US 9,169,209 B2Granted

Compounds and compositions for the inhibition of NAMPT

AssigneeForma Tm, LLC

InventorsKenneth W. Bair, Timm Baumeister, Alexandre J. Buckmelter, Karl H. Clodfelter, Bingsong Han, Jian Lin, Dominic J. Reynolds, Chase C. Smith, Zhongguo Wang, Xiaozhang Zheng

Life of this patent

Estimating the term…

Abstract

The present invention relates to compounds and composition for inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below.

Claims22

Dependent claims

A compound of Formula IB:

wherein:
Ar is aryl or heteroaryl, each of said aryl and heteroaryl being either unsubstituted or optionally independently substituted with 1, 2, 3, or 4 substituents which can be the same or different and are independently selected from the group consisting of:
deuterium, halo, cyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH2, —C(O)NH(alkyl), —C(O)N(alkyl)2, —C(O)NH(aryl), —C(O)N(aryl)2, —CHzF3-z, —OCHzF3-z, -alkyl, -alkenyl, -alkynyl, -alkoxy, (alkoxyalkyl)amino-, —N(R3)—C(O)-alkyl, —N(R3)—C(O)-aryl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;
R1 is —NRaRb, wherein Ra is H, alkyl, or —S(O)2alkyl and Rb is alkyl, hydroxyalkyl, —S(O)2alkyl, —(CH2)qcycloalkyl, —(CH2)qheterocycloalkyl, aryl, arylalkyl-, —(CH2)qheteroaryl;
cycloalkyl;
heterocycloalkyl;
aryl;
heteroaryl;
each of said cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents which can be the same or different and are independently selected from the group consisting of:
deuterium, halo, cyano, alkyl, hydroxyl, hydroxyalkyl, hydroxyalkoxy, cyanoalkyl, haloalkyl, alkenyl, alkynyl, alkoxy, alkylalkoxy, haloalkoxy, arylalkenyl-, aryloxy, benzyloxy, oxo, —(CH2)q—NRcRd, —(CH2)q—CONRcRd, —S(O)2-alkyl, —S(O)2-aryl, S(O)2NH2, —S(O)2NH-alkyl, —S(O)2N(alkyl)2, —S(O)2-heterocycloalkyl, —S(O)2—CF3, —C(O)alkyl, —C(O)aryl, —C(O)alkylenylaryl, —C(O)O-alkyl, —NH—C(O)alkyl, —NH—C(O)aryl, methylenedioxy, —(CH2)qcycloalkyl, cycloalkylalkoxy-, aryl, arylalkyl-, —(CH2)qheteroaryl, and —(CH2)qheterocycloalkyl,
wherein each of said cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted by one or more halo, nitro, haloalkyl, haloalkoxy, oxo, cyano, alkyl, haloalkyl, or alkoxy and;
Rc and Rd are independently selected from the group consisting of H, alkyl, hydroxyalkyl, alkoxy, aryl, alkoxyalkyl, —S(O)2alkyl and cycloalkyl or RC and Rd can form a 5 or 6 membered heterocycloalkyl group together with the nitrogen atom to which they are attached, wherein said heterocycloalkyl group may contain one or more addional heteroatom(s) selected from N, S or O;
z is 0, 1 or 2;
q is 0, 1, 2, 3 or 4;
or a pharmaceutically acceptable salt thereof, with the proviso that the compound of formula IB is not:
N-[3-(cyclopentylsulfonyl)phenyl]-3-(3-pyridinyl)-2-propenamide;
N-[4-ethoxy-3-(4-morpholinylsulfonyl)phenyl]-3-(3-pyridinyl)-2-propenamide;
N-[2-(1-methylethoxy)-5-(4-morpholinylsulfonyl)phenyl]-3-(3-pyridinyl)-2-propenamide;
N-[2-ethoxy-5-(4-morpholinylsulfonyl)phenyl]-3-(3-pyridinyl)-2-propenamide;
N-[5-[(hexahydro-1Hazepin-1-yl)sulfonyl]-2-(2,2,2-trifluoroethoxy)phenyl]-3-(3-pyridinyl)-2-propenamide;
N-[5-[(diethylamino)sulfonyl]-2-(4-morpholinyl)phenyl]-3-(3-pyridinyl)-2-propenamide;
N-[3-[[(3-chlorophenyl)amino]sulfonyl]-4-methylphenyl]-3-(3-pyridinyl)-2-propenamide;
N-[3-[[(4-chlorophenyl)amino]sulfonyl]-4-methylphenyl]-3-(3-pyridinyl)-2-propenamide;
3-(3-pyridinyl)-N-[4-[[(tetrahydro-1,1-dioxido-3-thienyl)amino]sulfonyl]phenyl]-2-propenamide;
3-(3-pyridinyl)-N-[3-[[[3-(trifluoromethyl)phenyl]amino]sulfonyl]phenyl]-2-propenamide;
or 3-(3-pyridinyl)-N-[1,4,5,6-tetrahydro-5-[(4-methylphenyl)sulfonyl]pyrrolo[3,4-c]pyrazol-3-yl]-2-propenamide.

