US 8,076,376 B2Granted

Aniline sulfonamide derivatives and their uses

OwnerJay P. Powers, Xiao He +3inventors

InventorsJay P. Powers, Xiao He, Dustin McMinn, Yosup Rew, Daqing Sun

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Abstract

Aniline sulfonamide derivatives according to formula I have therapeutic utility, particularly in the treatment of diabetes, obesity and related conditions and disorders: where R1, R2, R3, R4, R5, R6, and L are set forth in the description.

Claims23

Dependent claims

A compound having the formula (I):

or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
R1, R2, and R3, together with the carbon atom to which they are attached, are an (S)-trifluoromethyl carbinol group of the formula:
or an (R)-trifluoromethyl carbinol group of the formula:
R4 is a member selected from the group consisting of hydrogen, halogen, (C1-C8)alkyl and (C3-C8)cycloalkyl;
R5 is selected from the group consisting of hydrogen, —OH, halogen, (C1-C8)alkyl, (C1-C8)haloalkyl, (C2-C8)heteroalkyl, (C3-C8)cycloalkyl, (C3-C8)heterocycloalkyl, C(O)R′, C(O)NR′2, NR′2, NR′C(O)R′, CN, NO2, aryl, and heteroaryl;
R6 is aryl or heteroaryl, or R6 optionally may be combined with R5 to form a 5- to 6-membered fused ring containing L, the nitrogen atom to which L is attached, and the sulfur atom to which R6 is attached;
L is selected from the group consisting of a direct bond, (C1-C4)alkylene and (C2-C4)alkenylene;
wherein any cycloalkyl portion, heterocycloalkyl portion, aryl or heteroaryl portion is optionally substituted with from one to four members selected from the group consisting of halogen, —CN, —NO2, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C1-C8)alkoxy, (C1-C8)haloalkyl, (C2-C8)hydroxyalkyl, —C(O)R′, —C(O)OR′, —NR′C(O)OR″, —OR′, —SR′, —OC(O)R′, —C(O)N(R′)2, —S(O)R″, —SO2R″, —SO2N(R′)2, —N(R′)2 and —NR′C(O)R′;
wherein each occurrence of R′ is independently H or an unsubstituted member selected from the group consisting of (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C1-C4)alkoxy(C1-C4) alkyl, (C1-C8)haloalkyl, (C2-C8)hydroxyalkyl, (C3-C8)cycloalkyl, (C3-C8)heterocycloalkyl, heteroaryl, aryl, (C3-C8)cycloalkyl(C1-C6)alkyl, (C3-C8) heterocycloalkyl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, and aryl(C1-C6)alkyl,
wherein two R′ groups, when attached to the same nitrogen atom, can be combined with the nitrogen atom to which they are attached to form a heterocycle or heteroaryl group;
and
wherein each occurrence of R″ is independently an unsubstituted member selected from the group consisting of (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C8)haloalkyl, (C2-C8)hydroxyalkyl, (C3-C8)cycloalkyl, (C3-C8)heterocycloalkyl, heteroaryl, aryl, (C3-C8)cycloalkyl(C1-C6)alkyl, heterocyclyl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl and aryl(C1-C6)alkyl.

9 more elements

A compound selected from the group consisting of:

N-isopropyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2-chloro-N-isopropyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2,3-dichloro-N-isopropyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2-fluoro-N-isopropyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2,6-dichloro-N-isopropyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2-chloro-4-cyano-N-isopropyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2,5-dichloro-N-isopropyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
tert-butyl-2,5-dichloro-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2-chloro-N-(cyclopropylmethyl)-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2,5-dichloro-N-isobutyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2-chloro-N-isopropyl-5-nitro-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
5-amino-2-chloro-N-isopropyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
5-bromo-2-chloro-N-isopropyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2-chloro-N-ethyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2-chloro-N-methyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2-chloro-N-(2-chloro-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl)-N -isopropylbenzenesulfonamide;
2-chloro-N-(2-chloro-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl)-N -ethylbenzenesulfonamide;
2-chloro-N-(1-fluoropropan-2-yl)-N-(4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)pheny)benzenesulfonamide;
2,5-dichloro-N-(2,2,2-trifluoroethyl)-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2,3-dichloro-N-(2,2,2-trifluoroethyl)-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2-chloro-N-(2,2,2-trifluoroethyl)-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2,3-dichloro-N-cyclopropyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2,5-dichloro-N-cyclobutyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2,5-dichloro-N-phenyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide;
2-cyclopropyl-N-isopropyl-N-[4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide, and
pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof.

