US 2011/0237528 A1Published application

Compositions and methods comprising imidazole and triazole derivatives

AssigneeInstitute for OneWorld Health

InventorsGraham Peter Jones, Kevin James Doyle

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Abstract

The present invention relates to compositions and methods for treating a disease in an animal, which disease is responsive to inhibiting of functional cystic fibrosis transmembrane conductance regulator (CFTR) polypeptide by administering to a mammal in need thereof an effective amount of a compound defined herein (including those compounds set forth in Tables 1-3 or encompassed by formulas (I), (IA), (IB), (II), and (III)) or compositions thereof, thereby treating the disease. The present invention particularly, relates to a method of treating diarrhea and polycystic kidney disease.

Claims35

Dependent claims

A compound of formula:

wherein:
Y is N or CH;
X is
alk is selected from the group consisting of alkylene and substituted alkylene;
R1 is selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, alkoxy, substituted alkoxy, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, cycloalkyloxy, substituted cycloalkyloxy, cycloalkenyl, substituted cycloalkenyl, cycloalkenyloxy, substituted cycloalkenyloxy, heterocyclic, substituted heterocyclic, heterocyclyloxy, substituted heterocyclyloxy, aryloxy and substituted aryloxy;
R2 is selected from the group consisting of hydrogen, —OR9, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl;
or, R1 and R2 together with the atoms bound thereto, form a heterocycle or substituted heterocycle;
R3 and R5 are each independently hydrogen, halo, hydroxyl, aminocarbonyl, and sulfonylamino;
R4 and R6 are each independently selected from the group consisting of hydrogen, hydroxyl, aminocarbonyl, sulfonylamino, alkoxy, —OC(O)-alkyl, —OC(O)-substituted alkyl, —OC(O)-aryl, —OC(O)-substituted aryl, —OC(O)-heteroaryl, —OC(O)-substituted heteroaryl, —OC(O)-cycloalkyl, —OC(O)-substituted cycloalkyl, —OC(O)-heterocyclic and —OC(O)-substituted heterocyclic;
R7 and R8 are each independently selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclic and substituted heterocyclic;
R9 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl and substituted cycloalkyl;
and
q is 0 or 1;
or a pharmaceutically acceptable salt, isomer, prodrug or tautomer thereof;
wherein said compound exhibits at least one of the following:
a) an IC50 of less than 30 μM in the T84 assay;
b) a greater than 30% inhibition at 20 μM in the FRT assay;
c) a greater than 35% inhibition at 50 μM in a T84 assay, provided that the compound does not have an IC50 greater than 30 μM;
or
d) an IC50 of less than 55 μM in the CHO-CFTR assay.

17 more elements

A compound selected from the group consisting of:

