Diaminopyrimidines as P2X₃and P2X_2/3antagonists

摘要

Compounds and methods for treating diseases mediated by a P2X3 and/or a P2X2/3 receptor antagonist, the methods comprising administering to a subject in need thereof an effective amount of a compound of formula (I):;
or a pharmaceutically acceptable salt, solvate or prodrug thereof,
wherein D, X, Y, R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein.

主权项

1. A method for relieving pelvic hypersensitivity, said method comprising administering to a subject in need thereof an effective amount of a compound of formula (I):or a pharmaceutically acceptable salt thereof,wherein:
X is: —CH2—; —O—; —C(O)—; —CHOH—; —S(O)n—; or —NRc— wherein n is from 0 to 2 and Rc is hydrogen or alkyl; Y is: hydrogen; or —NRdRe wherein one of Rd and Re is hydrogen, and the other is: hydrogen; alkyl; cycloalkyl; cycloalkylalkyl; haloalkyl; haloalkoxy; hydroxyalky; alkoxyalkyl; acetyl; alkylsulfonyl; alkylsulfonylalkyl; aminocarbonyloxyalkyl; hydroxycarbonylalkyl; hydroxyalkyloxycarbonylalkyl; aryl; aralkyl; arylsulfonyl; heteroaryl; heteroarylalkyl; heteroarylsulfonyl; heterocyclyl; or heterocyclylalkyl; D is an optional oxygen; R1 is: alkyl; alkenyl; cycloalkyl; cycloalkenyl; halo; haloalkyl; hydroxyalkyl; or alkoxy; R2, R3 , R4 and R5 each independently is: hydrogen; alkyl; alkenyl; amino; halo; amido; haloalkyl; alkoxy; hydroxy; haloalkoxy; nitro; hydroxyalkyl; alkoxyalkyl; hydroxyalkoxy; alkynylalkoxy; alkylsulfonyl; arylsulfonyl; cyano; aryl; heteroaryl; heterocyclyl; heterocyclylalkoxy; aryloxy; heteroaryloxy; aralkyloxy; heteroaralkyloxy; optionally substituted phenoxy; —(CH2)m—(Z)n—(CO)—Rf or —(CH2)m—(Z)n—SO2—(NRg)n—Rf where m and n each independently is 0 or 1, Z is O or NRg, Rf is hydrogen, alkyl, hydroxy, alkoxy, amino, hydroxyalkyl or alkoxyalkyl, and each Rg is independently hydrogen or alkyl; or R3 and R4 may together form an alkylene dioxy; or R3 and R4 together with the atoms to which they are attached may form a five or six-membered ring that optionally includes one or two heteroatoms selected from O, S and N; or R2 and R3 may together form an alkylene dioxy; or R2 and R3 together with the atoms to which they are attached may form a five or six-membered ring that optionally includes one or two heteroatoms selected from O, S and N; R6 is: hydrogen; alkyl; halo; haloalkyl; amino; or alkoxy; and one of R7 and R8 is hydrogen, and the other is: hydrogen; alkyl; cycloalkyl; cycloalkylalkyl; haloalkyl; haloalkoxy; hydroxyalky; alkoxyalkyl; acetyl; alkylsulfonyl; alkylsulfonylalkyl; aminocarbonyloxyalkyl; hydroxycarbonylalkyl; hydroxyalkyloxycarbonylalkyl; aryl; aralkyl; arylsulfonyl; heteroaryl; heteroarylalkyl; heteroarylsulfonyl; heterocyclyl; or heterocyclylalkyl.