23 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/490,143Filed 21 Jul 2006 · us provisional application
Priority: 22 Jul 2005
Published: US 2007/0021502 A125 Jan 2007
Granted: 13 Dec 2011
Term ends: Not estimatedThe source records don’t support an estimate.

Classification23 codes

C07C 311/21
Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings: having the nitrogen atom of at least…
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 3/06
Drugs for disorders of the metabolism: antihyperlipidemics
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics

Family

Application60/701,476Us provisional application · filed 22 Jul 2005
US 2007/0021502 A1Pre-grant publication · published 25 Jan 2007
US 8,076,376 B2This patent

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

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Abstract

A compound having the formula (I):

or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
R1, R2, and R3, together with the carbon atom to which they are attached, are an (S)-trifluoromethyl carbinol group of the formula:
or an (R)-trifluoromethyl carbinol group of the formula:
R4 is a member selected from the group consisting of hydrogen, halogen, (C1-C8)alkyl and (C3-C8)cycloalkyl;
R5 is selected from the group consisting of hydrogen, —OH, halogen, (C1-C8)alkyl, (C1-C8)haloalkyl, (C2-C8)heteroalkyl, (C3-C8)cycloalkyl, (C3-C8)heterocycloalkyl, C(O)R′, C(O)NR′2, NR′2, NR′C(O)R′, CN, NO2, aryl, and heteroaryl;
R6 is aryl or heteroaryl, or R6 optionally may be combined with R5 to form a 5- to 6-membered fused ring containing L, the nitrogen atom to which L is attached, and the sulfur atom to which R6 is attached;
L is selected from the group consisting of a direct bond, (C1-C4)alkylene and (C2-C4)alkenylene;
wherein any cycloalkyl portion, heterocycloalkyl portion, aryl or heteroaryl portion is optionally substituted with from one to four members selected from the group consisting of halogen, —CN, —NO2, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C1-C8)alkoxy, (C1-C8)haloalkyl, (C2-C8)hydroxyalkyl, —C(O)R′, —C(O)OR′, —NR′C(O)OR″, —OR′, —SR′, —OC(O)R′, —C(O)N(R′)2, —S(O)R″, —SO2R″, —SO2N(R′)2, —N(R′)2 and —NR′C(O)R′;
wherein each occurrence of R′ is independently H or an unsubstituted member selected from the group consisting of (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C1-C4)alkoxy(C1-C4) alkyl, (C1-C8)haloalkyl, (C2-C8)hydroxyalkyl, (C3-C8)cycloalkyl, (C3-C8)heterocycloalkyl, heteroaryl, aryl, (C3-C8)cycloalkyl(C1-C6)alkyl, (C3-C8) heterocycloalkyl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, and aryl(C1-C6)alkyl,
wherein two R′ groups, when attached to the same nitrogen atom, can be combined with the nitrogen atom to which they are attached to form a heterocycle or heteroaryl group;
and
wherein each occurrence of R″ is independently an unsubstituted member selected from the group consisting of (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C8)haloalkyl, (C2-C8)hydroxyalkyl, (C3-C8)cycloalkyl, (C3-C8)heterocycloalkyl, heteroaryl, aryl, (C3-C8)cycloalkyl(C1-C6)alkyl, heterocyclyl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl and aryl(C1-C6)alkyl.

9 more elements

Facts

Application

11/490,143Filed 21 Jul 2006 · us provisional application

Priority

22 Jul 2005

Published

US 2007/0021502 A125 Jan 2007

Granted

13 Dec 2011

Term ends

Not estimatedThe source records don’t support an estimate.

Classification23 codes

C07C 311/21
Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings: having the nitrogen atom of at least…
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 3/06
Drugs for disorders of the metabolism: antihyperlipidemics
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics