IP Library › Granted Patent US 8,901,119
Granted Patent B2
US 8,901,119 · App. 14/004,105 · Granted Dec 2, 2014

Peptide deformylase inhibitors

Inventors: Kelly M. Aubart (Collegeville, PA); Andrew B. Benowitz (Collegeville, PA); Yuhong Fang (Eagleville, PA); James Hoffman (Ardmore, PA); Joseph M. Karpinski (Stowe, PA); Andrew Nicholson Knox (Philadelphia, PA); Xiangmin Liao (Collegeville, PA); Donghui Qin (Collegeville, PA); Dongchuan Shi (Collegeville, PA); Jared T. Spletstoser (Collegeville, PA)
Assignee: GlaxoSmithKline Intellectual Property (No. 2) Limited
C07K5/06139C07D401/12C12Y305/01088C07D403/12C07D231/06
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Quick Facts
Patent No.
US 8,901,119
App. No.
14/004,105
Granted
Dec 2, 2014
Kind
B2
Abstract

The present invention relates to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, corresponding pharmaceutical compositions, compound preparation and treatment methods directed to bacterial infections and inhibition of bacterial peptide deformylase (PDF) activity.

Claims (228)

1. A compound of Formula (I):

wherein:

X—Y is —C(H) 2 —N(R a )— or —C(H)═N—;

R is —C(O)N(H)OH or —N(OH)C(O)H;

R 1 is —H or —C 1 -C 6 alkyl;

R 2 is aryl, —(CH 2 ) n -aryl, heteroaryl or —(CH 2 )heteroaryl;

R 3 is —H or —C 1 -C 6 alkyl;

R 4 is —H, halo, —OH, C 1 -C 3 alkoxy, —NR 6 R 7 or C 1 -C 6 alkyl;

R 5 is —H, halo, —OH, C 1 -C 3 alkoxy, —NR 6 R 7 or C 1 -C 6 alkyl;

R 9 is —C 3 -C 6 cycloalkyl or —C 1 -C 6 alkyl;

wherein:

n is 0 or an integer from 1 to 5;

R a is —H or —C 1 -C 3 alkyl;

each aryl or heteroaryl as defined in R 2 optionally is substituted with one, two, or three R 8 groups;

R 6 is —H or —C 1 -C 6 alkyl;

R 7 is —H or —C 1 -C 6 alkyl;

R 8 each independently is selected from —C 1 -C 6 alkyl, —C 1 -C 6 haloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)OR 10 , —OR 11 , —NR 10 R 11 , —O(CH 2 ) 2 NR 10 R 11 , —(CH 2 )NR 10 R 11 or —N(H)(CH 2 ) 3 —NR 10 R 11 ;

wherein:

R 10 or R 11 each independently is —H or —C 1 -C 6 alkyl;

heterocyclyl, aryl or heteroaryl optionally is substituted with at least one R 12 group;

wherein:

R 12 is —C 1 -C 6 alkyl, —NR 13 R 14 , OR 15 or halo;

 wherein:

 R 13 , R 14 or R 15 each independently is —H or —C 1 -C 6 alkyl; or

a pharmaceutically acceptable salt thereof.

2. A compound of Formula (II):

wherein:

R a is —H or —C 1 -C 3 alkyl;

R is —C(O)N(H)OH or —N(OH)C(O)H;

R 1 is —H or —C 1 -C 6 alkyl;

R 2 is aryl, —(CH 2 ) n -aryl, heteroaryl or —(CH 2 )heteroaryl R 3 is —H or —C 1 -C 6 alkyl;

R 9 is —C 3 -C 6 cycloalkyl or —C 1 -C 6 alkyl;

wherein:

n is 0 or an integer from 1 to 5;

each aryl or heteroaryl as defined in R 2 optionally is substituted with one, two, or three R 8 groups;

R 8 each independently is selected from —C 1 -C 6 alkyl, —C 1 -C 6 haloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)OR 10 , —OR 10 , —NR 10 R 11 , —O(CH 2 ) 2 NR 10 R 11 , —(CH 2 )NR 10 R 11 or —N(H)(CH 2 ) 3 —NR 10 R 11 ;

wherein:

R 10 or R 11 each independently is —H or —C 1 -C 6 alkyl;

heterocyclyl, aryl or heteroaryl optionally is substituted with at least one R 12 group;

wherein:

R 12 is —C 1 -C 6 alkyl, —NR 13 R 14 , OR 15 or halo;

 wherein:

 R 13 , R 14 or R 15 each independently is —H or —C 1 -C 6 alkyl; or

a pharmaceutically acceptable salt thereof.

