-chloro-ethylidene)-azepan-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
9-[(E)-4-(2-Amino-1-chloro-ethylidene)-azepan-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
(Z)-7-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(Z)-7-[3-(2-Amino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(E)-7-[3-(2-Amino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(Z)-7-[4-(2-Amino-1-chloro-ethylidene)-azepan-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(E)-7-[4-(2-Amino-1-chloro-ethylidene)-azepan-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-1-(2,4-difluoro-phenyl)-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-1-(2,4-difluoro-phenyl)-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[4-(2-Amino-1-chloro-ethylidene)-azepan-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[4-(2-Amino-1-chloro-ethylidene)-azepan-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-ethylidene)-piperidin-1-yl]-1-cyclopropyl—6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[3-(2-Amino-1-methyl-ethylidene)-azetidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[4-(2-Amino-1-chloro-ethylidene)-azepan-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[4-(2-Amino-1-chloro-ethylidene)-azepan-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-8-difluoromethoxy-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-8-difluoromethoxy-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-8-difluoromethoxy-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-9-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
(Z)-9-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
(E)-9-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
(E)-9-[3-(2-Amino-ethylidene)-piperidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
(Z)-9-[3-(2-Amino-ethylidene)-piperidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
9-[3-(1-Chloro-2-hydroxy-ethylidene)-azetidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
(Z)-9-[3-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
(E)-7-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-6-fluoro-(1R,2S)-1-(2-fluoro-cyclopropyl)-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-6-fluoro-(1R,2S)-1-(2-fluoro-cyclopropyl)-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-6-fluoro-(1R,2S)-1-(2-fluoro-cyclopropyl)-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-ethylidene)-piperidin-1-yl]-6-fluoro-(1R,2S)-1-(2-fluoro-cyclopropyl)-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-ethylidene)-piperidin-1-yl]-6-fluoro-(1R,2S)-1-(2-fluoro-cyclopropyl)-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-methyl-ethylidene)-piperidin-1-yl]-6-fluoro-(1R,2S)-1-(2-fluoro-cyclopropyl)-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-1-(6-Amino-3,5-difluoro-pyridin-2-yl)-7-[3-(2-amino-1-fluoro-ethylidene)-piperidin-1-yl]-8-chloro-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-1-(6-Amino-3,5-difluoro-pyridin-2-yl)-7-[3-(2-amino-1-chloro-ethylidene)-piperidin-1-yl]8-chloro-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-1-(6-Amino-3,5-difluoro-pyridin-2-yl)-7-[3-(2-amino-ethylidene)-piperidin-1-yl]8-chloro-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-1-(6-Amino-3,5-difluoro-pyridin-2-yl)-7-[3-(2-amino-ethylidene)-piperidin-1-yl]8-chloro-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-1-(6-Amino-3,5-difluoro-pyridin-2-yl)-8-chloro-6-fluoro-7-[3-(1-fluoro-2-hydroxy-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-1-(6-Amino-3,5-difluoro-pyridin-2-yl)-8-chloro-7-[3-(1-chloro-2-hydroxy-ethylidene)-piperidin-1-yl]-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-(6-Amino-3,5-difluoro-pyridin-2-yl)-8-chloro-6-fluoro-7-[4-(1-fluoro-2-hydroxy-ethylidene)-piperidin-1-yl]-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-(6-Amino-3,5-difluoro-pyridin-2-yl)-8-chloro-6-fluoro-7-[3-(1-fluoro-2-methylamino-ethylidene)-azetidin-1-yl]-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-(6-Amino-3,5-difluoro-pyridin-2-yl)-8-chloro-6-fluoro-7-[3-(1-fluoro-2-hydroxy-ethylidene)-azetidin-1-yl]-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-(6-Amino-3,5-difluoro-pyridin-2-yl)-7-[3-(2-amino-ethylidene)-azetidin-1-yl]-8-chloro-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