N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-N-methyl-1H-1,2,4-triazole-3-carboxamide;
N-benzhydryl-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3-(trifluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-methyl-N-(3-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-methyl-N-(4-(trifluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(1-(4-fluorophenyl)ethyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dibromo-4-hydroxyphenyl)-N-(3-methoxybenzyl)-1H-imidazole-4-carboxamide;
(1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazol-3-yl)(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)methanone;
(4-benzylpiperidin-1-yl)(1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazol-3-yl)methanone;
(4-benzylpiperidin-1-yl)(1-(3,5-dibromo-4-hydroxyphenyl)-1H-imidazol-4-yl)methanone;
1-(3,5-dichloro-4-hydroxyphenyl)-N-methyl-N-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-chlorobenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-N-methyl-1H-1,2,4-triazole-3-carboxamide;
N-(3-chloro-4-fluorobenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3-fluoro-5-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
N-(biphenyl-3-ylmethyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3-(dimethylamino)benzyl)-1H-1,2,4-triazole-3-carboxamide;
N-(5-chloro-2-fluorobenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-isopropoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-fluoro-3-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
N-(2-chlorobenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,3-diphenylpropyl)-1H-1,2,4-triazole-3-carboxamide;
N-(1-(4-bromophenyl)ethyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
N-((4-chlorophenyl)(phenyl)methyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(2-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,5-dichlorobenzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-dichlorobenzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3-(piperidin-1-yl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-(5-(trifluoromethyl)pyridin-2-yl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(2-fluoro-5-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide,
1-(3,5-dichloro-4-hydroxyphenyl)-N-(2-(difluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-difluorobenzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4,5-trifluorobenzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(2,2-diphenylethyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-(piperidin-1-yl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
N-(1H-pyrazol-1-yl)benzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
N-(3-chlorobenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-chlorobenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,3-dimethyl-2-oxobutyl)-1H-1,2,4-triazole-3-carboxamide;
N-allyl-N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
N-benzyl-1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,3-dimethylbutyl)-1H-1,2,4-triazole-3-carboxamide;
4-(3-(bis(3,5-difluorophenyl)(hydroxy)methyl)-1H-1,2,4-triazol-1-yl)-2,6-dichlorophenol;
4-(3-(bis(3-chlorophenyl)(hydroxy)methyl)-1H-1,2,4-triazol-1-yl)-2,6-dichlorophenol;
4-(3-(bis(3-fluorophenyl)(hydroxy)methyl)-1H-1,2,4-triazol-1-yl)-2,6-dichlorophenol;
4-(3-(bis(3,4-difluorophenyl)(hydroxy)methyl)-1H-1,2,4-triazol-1-yl)-2,6-dichlorophenol;
4-(3-(1,3-bis(4-fluorophenyl)-2-hydroxypropan-2-yl)-1H-1,2,4-triazol-1-yl)-2,6-dichlorophenol;
4-(3-(bis(3-chloro-5-fluorophenyl)(hydroxy)methyl)-1H-1,2,4-triazol-1-yl)-2,6-dichlorophenol;
4-(3-(bis(4-tert-butylphenyl)(hydroxy)methyl)-1H-1,2,4-triazol-1-yl)-2,6-dichlorophenol;
4-(3-(1,3-bis(2-fluorophenyl)-2-hydroxypropan-2-yl)-1H-1,2,4-triazol-1-yl)-2,6-dichlorophenol;
N-(4-(3,5-bis(trifluoromethyl)phenoxy)benzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-(4-(dimethylamino)phenoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-(3-(dimethylamino)phenoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-(3,4,5-trifluorophenoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-(4-(trifluoromethoxy)phenoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-(4-fluoro-3-(trifluoromethyl)phenoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-(4-tert-butylphenoxy)benzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-(3-(pyrrolidin-1-yl)phenoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-(4-chloro-3-(trifluoromethyl)phenoxy)benzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-(4-(benzyloxy)-3-fluorophenoxy)benzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-(4-(benzyloxy)-3-chlorophenoxy)benzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-(4-(benzyloxy)-3,5-dichlorophenoxy)benzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(2-(3,5-dimethylisoxazol-4-yl)ethyl)-1H-1,2,4-triazole-3-carboxamide;
N-benzyl-1-(3,5-dichloro-4-hydroxyphenyl)-N-(pyridin-3-ylmethyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-(4-(hydroxymethyl)phenoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,3-dimethylbutyl)-N-(3-(trifluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,3-dimethylbutyl)-N-(pyridin-3-ylmethyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,3-dimethylbutyl)-N-(3-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
N-benzyl-1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
N-benzyl-1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-isopropylbenzyl)-1H-1,2,4-triazole-3-carboxamide;
N-benzyl-N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
N-benzyl-1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-dichlorobenzyl)-1H-1,2,4-triazole-3-carboxamide;
N-benzyl-1-(3,5-dichloro-4-hydroxyphenyl)-N-(3-(trifluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
N-benzyl-1-(3,5-dichloro-4-hydroxyphenyl)-N-(3-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-ethyl-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-ethyl-N-(4-isopropylbenzyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-N-ethyl-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-ethyl-N-(3-(trifluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-ethyl-N-(3-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-phenoxybenzyl)-N-(pyridin-3-ylmethyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-isopropylbenzyl)-N-(pyridin-3-ylmethyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-N-(pyridin-3-ylmethyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(pyridin-3-ylmethyl)-N-(3-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-isopropyl-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-isopropyl-N-(4-isopropylbenzyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-N-isopropyl-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-dichlorobenzyl)-N-isopropyl-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-isopropyl-N-(3-(trifluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
N-allyl-1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
N-allyl-1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-isopropylbenzyl)-1H-1,2,4-triazole-3-carboxamide;
N-allyl-1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-dichlorobenzyl)-1H-1,2,4-triazole-3-carboxamide;
N-allyl-1-(3,5-dichloro-4-hydroxyphenyl)-N-(3-(trifluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
N-allyl-1-(3,5-dichloro-4-hydroxyphenyl)-N-(3-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,3-dimethylbutyl)-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,3-dimethylbutyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-dichlorobenzyl)-N-(3,3-dimethylbutyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-dichlorobenzyl)-N-ethyl-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-dichlorobenzyl)-N-(pyridin-3-ylmethyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(pyridin-3-ylmethyl)-N-(3-(trifluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-dichlorobenzyl)-N-(2,5,8,11-tetraoxatridecan-13-yl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-phenoxybenzyl)-N-(2,5,8,11-tetraoxatridecan-13-yl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-N-(3-(trifluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-dichlorobenzyl)-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(2,5,8,11-tetraoxatridecan-13-yl)-N-(3-(trifluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-N-(1-phenyl-2,5,8,11,14,17-hexaoxanonadecan-19-yl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-N-(2,5,8,11,14,17,20,23-octaoxapentacosan-25-yl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-N-(2,5,8,11,14-pentaoxahexadecan-16-yl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-N-(2,5,8,11-tetraoxatridecan-13-yl)-1H-1,2,4-triazole-3-carboxamide;
N-(2,5,8,11,14,17,20,23-octaoxapentacosan-25-yloxy)-1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
N-(2,5,8,11-tetraoxatridecan-13-yloxy)-1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-methoxy-N-(3-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-methoxy-N-(3-(trifluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-dichlorobenzyl)-N-methoxy-1H-1,2,4-triazole-3-carboxamide;
N-(4-tert-butylbenzyl)-1-(3,5-dichloro-4-hydroxyphenyl)-N-methoxy-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4-isopropylbenzyl)-N-methoxy-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-methoxy-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-ethoxy-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-hydroxy-N-(3-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4,4-dimethyl-3-oxo-1-(3-(trifluoromethyl)phenyl)pentan-2-yl)-1H-1,2,4-triazole-3-carboxamide;
1-(3,5-dichloro-4-hydroxyphenyl)-N-(4,4-dimethyl-3-oxo-1-(3-(trifluoromethoxy)phenyl)pentan-2-yl)-1H-1,2,4-triazole-3-carboxamide;
and
1-(3,5-dichloro-4-hydroxyphenyl)-N-(1-(4-isopropylphenyl)-4,4-dimethyl-3-oxopentan-2-yl)-1H-1,2,4-triazole-3-carboxamide;
or a pharmaceutically acceptable salt, isomer, prodrug or tautomer thereof.

123 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/119,941Filed 16 Sep 2009
Priority: 19 Sep 2008
Published: 29 Sep 2011
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 249/10
1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond…
A61P 1/12
Drugs for disorders of the alimentary tract or the digestive system: antidiarrhoeals
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/06
Drugs for disorders of the cardiovascular system: antiarrhythmics

Family

Application61/098,596Us provisional application · filed 19 Sep 2008
Application61/173,120Us provisional application · filed 27 Apr 2009
US 2011/0237528 A1This patent

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

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Abstract

A compound of formula:

wherein:
Y is N or CH;
X is
alk is selected from the group consisting of alkylene and substituted alkylene;
R1 is selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, alkoxy, substituted alkoxy, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, cycloalkyloxy, substituted cycloalkyloxy, cycloalkenyl, substituted cycloalkenyl, cycloalkenyloxy, substituted cycloalkenyloxy, heterocyclic, substituted heterocyclic, heterocyclyloxy, substituted heterocyclyloxy, aryloxy and substituted aryloxy;
R2 is selected from the group consisting of hydrogen, —OR9, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl;
or, R1 and R2 together with the atoms bound thereto, form a heterocycle or substituted heterocycle;
R3 and R5 are each independently hydrogen, halo, hydroxyl, aminocarbonyl, and sulfonylamino;
R4 and R6 are each independently selected from the group consisting of hydrogen, hydroxyl, aminocarbonyl, sulfonylamino, alkoxy, —OC(O)-alkyl, —OC(O)-substituted alkyl, —OC(O)-aryl, —OC(O)-substituted aryl, —OC(O)-heteroaryl, —OC(O)-substituted heteroaryl, —OC(O)-cycloalkyl, —OC(O)-substituted cycloalkyl, —OC(O)-heterocyclic and —OC(O)-substituted heterocyclic;
R7 and R8 are each independently selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclic and substituted heterocyclic;
R9 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl and substituted cycloalkyl;
and
q is 0 or 1;
or a pharmaceutically acceptable salt, isomer, prodrug or tautomer thereof;
wherein said compound exhibits at least one of the following:
a) an IC50 of less than 30 μM in the T84 assay;
b) a greater than 30% inhibition at 20 μM in the FRT assay;
c) a greater than 35% inhibition at 50 μM in a T84 assay, provided that the compound does not have an IC50 greater than 30 μM;
or
d) an IC50 of less than 55 μM in the CHO-CFTR assay.

17 more elements

Facts

Application

13/119,941Filed 16 Sep 2009

Priority

19 Sep 2008

Published

29 Sep 2011

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 249/10
1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond…
A61P 1/12
Drugs for disorders of the alimentary tract or the digestive system: antidiarrhoeals
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/06
Drugs for disorders of the cardiovascular system: antiarrhythmics