3. A compound of Formula (III):

wherein:

R is —C(O)N(H)OH or —N(OH)C(O)H R 1 is —H or —C 1 -C 6 alkyl;

R 2 is aryl, —(CH 2 ) n -aryl, heteroaryl or —(CH 2 )heteroaryl R 3 is —H or —C 1 -C 6 alkyl;

wherein:

n is 0 or an integer from 1 to 5;

each aryl or heteroaryl as defined in R 2 optionally is substituted with one, two, or three R 8 groups;

R 8 each independently is selected from —C 1 -C 6 alkyl, —C 1 -C 6 haloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)OR 10 , —OR 10 , —NR 10 R 11 , —O(CH 2 ) 2 NR 10 R 11 , —(CH 2 )NR 10 R 11 or —N(H)(CH 2 ) 3 —NR 10 R 11 ;

wherein:

R 10 or R 11 each independently is —H or —C 1 -C 6 alkyl;

heterocyclyl, aryl or heteroaryl optionally is substituted with at least one R 12 group;

wherein:

R 12 is —C 1 -C 6 alkyl, —NR 13 R 14 , OR 15 or halo;

 wherein:

 R 13 , R 14 or R 15 each independently is —H or —C 1 -C 6 alkyl; or

a pharmaceutically acceptable salt thereof.

4. A compound of Formula (IV)

wherein:

R a is —H or —C 1 -C 3 alkyl;

R 2 is aryl, —(CH 2 ) n -aryl, heteroaryl or —(CH 2 )heteroaryl;

wherein:

n is 0 or an integer from 1 to 5;

each aryl or heteroaryl as defined in R 2 optionally is substituted with one, two, or three R 8 groups;

R 8 each independently is selected from —C 1 -C 6 alkyl, —C 1 -C 6 haloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)OR 10 , —OR 10 , —NR 10 R 11 , —O(CH 2 ) 2 NR 10 R 11 , —(CH 2 )NR 10 R 11 or —N(H)(CH 2 ) 3 —NR 10 R 11 ;

wherein:

R 10 or R 11 each independently is —H or —C 1 -C 6 alkyl;

heterocyclyl, aryl or heteroaryl optionally is substituted with at least one R 12 group;

wherein:

R 12 is —C 1 -C 6 alkyl, —NR 13 R 14 , —OR 15 or halo;

 wherein:

 R 13 , R 14 or R 15 each independently is —H or —C 1 -C 6 alkyl; or

a pharmaceutically acceptable salt thereof.

5. A compound which is

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(3-methyl-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(3,4-dimethyl-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(6-ethyl-3-methyl-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-4-isoquinolinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(6-ethyl-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(4-ethyl-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-1,3-thiazol-2-yl-3-pyrazolidinecarboxamide;

(3S)—N-(5-Chloro-2-pyridinyl)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-3-isoxazolyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-phenyl-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[3-(methyloxy)phenyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(4-fluorophenyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(3-fluorophenyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(4,5-dimethyl-1,3-thiazol-2-yl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-phenyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-fluoro-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-2-pyridinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-3-pyridinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-3-pyridazinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[4-(trifluoromethyl)phenyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(2-fluorophenyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(6-fluoro-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[4-(trifluoromethyl)-2-pyridinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(2-pyridinylmethyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(6-methyl-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[6-(trifluoromethyl)-2-pyridinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(4,6-dimethyl-2-pyridinyl)-3-pyrazolidinecarboxamide;

Ethyl 5-({[(3S)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-3-pyrazolidinyl]carbonyl}amino)-1,3,4-oxadiazole-2-carboxylate;

(3S)—N-(6-Chloro-2-pyridinyl)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[6-(4-morpholinyl)-3-pyridinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-5-isoquinolinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-1-isoquinolinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-2-quinolinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-3-quinolinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-{5-[4-(methyloxy)phenyl]-2-pyridinyl}-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-{5-[3-(methyloxy)phenyl]-2-pyridinyl}-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-5-quinolinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[6-(4-morpholinyl)-2-pyridinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(1,2,3,4-tetrahydro-5-quinolinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-8-quinolinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[5-(4-fluorophenyl)-2-pyridinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[6-(methyloxy)-1,5-naphthyridin-3-yl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-fluoro-1-oxido-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-methyl-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(1-oxido-2-pyridinyl)-3-pyrazolidinecarboxamide;

Methyl 6-({[(3S)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-3-pyrazolidinyl]carbonyl}amino)-2-pyridinecarboxylate;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-methyl-3-isoxazolyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(2-fluoro-3-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(1-oxido-4-pyrimidinyl)-3-pyrazolidinecarboxamide;

(3S)—N-1H-1,2,3-Benzotriazol-5-yl-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-1-methyl-N-4-pyrimidinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-fluoro-2-pyridinyl)-1-methyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-1-methyl-N-2-pyrazinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-1-methyl-N-[2-(methyloxy)-4-pyrimidinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-1-methyl-N-[6-(methyloxy)-2-pyrazinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(6-fluoro-2-pyridinyl)-1-methyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(3-fluoro-4-pyridinyl)-1-methyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-1-methyl-N-[3-(methyloxy)-2-pyrazinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-4-pyrimidinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-2-pyrazinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-4-pyridinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[6-(1H-imidazol-1-yl)-2-pyridinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[5-(1H-imidazol-1-yl)-2-pyridinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(3-fluoro-4-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(2-quinolinylmethyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-5-pyrimidinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[6-(methyloxy)-4-pyrimidinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(4-methyl-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(7-methyl-7H-purin-6-yl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[2-(methyloxy)-4-pyrimidinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-fluoro-4-pyrimidinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(3-quinolinylmethyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-methyl-2-pyrazinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[6-(methyloxy)-2-pyrazinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[3-(methyloxy)-2-pyrazinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(2-fluoro-4-pyrimidinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[2-(4-methyl-1-piperazinyl)-4-pyrimidinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[2-(dimethylamino)-4-pyrimidinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(4-pyrimidinylmethyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-{2-[(2R)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(2-{[2-(dimethylamino)ethyl]oxy}-4-pyrimidinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(2-{[3-(dimethylamino)propyl]amino}-4-pyrimidinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-{2-[(3S)-3-(dimethylamino)-1-pyrrolidinyl]-4-pyrimidinyl}-3-pyrazolidine carboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-2-pyrimidinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-{6-[(2R)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[2-(4-methyl-4,7-diazaspiro[2.5]oct-7-yl)-4-pyrimidinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-{2-[(2S)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[5-(methyloxy)-2-pyrimidinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[4-(methyloxy)-2-pyrimidinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-fluoro-2-pyrimidinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-{2-[(dimethylamino)methyl]-4-pyrimidinyl}-3-pyrazolidinecarboxamide;

(5S)-1-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-4-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamide;

(5S)-1-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-fluoro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide;

(5S)-1-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-fluoro-4-pyrimidinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide;

(5S)-1-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-2-pyrazinyl-4,5-dihydro-1H-pyrazole-5-carboxamide;

(5S)-1-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(2-fluoro-4-pyrimidinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide;

(5S)-1-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-methyl-2-pyrazinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide;

(5S)-1-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(6-fluoro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide;

(5S)-1-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[2-(methyloxy)-4-pyrimidinyl]-4,5-dihydro-1H-pyrazole-5-carboxamide;

(3S)—N-(5-Fluoro-2-pyridinyl)-2-((2R)-2-{[formyl(hydroxy)amino]methyl}heptanoyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-2-{[Formyl(hydroxy)amino]methyl}heptanoyl)-N-4-pyrimidinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-2-{[Formyl(hydroxy)amino]methyl}heptanoyl)-N-2-pyridinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-2-{[Formyl(hydroxy)amino]methyl}heptanoyl)-N-(1-oxido-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)—N-(5-Fluoro-1-oxido-2-pyridinyl)-2-((2R)-2-{[formyl(hydroxy)amino]methyl}heptanoyl)-3-pyrazolidinecarboxamide;

(5S)-1-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(1-oxido-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-1H-imidazol-2-yl-3-pyrazolidinecarboxamide;

(3S)—N-1H-Benzimidazol-2-yl-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-3-pyrazolidinecarboxamide;

(5S)—N-(5-Fluoro-2-pyridinyl)-1-((2R)-2-{[formyl(hydroxy)amino]methyl}heptanoyl)-4,5-dihydro-1H-pyrazole-5-carboxamide;

(5S)-1-((2R)-2-{[Formyl(hydroxy)amino]methyl}heptanoyl)-N-2-pyridinyl-4,5-dihydro-1H-pyrazole-5-carboxamide;

(5S)-1-((2R)-2-{[Formyl(hydroxy)amino]methyl}heptanoyl)-N-4-pyrimidinyl-4,5-dihydro-1H-pyrazole-5-carboxamide;

(3S)-2-((2R)-2-{[Formyl(hydroxy)amino]methyl}heptanoyl)-N-3-pyridazinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[2-(4-morpholinyl)-5-pyrimidinyl]-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-2-{[Formyl(hydroxy)amino]methyl}hexanoyl)-N-(1-oxido-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)—N-(5-Fluoro-1-oxido-2-pyridinyl)-2-((2R)-2-{[formyl(hydroxy)amino]methyl}hexanoyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-2-{[Formyl(hydroxy)amino]methyl}hexanoyl)-N-4-pyrimidinyl-3-pyrazolidinecarboxamide;

4-({[(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-3-pyrazolidinyl]carbonyl}amino)benzoic acid;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-hydroxy-2-pyridinyl)-3-pyrazolidinecarboxamide;

6-({[(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-3-pyrazolidinyl]carbonyl}amino)-3-pyridinecarboxylic acid;

2-({[(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-3-pyrazolidinyl]carbonyl}amino)-4-pyridinecarboxylic acid;

3-({[(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-3-pyrazolidinyl]carbonyl}amino)benzoic acid;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(4-hydroxy-2-pyridinyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(3-hydroxyphenyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(4-hydroxyphenyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[2-(2-pyridinyl)-5-pyrimidinyl]-3-pyrazolidinecarboxamide;

(3S)—N-(5-Fluoro-2-pyridinyl)-2-((2R)-2-{[formyl(hydroxy)amino]methyl}hexanoyl)-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-2-{[Formyl(hydroxy)amino]methyl}hexanoyl)-N-3-pyridazinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-2-{[Formyl(hydroxy)amino]methyl}hexanoyl)-N-2-pyridinyl-3-pyrazolidinecarboxamide;

(3S)-2-((2R)-3-Cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-[4-(2-pyridinyl)-2-pyrimidinyl]-3-pyrazolidinecarboxamide; or

a pharmaceutically acceptable salt thereof.

6. A compound which is (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-4-pyrimidinyl-3-pyrazolidinecarboxamide:

or a pharmaceutically acceptable salt thereof.

7. A compound which is (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-4-pyrimidinyl-3-pyrazolidinecarboxamide:

8. A pharmaceutical composition comprising a compound of Formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient.

9. A pharmaceutical composition comprising a compound according to claim 6 and a pharmaceutically acceptable excipient.

10. A pharmaceutical composition comprising a compound according to claim 7 and a pharmaceutically acceptable excipient.

11. A method for treatment of a bacterial infection comprising administering an effective amount of a compound of Formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof to a human suffering from said bacterial infection.

12. The method according to claim 11 , wherein the bacterial infection is caused by Streptococcus, Staphylococcus, Moraxella, Haemophilus, Neisseria, Mycoplasma, Legionella, Chlamydia, Bacteroides, Clostridium, Fusobacterium, Propionibacterium , or Peptostreptococcus.

13. The method according to claim 12 , wherein the bacterial infection is caused by:

Streptococcus selected from S. pneumoniae or S. pyogenes;

Staphylococcus selected from S. aureus, S. epidermidis , or S. saprophyticus;

Moraxella selected from M. catarrhalis;

Haemophilus selected from H. influenza or Neisseria;

Mycoplasma selected from M pneumonia;

Legionella selected from L. pneumophila ; or

Chlamydia selected from C. pneumoniae, Bacteroides, Clostridium, Fusobacterium, Propionibacterium or Peptostreptococcus.

14. A method for treatment of a bacterial infection comprising administering an effective amount of a compound according to claim 5 or a pharmaceutically acceptable salt thereof to a human suffering from said bacterial infection.

15. A method for treatment of a bacterial infection comprising administering an effective amount of a compound according to claim 6 or a pharmaceutically acceptable salt thereof to a human suffering from said bacterial infection.

16. A method for treatment of a bacterial infection comprising administering an effective amount of a compound according to claim 7 or a pharmaceutically acceptable salt thereof to a human suffering from said bacterial infection.

17. A method for treatment of a bacterial infection comprising administering an effective amount of a pharmaceutical composition according to claim 8 to a human suffering from said bacterial infection.

18. A method for treatment of a bacterial infection comprising administering an effective amount of a pharmaceutical composition according to claim 9 to a human suffering from said bacterial infection.

19. A method for treatment of a bacterial infection comprising administering an effective amount of a pharmaceutical composition according to claim 10 to a human suffering from said bacterial infection.

Assignments (2)
CHANGE OF NAME Recorded Aug 13, 2014
From: GLAXOSMITHKLINE LLC
To: GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED
Reel/Frame 033526/0804 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 5, 2014
From: AUBART, KELLY M.; BENOWITZ, ANDREW B.; FANG, YUHONG; HOFFMAN, JAMES; KARPINSKI, JOSEPH M.; KNOX, ANDREW NICHOLSON; LIAO, XIANGMIN; QIN, DONGHUI; SHI, DONGCHUAN; SPLETSTOSER, JARED T.
To: GLAXOSMITHKLINE LLC
Reel/Frame 033466/0077 →
Continuity (2)
Provisional Application 61450784 · Mar 9, 2011
Related Publication 20130345120A1 · Dec 26, 2013