Compositions and methods for the treatment of disease associated with TRP-P8 expression
View Patent ↗Provided are small-molecule Trp-p8 modulators, including Trp-p8 agonists and Trp-p8 antagonists, and compositions comprising small-molecule Trp-p8 agonists as well as methods for identifying and characterizing novel small-molecule Trp-p8 modulators and methods for decreasing viability and/or inhibiting growth of Trp-p8 expressing cells, methods for activating Trp-p8-mediated cation influx, methods for stimulating apoptosis and/or necrosis, and related methods for the treatment of diseases, including cancers such as lung, breast, colon, and/or prostate cancers as well as other diseases, such as benign prostatic hyperplasia, that are associated with Trp-p8 expression.
1. A method for decreasing the viability of a Trp-p8 expressing cell, said method comprising the step of contacting said cell with a compound of Formula IV
and pharmaceutically acceptable salts thereof, wherein
R 14 and R 15 together form a cyclic or heterocyclic group of up to 25 carbons and including the nitrogen atom.
2. The method of claim 1 wherein said cyclic or heterocyclic group is selected from the group consisting of 3-phenyl-piperidin-1-yl, 3-phenyl-pyrrolidin-1-yl, 6,7-dimethoxy-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl, and 4-pyrimidin-2-yl-piperazin-1-yl.
3. A method for inducing apoptosis and/or necrosis in a cell expressing Trp-p8, said method comprising the step of administering to said cell a compound of Formula IV
and pharmaceutically acceptable salts thereof, wherein
R 14 and R 15 together form a cyclic or heterocyclic group of up to 25 carbons and including the nitrogen atom.
4. A method for treating a disease associated with Trp-p8 expression, said method comprising the step of administering to a mammal an efficacious amount of a composition comprising a compound having the formula:
and pharmaceutically acceptable salts thereof, in combination with a pharmaceutically acceptable carrier or diluent, wherein
R 14 and R 15 together form a cyclic or heterocyclic group of up to 25 carbons and including the nitrogen atom.
5. The method of claim 4 wherein said cyclic or heterocyclic group is selected from the group consisting of 3-phenyl-piperidin-1-yl, 3-phenyl-pyrrolidin-1-yl, 6,7-dimethoxy-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl, and 4-pyrimidin-2-yl-piperazin-1-yl.