23 more elements

A compound selected from the group consisting of:

(2E)-N-(4-{[3-fluoro-5-(2-methylpropoxy)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-fluoro-4-propoxybenzene)sulfonyl]phenyl}-3- (pyridin-3-yl)prop-2-enamide;
4-(phenoxathiine-4-sulfonyl)phenyl]-3- (pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(2,5-dichlorobenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
N-ethyl-3-({4-[(2E)-3-(pyridin-3-yl)prop-2-enamido]benzene}sulfonyl)benzamide;
4-(2H-1,3-benzodioxole-5- sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
4-(2,3-dihydro-1-benzofuran-7- sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(4-fluoro-3-methylbenzene)sulfonyl]phenyl}-3 -(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(2-methoxybenzene)sulfonyl]phenyl}-3- (pyridin-3-yl)prop-2-enamide 4-(2-methylpyridine-3-sulfonyl)phenyl]-3- (pyridin-3-yl)prop-2-enamide;
(2E)-N-(4-{[4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
4-(naphthalene-1-sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-fluoro-4-methoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(4-chlorobenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
N-ethyl-4-({4-[(2E)-3- (pyridin-3-yl)prop-2-enamido]benzene}sulfonyl)benzamide;
(2E)-N-{4-[(3-chloro-4-propoxybenzene)sulfonyl]phenyl}-3 -(pyridin-3-yl)prop-2-enamide;
(2E)-N- (4-{[3-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(5-chloro-2-ethoxybenzene)sulfonyl]phenyl}-3- (pyridin-3-yl)prop-2-enamide;
4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]-3- (pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-chloro-4-methoxybenzene)sulfonyl]phenyl}-3- (pyridin-3-yl)prop-2-enamide;
(2E)-3- (pyridin-3-yl)-N-(4-{[4-(trifluoromethyl)benzene]sulfonyl}phenyl)prop-2-enamide;
(2E)-3- (pyridin-3-yl)-N-(4-{[3-(trifluoromethoxy)benzene]sulfonyl}phenyl)prop-2-enamide;
(2E)-N-(4-{[2-methoxy-5-(propan-2-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
4-(1H-indole-7- sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-3-(pyridin-3-yl)-N-{4-[5-(pyrrolidin-1-yl)pyridine-3-sulfonyl]phenyl}prop-2-enamide;
(2E)-N- (4-{[3-chloro-5-(trifluoromethyl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
4-(1-methyl-1H-indole-2-sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-3-(pyridin-3-yl)-N-(4-{[4-(trifluoromethoxy)benzene]sulfonyl}phenyl)prop-2-enamide;
(2E)-N-{4-[(3-chloro-4-methylbenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
4-(6-methoxynaphthalene-2-sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(4-ethoxy-3-fluorobenzene)sulfonyl]phenyl}-3 -(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-fluoro-5-methylbenzene)sulfonyl]phenyl}-3 -(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3,4-dimethoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[4-(morpholin-4-yl)piperidine-1 -sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-3-(pyridin-3-yl)-N-[4-(quinoline-3-sulfonyl)phenyl]prop-2-enamide;
(2E)-N-(4-{[2-chloro-5-(trifluoromethoxy)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(4-phenylbenzene)sulfonyl]phenyl }-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-fluorobenzene)sulfonyl]phenyl }-3- (pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-methylbenzene)sulfonyl]phenyl }-3- (pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3,5-dimethoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
4-(5-methoxypyridine-3- sulfonyl)phenyl]-3- (pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-chlorobenzene)sulfonyl]phenyl}-3- (pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-chloro-5-methoxybenzene)sulfonyl]phenyl}-3- (pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-methanesulfonamidobenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
4-(5-methylpyridine-3-sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-(4-{[3-(methoxymethyl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(4-{8-oxa-3-azabicyclo [3.2.1]octane-3-sulfonyl}phenyl)methyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3,5-dimethylbenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(5-fluoro-2-methylbenzene)sulfonyl]phenyl}-3 -(pyridin-3-yl)prop-2-enamide;
(2E)-3-(pyridin-3-yl)-N-(4-{[2-(trifluoromethoxy)phenyl]sulfamoyl}phenyl)prop-2-enamide;
4-(6-methylpyridine-3-sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
4-(isoquinoline-4-sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
3-chloro-N,N-diethyl-5-({4-[(2E)-3-(pyridin-3-yl)prop-2-enamido]benzene}sulfonyl)benzamide;
(2E)-N-{4-[(4-methoxy-3-methylbenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
4-(benzenesulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
N-cyclopentyl-3-({4-[(2E)-3-(pyridin-3-yl)prop-2-enamido]benzene}sulfonyl)benzamide;
(2E)-N-{4-[(3-methanesulfonylbenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[2-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl }-3-(pyridin-3-yl)prop-2-enamide;
(2E)-3-(pyridin-3-yl)-N-(4-{[2-(trifluoromethoxy)benzene]sulfonyl}phenyl)prop-2-enamide;
N-(propan-2-yl)-3-({4-[(2E)-3- (pyridin-3-yl)prop-2-enamido]benzene}sulfonyl)benzamide;
(2E)-3- (pyridin-3-yl)-N-(4-{[3-(trifluoromethyl)benzene]sulfonyl}phenyl)prop-2-enamide;
4-(1-benzothiophene-7-sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[2-(dimethylamino)pyrimidine-5-sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(4-ethoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-fluoro-4-methylbenzene)sulfonyl]phenyl }-3 -(pyridin-3-yl)prop-2-enamide;
4-(1H-indole-4-sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{[4-(benzenesulfonyl)phenyl]methyl }-3-(pyridin-3-yl)prop-2-enamide;
(2E)-3-(pyridin-3-yl)-N-[4-(quinoline-8-sulfonyl)phenyl]prop-2-enamide;
(2E)-N-(4-{[2-methoxy-5-(trifluoromethoxy)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-ethoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
4-(5-methylthiophene-2-sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(4-chloro-3-methoxybenzene)sulfonyl]phenyl}-3- (pyridin-3-yl)prop-2-enamide;
(2E)-N-(4-{[2-methoxy-4-(trifluoromethyl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
N-(2-methylpropyl)-3-({4-[(2E)-3-(pyridin-3 -yl)prop-2-enamido]benzene}sulfonyl)benzamide;
N-cyclopropyl-3-({4-[(2E)-3-(pyridin-3-yl)prop-2-enamido]benzene}sulfonyl)benzamide;
(2Z)-N-[4-(benzenesulfonyl)phenyl]-2-fluoro-3- (pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-fluoro-5-methoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N- (4-{[2-methyl-4-(trifluoromethyl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl1-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-(4-{[4-(ethoxymethyl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(4-methanesulfonylbenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(4-methoxy-3,5-dimethylbenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(5-chloro-2-methoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-(4-{[4-(morpholin-4-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-3-(pyridin-3-yl)-N-[4-(pyridine-3-sulfonyl)phenyl]prop-2-enamide;
(2E)-N-(4-{[3-(propan-2-yloxy)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(4-chloro-2-methoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N- (4-{[3-(2-methylpropoxy)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-ethylbenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-3-(pyridin-3-yl)-N-[4-(quinoline-6-sulfonyl)phenyl]prop-2-enamide;
(2E)-N-{4-[(3-chloro-5-methylbenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(2-methoxy-5-methylbenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide
(2E)-N-{4-[(3,5-dichlorobenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-(4-{[3-(morpholin-4-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-(4-{[3-(3,5-dimethyl-1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-propoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-(4-{8-oxatricyclo[7.4.0.02,7]trideca-1(13),2,4,6,9, 11-hexaene-6-sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(5-fluoro-2-methoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-(4-{[4-(propan-2-yloxy)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-(4-{[3-chloro-4-(trifluoromethyl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-3-(pyridin-3-yl)-N-{4-[(3-sulfamoylbenzene)sulfonyl]phenyl }prop-2-enamide;
(2E)-N-{4-[(3-methoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(2-methylbenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
4-(2H-1,3-benzodioxole-4- sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-ethanesulfonamidobenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(4-fluorobenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
4-(4-methylpyridine-3-sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3,4-dichlorobenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
4-(1-methyl-1H-pyrazole-4-sulfonyl)phenyl]-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-(4-{[4-chloro-3-(trifluoromethyl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-(4-{[2-methoxy-5-(trifluoromethyl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N- (4-{[3-(ethanesulfonyl)benzene]sulfonyl}phenyl)-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-chloro-5-fluorobenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(4-chloro-2-ethoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
(2E)-N-{4-[(3-phenylbenzene)sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
and
(2E)-N-{4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}-3-(pyridin-3-yl)prop-2-enamide;
and pharmaceutically acceptable salts thereof.

