Small-molecule modulators of trp-p8 activity

A method for prophylaxis or 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-A:

• wherein A, B, C, and D are independently selected from CR2 and N;
• wherein at least one of A, B, C, and D is CR2;
• wherein R2 is a member selected from H, alkyl, heteroalkyl, aryl, halogen, and arylalkyl, R6O—, and R6S—, wherein R6 is alkyl;
• wherein when two adjacent of A, B, C, and D are C R2, the two R2's may combine to form a single aryl, cycloalkyl, or heterocycloalkyl group;
• and
• R1 is selected from H, alkyl, heteroalkyl, aryl, and arylalkyl;
• R3 is selected from alkyl, heteroalkyl, aryl, arylalkyl, —NR7C(O)—, —C(O)NR7—, —O—, —S—, —S(O)—, —S(O)2—, and —NR7—, wherein R7 is a member selected from H, alkyl, heteroalkyl, aryl, and arylalkyl;
• R4 is selected from —C(O)R8—, alkyl, arylalkyl, and heteroalkyl, wherein R8 is selected from alkyl and heteroalkyl;
• R5 is selected from H, alkyl, heteroalkyl, and arylalkyl;
• and
• R4 and R5 together with the nitrogen group form an aliphatic amine;
• or a pharmaceutically acceptable salt thereof.

A method for prophylaxis or 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;
• R2 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 for prophylaxis or 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-C:

• wherein R1 is selected from H, alkyl, heteroalkyl, aryl, and arylalkyl;
• R2 is selected from aryl, and arylalkyl;
• R3 is selected from alkyl, heteroalkyl, arylalkyl, —NHC(O)R5—, —OR5—, and —NHR5—, wherein R5 is alkyl or heteroalkyl;
• 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 for prophylaxis or 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-D:

• wherein R1 is selected from H, alkyl, heteroalkyl, aryl, and arylalkyl;
• R2 is selected from aryl, 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.