Small-molecule modulators of hepatocyte growth factor / scatter factor activities
AssigneeNorth Shore-Long Island Jewish Health System
InventorsSivaram Pillarisetti, Itzhak D. Goldberg
Life of this patent
Estimating the term…
Abstract
The invention is directed to small organic molecules having the ability to mimic or agonize hepatocyte growth factor/scatter factor (HGF/SF) activity, or inhibit or antagonize HGF/SF activity, the former useful for promoting, for example, vascularization of tissues or organs for promoting wound or tissue healing, or augmenting or restoring blood flow to ischemic tissues such as the heart following myocardial infarction. Inhibition of cellular growth or proliferation is beneficial in the treatment, for example, of inflammatory diseases such as inflammatory joint and skin diseases, and dysproliferative diseases such as cancer.
Claims6
A method for modulating HGF/SF activity in a mammal comprising administering to said mammal an effective HGF/SF activity modulating amount of a compound with the general formula I:
- wherein
- R3 and R5 are independently or together methyl, t-butyl or chloro groups;
- R1 is CO-Aryl, SO2-Aryl, CO-heteroaryl, or CO-alkyl, wherein said Aryl is phenyl, naphthyl or diphenyl, said Aryl substituted with one or more halogen, C1 to C4 alkyl, or C1 to C4 alkyloxy groups, or said heteroaryl is a 3-aryl-substituted isoxazole or a 3-aryl substituted thienyl group, or said alkyl group is a t-butyl;
- and
- R4 is CH2-Aryl, halogen, arylcarbonylvinyl or S-heteroaryl.
A method for modulating HGF/SF activity in a mammal comprising administering to said mammal an effective HGF/SF activity modulating amount of a compound selected from the group consisting of
- 3-(5-chloro-1,3-dimethyl-1H-pyrazol-4-yl)-1-(4-chlorophenyl)prop-2-en-1-one;
- [4-(2,6-dichlorobenzyl)-3,5-dimethyl-1H-pyrazol-1-yl][3-(2,6-dichlorophenyl)-5-methylisoxazol-4-yl]methanone;
- (4-(2-chloro-6-fluorobenzyl)-3,5-dimethyl-1H-pyrazole-1-yl)(3-(2,6-dichlorophenyl)-5-methylisoxazol-4-yl)methanone;
- 4-(2-chloro-6-fluorobenzyl)-1-((3,4-dichlorophenyl)sulfonyl)-3,5-dimethyl-1H-pyrazole;
- 4-(2-chloro-6-fluorobenzyl)-1,3,5-trimethyl-1H-pyrazole;
- 4-(2-chloro-6-fluorobenzyl)-3,5-dimethyl-1H-pyrazole;
- (4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)(3-(2,6-dichlorophenyl)isoxazole-4-carbohydrazide);
- 3-(4-(2,6-dichlorobenzyl)-3,5-dimethyl-1H-pyrazol-1-yl)propanenitrile;
- 3,5-di(tert-butyl)-4-(2-chloro-6-fluorobenzyl)-1H-pyrazole;
- (4-(2-chloro-6-fluorobenzyl)-3,5-dimethyl-1H-pyrazole-1-yl)(2,6-dichlorophenyl)methanone;
- 1-(4-(2-chloro-6-fluorobenzyl)-3,5-dimethyl-1H-pyrazole-1-yl)2,2-dimethylpropan-1-one;
- (4-(2-chloro-6-fluorobenzyl)-3,5-dimethyl-1H-pyrazole-1-yl)(4-chlorophenyl)methanone;
- (4-(2-chloro-6-fluorobenzyl)-3,5-dimethyl-1H-pyrazole-1-yl)(2-thienyl)methanone;
- and
- (4-chlorophenyl)(3,5-dimethyl-4-((1-methyl-1H-imidazol-2-yl)thio)-1H-pyrazol-1-yl)methanone.
A pharmaceutical composition comprising a compound with the general formula I:
- wherein
- R3 and R5 are independently or together methyl, t-butyl or chloro groups;
- R1 is CO-Aryl, SO2-Aryl, CO-heteroaryl, or CO-alkyl, wherein said Aryl is phenyl, naphthyl or diphenyl, said Aryl substituted with one or more halogen, C1 to C4 alkyl, or C1 to C4 alkyloxy groups, or said heteroaryl is a 3-aryl-substituted isoxazole or a 3-aryl substituted thienyl group, or said alkyl group is a t-butyl;
- and
- R4 is CH2-Aryl, halogen, arylcarbonylvinyl or S-heteroaryl;
- And a pharmaceutically-acceptable carrier.
Dependencies are inferred from the claim text.