1-(6-Amino-3,5-difluoro-pyridin-2-yl)-7-[3-(2-amino-1-methyl-ethylidene)-azetidin-1-yl]-8-chloro-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-1-(6-Amino-3,5-difluoro-pyridin-2-yl)-7-[3-(2-amino-1-methyl-ethylidene)-piperidin-1-yl]-8-chloro-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-1-(6-Amino-3,5-difluoro-pyridin-2-yl)-7-[3-(2-amino-1-methyl-ethylidene)-piperidin-1-yl]-8-chloro-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-5-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-5-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-5-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-5-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(1-Chloro-2-methylamino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-Cyclopropyl-6-fluoro-7-[3-(1-fluoro-2-methylamino-ethylidene)-azetidin-1-yl]-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[3-(1-Chloro-2-methylamino-ethylidene)-azetidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-cyano-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
9-[4-(2-Amino-1-cyano-ethylidene)-piperidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
7-[4-(2-Amino-1-cyano-ethylidene)-piperidin-1-yl]-1-cyclopropyl-8-difluoromethoxy-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-cyano-ethylidene)-piperidin-1-yl]-6-fluoro-(1R,2S)-1-(2-fluoro-cyclopropyl)-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-1-cyano-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-cyano-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
7-{4-[2-(2-Amino-acetylamino)-1-chloro-ethylidene]-piperidin-1-yl}-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-8-difluoromethoxy-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-9-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
(Z)-7-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-6-fluoro-(1R,2S)-1-(2-fluoro-cyclopropyl)-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-(6-amino-3,5-difluoro-pyridin-2-yl)-8-chloro-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[3-(2-Amino-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-5-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[3-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-5-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-1-Cyclopropyl-6-fluoro-7-[3-(1-fluoro-2-methylamino-ethylidene)-piperidin-1-yl]-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[4-(2-Amino-1-chloro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-5-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
5-Amino-7-[(E)-3-(2-amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[(E)-3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-fluoromethoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[(E)-3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-5-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-[(E)-3-(2-Amino-1-fluoro-ethylidene)-piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
7-{4-[3-Amino-1-fluoro-propylidene]-piperidin-1-yl}-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(3S)-9-[(Z)-4-(2-Amino-1-fluoro-ethylidene)-azepan-1-yl]-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
(3S)-9-[(E)-4-(2-Amino-1-fluoro-ethylidene)-azepan-1-yl]-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
9-[(Z)-6-(2-Amino-1-fluoro-ethylidene)-[1,4]oxazepan-4-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
9-[(E)-6-(2-Amino-1-fluoro-ethylidene)-[1,4]oxazepan-4-yl]-8-fluoro-(3S)-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid,
(Z)-7-[4-(2-Amino-1-fluoro-ethylidene)-azepan-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(E)-7-[4-(2-Amino-1-fluoro-ethylidene)-azepan-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(Z)-7-[6-(2-Amino-1-fluoro-ethylidene)-[1,4]oxazepan-4-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(E)-7-[6-(2-Amino-1-fluoro-ethylidene)-[1,4]oxazepan-4-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(Z)-7-[6-(2-Amino-1-fluoro-ethylidene)-(2S)-2-methyl-[1,4]oxazepan-4-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(Z)-7-[6-(2-Amino-1-fluoro-ethylidene)-(2R)-2-methyl-[1,4]oxazepan-4-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid,
(Z)-7-[4-(2-Amino-1-fluoro-ethylidene)-azepan-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[4-(2-Amino-1-fluoro-ethylidene)-azepan-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[6-(2-Amino-1-fluoro-ethylidene)-[1,4]oxazepan-4-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[6-(2-Amino-1-fluoro-ethylidene)-[1,4]oxazepan-4-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[4-(2-Amino-1-fluoro-ethylidene)-azepan-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(E)-7-[4-(2-Amino-1-fluoro-ethylidene)-azepan-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid,
(Z)-7-[6-(2-Amino-1-fluoro-ethylidene)-[1,4]oxazepan-4-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid, and
(E)-7-[6-(2-Amino-1-fluoro-ethylidene)-[1,4]oxazepan-4-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid.
or an optical isomer, diastereomer or enantiomer thereof or a pharmaceutically acceptable salt, hydrate, or prodrug thereof.

236 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/268,529Filed 11 Nov 2008
Priority: 9 Sep 2004
Published: 18 Jun 2009
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
C07D 401/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…

Family

Application10/937,238Continuation in part · filed 9 Sep 2004
Application11/084,987Continuation in part · filed 21 Mar 2005
Application12/268,529Continuation in part
US 2005/0101588 A1Published application
US 2006/0052359 A1Published application
US 7,179,805 B2Related patent
US 7,732,612 B2Related patent
US 2009/0156577 A1This patent

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

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Abstract

A compound having a structure according to Formula (I):

wherein:
n is an integer from 1 to 3;
m is an integer from 1 to 3;
z is an integer from 0 to 3;
R is selected from hydrogen, hydroxy, and alkoxy;
R2 is hydrogen;
R3 and R4 are independently selected from hydrogen, halogen, amino, hydroxy, alkoxy, alkylthio, alkyl, alkenyl and alkynyl;
R5 is selected from hydrogen, hydroxy, halogen, alkyl, aryl, alkoxy, cyano, CO2R13, and alkylthio;
R6 is independently selected from alkyl, hydroxy, alkoxy, alkylthio, alkenyl, alkynyl, aryl, alkoxyimino, and halogen;
or R5 and R6 join to form a 4- to 7-membered carbocyclic ring wherein each carbon atom of the ring can be optionally substituted with R12, wherein R12 is selected from the group consisting of halogen, amino, hydroxy, alkoxy, alkylthio, alkyl, alkenyl, alkynyl, oxo, alkoxyimino and hydroxyimino;
R13 is hydrogen, alkyl, aryl, or a carboxylic acid protecting group;
E is selected from the group consisting of:
wherein,
q is an integer from 1 to 3;
In the case of 1), R7 and R8 are each independently selected from hydrogen and alkyl, or R7 and R8 join to form a 3 to 6 membered carbocyclic ring, or either of R7 or R8 can be joined independently to either of R9 or R10 to form a heterocyclic ring containing the nitrogen atom to which R9 or R10 are bonded, wherein
R9 and R10 are each independently selected from hydrogen, alkyl, aryl, arylalkyl, acyl, alkoxycarbonyl, or sulfonyl, or alternatively R9 and R10 join to form a heterocyclic ring containing the nitrogen atom to which they are bonded;
In the case of 2), R7 and R8 are each independently selected from hydrogen and alkyl, or R7 and R8 join to form a 3- to 6-membered carbocyclic ring, and R9 is selected from hydrogen, alkyl, acyl, alkoxycarbonyl, or sulfonyl;
A is selected from N and C(R11), wherein R11 is selected from hydrogen, alkyl, halogen, hydroxy, alkoxy, alkylthio or cyano;
X is selected from C and N, where if X is C, then a is a double bond and b is a single bond, and if X is N, then a is a single bond and b is a double bond;
and
Y is selected from N(R1) and C(R1), with the proviso that when Y is N(R1), then X is C and when Y is C(R1), then X is N;
wherein
R1 is selected from C3 to C6 cycloalkyl, C4 to C6 heterocycloalkyl, alkyl, alkene, a 6-membered aryl and a 6-membered heteroaryl;
provided that
if A is C(R11), X is C and Y is N(R1), then R11 and R1 can join to form a 6-membered heterocyclic ring optionally substituted by one or more alkyl groups for a corresponding hydrogen atom;
or
if A is C(R11), X is C and Y is N(R1), then R2 and R1 can join to form a monocyclic or bicyclic heterocyclic ring optionally substituted by one or more alkyl groups for a corresponding hydrogen atom;
or
if A is C(R11), X is C and Y is N(R1), then R2 and R can join to form a 5-membered heterocyclic ring optionally substituted by one or more alkyl groups for a corresponding hydrogen atom;
or an optical isomer, diastereomer or enantiomer thereof or a pharmaceutically acceptable salt, hydrate, or prodrug thereof.

27 more elements

Facts

Application

12/268,529Filed 11 Nov 2008

Priority

9 Sep 2004

Published

18 Jun 2009

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
C07D 401/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…

Family

Application10/937,238Continuation in part · filed 9 Sep 2004

Application11/084,987Continuation in part · filed 21 Mar 2005

Application12/268,529Continuation in part

US 2005/0101588 A1Published application

US 2006/0052359 A1Published application

US 7,179,805 B2Related patent

US 7,732,612 B2Related patent

US 2009/0156577 A1This patent

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