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US 2009/0264471 A1Published application
Compounds, Compositions and Methods Comprising Triazole Derivatives
AssigneeInstitute for OneWorld Health
InventorsMichael Geoffrey Neil Russell, Kevin James Doyle
Life of this patent
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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 1-2 or encompassed by formulas I-II) or compositions thereof, thereby treating the disease. The present invention particularly, relates to a method of treating diarrhea and polycystic kidney disease.
Claims37
A compound of formula I:
- wherein:
- 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, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl;
- or R1 and R2 taken together with the atoms bound thereto form a heterocycle or a substituted heterocycle;
- R3 and R4 are each independently halo;
- R5 is selected from the group consisting of hydrogen and hydroxyl;
- R6 is selected from the group consisting of hydrogen, alkyl and substituted alkyl;
- and
- p is 0, 1, 2, or 3;
- or
- a pharmaceutically acceptable salt, isomer, 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;
- or
- 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.
13 more elements
A compound selected from the group consisting of:
- N-benzhydryl-3-(3,5-dibromo-4-hydroxy phenyl)-1H-1,2,4-triazole-5-carboxamide;
- (3-(3,5-dibromo-4-hydroxyphenyl)-1H-1,2,4-triazol-5-yl)(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)methanone;
- 3-(3,5-dibromo-4-hydroxyphenyl)-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-5-carboxamide;
- (4-benzylpiperidin-1-yl)(3-(3,5-dibromo-4-hydroxyphenyl)-1H-1,2,4-triazol-5-yl)methanone;
- 5-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-difluorobenzyl)-1H-1,2,4-triazole-3-carboxamide;
- 5-(3,5-dichloro-4-hydroxyphenyl)-N-(2-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
- 5-(3,5-dichloro-4-hydroxyphenyl)-N-(3-(trifluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
- 5-(3,5-dichloro-4-hydroxyphenyl)-N-(4-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
- N-benzhydryl-5-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazole-3-carboxamide;
- 5-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4,5-trifluorobenzyl)-1H-1,2,4-triazole-3-carboxamide;
- 5-(3,5-dichloro-4-hydroxyphenyl)-N-methyl-N-(3-(trifluoromethyl)benzyl)-1H-1,2,4-triazole-3-carboxamide;
- 5-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-dichlorobenzyl)-1H-1,2,4-triazole-3-carboxamide;
- 5-(3,5-dichloro-4-hydroxyphenyl)-N-(4-phenoxybenzyl)-1H-1,2,4-triazole-3-carboxamide;
- N-(4-chlorobenzyl)-5-(3,5-dichloro-4-hydroxyphenyl)-N-methyl-1H-1,2,4-triazole-3-carboxamide;
- 5-(3,5-dichloro-4-hydroxyphenyl)-N-(4-(trifluoromethoxy)benzyl)-1H-1,2,4-triazole-3-carboxamide;
- 5-(3,5-dichloro-4-hydroxyphenyl)-N-(3,4-dichlorobenzyl)-N-methyl-1H-1,2,4-triazole-3-carboxamide;
- N-(4-tert-butylbenzyl)-5-(3,5-dichloro-4-hydroxyphenyl)-N-methyl-1H-1,2,4-triazole-3-carboxamide;
- 5-(3,5-dichloro-4-hydroxyphenyl)-N-(3,5-dichlorobenzyl)-1H-1,2,4-triazole-3-carboxamide;
- (4-benzylpiperidin-1-yl)(5-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazol-3-yl)methanone;
- and
- (5-(3,5-dichloro-4-hydroxyphenyl)-1H-1,2,4-triazol-3-yl)(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)methanone
- or a pharmaceutically acceptable salt, isomer, or tautomer thereof.
19 more elements
Dependencies are inferred from the claim text.