116 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/115,623Filed 2 Sep 2011 · us provisional application
Priority: 4 May 2011
Published: US 2014/0275057 A118 Sep 2014
Granted: 27 Oct 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification43 codes

C07D 213/56
Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals: amides
A61K 31/4406
Non condensed pyridines; Hydrogenated derivatives thereof: only substituted in position 3, e.g. zimeldine
A61K 31/4439
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone

Family

Application61/482,537Us provisional application · filed 4 May 2011
US 2014/0275057 A1Pre-grant publication · published 18 Sep 2014
US 9,169,209 B2This patent

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

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Abstract

The present invention relates to compounds and composition for inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below.

A compound of Formula IB:

wherein:
Ar is aryl or heteroaryl, each of said aryl and heteroaryl being either unsubstituted or optionally independently substituted with 1, 2, 3, or 4 substituents which can be the same or different and are independently selected from the group consisting of:
deuterium, halo, cyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH2, —C(O)NH(alkyl), —C(O)N(alkyl)2, —C(O)NH(aryl), —C(O)N(aryl)2, —CHzF3-z, —OCHzF3-z, -alkyl, -alkenyl, -alkynyl, -alkoxy, (alkoxyalkyl)amino-, —N(R3)—C(O)-alkyl, —N(R3)—C(O)-aryl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;
R1 is —NRaRb, wherein Ra is H, alkyl, or —S(O)2alkyl and Rb is alkyl, hydroxyalkyl, —S(O)2alkyl, —(CH2)qcycloalkyl, —(CH2)qheterocycloalkyl, aryl, arylalkyl-, —(CH2)qheteroaryl;
cycloalkyl;
heterocycloalkyl;
aryl;
heteroaryl;
each of said cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents which can be the same or different and are independently selected from the group consisting of:
deuterium, halo, cyano, alkyl, hydroxyl, hydroxyalkyl, hydroxyalkoxy, cyanoalkyl, haloalkyl, alkenyl, alkynyl, alkoxy, alkylalkoxy, haloalkoxy, arylalkenyl-, aryloxy, benzyloxy, oxo, —(CH2)q—NRcRd, —(CH2)q—CONRcRd, —S(O)2-alkyl, —S(O)2-aryl, S(O)2NH2, —S(O)2NH-alkyl, —S(O)2N(alkyl)2, —S(O)2-heterocycloalkyl, —S(O)2—CF3, —C(O)alkyl, —C(O)aryl, —C(O)alkylenylaryl, —C(O)O-alkyl, —NH—C(O)alkyl, —NH—C(O)aryl, methylenedioxy, —(CH2)qcycloalkyl, cycloalkylalkoxy-, aryl, arylalkyl-, —(CH2)qheteroaryl, and —(CH2)qheterocycloalkyl,
wherein each of said cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted by one or more halo, nitro, haloalkyl, haloalkoxy, oxo, cyano, alkyl, haloalkyl, or alkoxy and;
Rc and Rd are independently selected from the group consisting of H, alkyl, hydroxyalkyl, alkoxy, aryl, alkoxyalkyl, —S(O)2alkyl and cycloalkyl or RC and Rd can form a 5 or 6 membered heterocycloalkyl group together with the nitrogen atom to which they are attached, wherein said heterocycloalkyl group may contain one or more addional heteroatom(s) selected from N, S or O;
z is 0, 1 or 2;
q is 0, 1, 2, 3 or 4;
or a pharmaceutically acceptable salt thereof, with the proviso that the compound of formula IB is not:
N-[3-(cyclopentylsulfonyl)phenyl]-3-(3-pyridinyl)-2-propenamide;
N-[4-ethoxy-3-(4-morpholinylsulfonyl)phenyl]-3-(3-pyridinyl)-2-propenamide;
N-[2-(1-methylethoxy)-5-(4-morpholinylsulfonyl)phenyl]-3-(3-pyridinyl)-2-propenamide;
N-[2-ethoxy-5-(4-morpholinylsulfonyl)phenyl]-3-(3-pyridinyl)-2-propenamide;
N-[5-[(hexahydro-1Hazepin-1-yl)sulfonyl]-2-(2,2,2-trifluoroethoxy)phenyl]-3-(3-pyridinyl)-2-propenamide;
N-[5-[(diethylamino)sulfonyl]-2-(4-morpholinyl)phenyl]-3-(3-pyridinyl)-2-propenamide;
N-[3-[[(3-chlorophenyl)amino]sulfonyl]-4-methylphenyl]-3-(3-pyridinyl)-2-propenamide;
N-[3-[[(4-chlorophenyl)amino]sulfonyl]-4-methylphenyl]-3-(3-pyridinyl)-2-propenamide;
3-(3-pyridinyl)-N-[4-[[(tetrahydro-1,1-dioxido-3-thienyl)amino]sulfonyl]phenyl]-2-propenamide;
3-(3-pyridinyl)-N-[3-[[[3-(trifluoromethyl)phenyl]amino]sulfonyl]phenyl]-2-propenamide;
or 3-(3-pyridinyl)-N-[1,4,5,6-tetrahydro-5-[(4-methylphenyl)sulfonyl]pyrrolo[3,4-c]pyrazol-3-yl]-2-propenamide.

23 more elements

Facts

Application

14/115,623Filed 2 Sep 2011 · us provisional application

Priority

4 May 2011

Published

US 2014/0275057 A118 Sep 2014

Granted

27 Oct 2015

Term ends

Not estimatedThe source records don’t support an estimate.

Classification43 codes

C07D 213/56
Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals: amides
A61K 31/4406
Non condensed pyridines; Hydrogenated derivatives thereof: only substituted in position 3, e.g. zimeldine
A61K 31/4439
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone