Small-molecule modulators of Trp-p8 activity
AssigneeDendreon Corporation
InventorsOfir Moreno, Sateesh Natarajan, David F. Duncan
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Abstract
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.
Claims11
A method for treatment of benign prostatic hyperplasia (BPH), an enlarged prostate, acute urinary retention, or symptoms thereof or reducing prostate size in a mammal comprising administering to a mammal in need of such treatment an effective amount of a compound of Formula I-B:
- wherein
- R1 is selected from H, alkyl, heteroalkyl, aryl, and arylalkyl;
- R2a is selected from aryl, alkyl, heteroalkyl, and arylalkyl;
- R3 is selected from alkyl, heteroalkyl, and arylalkyl;
- R4 is selected from H, alkyl, heteroalkyl, and arylalkyl;
- and
- R3 and R4 together with the nitrogen group form an aliphatic amine;
- or a pharmaceutically acceptable salt thereof.
A method of preparing a pharmaceutical composition useful for treating benign prostatic hyperplasia (BPH), comprising mixing a compound of Formula I-B:
- wherein
- R1 is selected from H, alkyl, heteroalkyl, aryl, and arylalkyl;
- R2a is selected from aryl, alkyl, heteroalkyl, and arylalkyl;
- R3 is selected from alkyl, heteroalkyl, and arylalkyl;
- R4 is selected from H, alkyl, heteroalkyl, and arylalkyl;
- and
- R3 and R4 together with the nitrogen group form an aliphatic amine;
- or a pharmaceutically acceptable salt thereof,
- with a pharmaceutically acceptable carrier or agent.
Dependencies are inferred from the claim text.