Diaminopirimidinas as modulators of P2X3 and P2X2 / 3, Pharmaceutical compositions that comprise and use in preparation of drugs for the treatment of related diseases.

摘要

Also provided are medicines that use compounds for treating Diseases mediated by P2X3 Receptor Antagonists P P2X2 / 3 and Pharmaceutical compositions containing same.Claim 1: a compound of the formula (1) or a pharmaceutically acceptable Salt thereof, in which X is - CH2 -, - O -, - S (o) n -, o - NRC; where n is 0 to 2 and RC is H or alkyl; d is a or Optional; one or two of a, e, G, J, y, and Z are n while others are CRA; or a, e, G, J, and C and Z are Ra; r1 is alkyl, cycloalkyl, alquenilo, alquinilo, cicloalquenilo, Halo, haloalquilo,Or hidroxialquilo independently; each ra is H, alkyl, amino, alquenilo, aminosulfonilo, Halo, haloalquilo, amido, Hydroxy, alkoxy, Nitro, amino, haloalcoxi, hidroxialquilo, alkoxyalkyl esters, hidroxialcoxi, alquinilalcoxi, alquilsulfonilo, arilsulfonilo, cyano, aryl, heteroaryl, heterociclilo, Heterociclilalcoxi, ariloxi, heteroariloxi, aralquiloxi, heteroaralquiloxi,Optionally substituted phenoxy; c:: C - RB -; - (CH2) M - (Z) - N - (CO) RC; - (CH2) M - (Z) - SO2 - (NRD) n - RC, where M and N are each independently 0 OR 1 Z is o or NRD, rb is H, alkyl, aryl, heteroaryl, aralquilo, heteroaralquilo, hidroxialquilo, alkoxyalkyl esters, alquilsulfonilalquilo, aminoalquilo, C Ianoalquilo, alquilsililo, cycloalkyl, cicloalquilalquilo,And heterociclilalquilo; heterocycle; RC is H, alkyl, Hydroxy, alkoxy, amino, or alkoxyalkyl Esters hidroxialquilo Rd, and each is independently H or alkyl; R4 is H, alkyl, Halo, haloalquilo, amino, or alkoxy; R7 and R8 each independently is H, alkyl, cycloalkyl, cicloalquilalquilo, Haloa Lquilo, haloalcoxi, hidroxialquilo alkoxyalkyl esters, alquilsulfonilo alquilsulfonilalquilo,,,Aminocarboniloxialquilo, hidroxicarbonilalquilo, hidroxialquiloxicarbonilalquilo, aryl, heteroaryl, aralquilo, arilsulfonilo, heteroarilalquilo, heteroarilsulfonilo, heterociclilo, heterociclilalquilo; o - (c = o) - Re, in which re is alkyl, alkoxy, cycloalkyl, cicloalcoxi, cicloalquilalquilo CIC Loalquilalcoxi, aryl, heteroaryl, ariloxi, heteroariloxi, aralquilo, aralcoxi, heteroaralquilo,Heteroaralcoxi, - (CH2) P - C (= o) - (RF - ch = CH -) - C (= o) - RF, or - ch (NH2) - RG, which RF is H, alkyl, Hydroxy, alkoxy, cicloalcoxi, cycloalkyl, aryl, cicloalquilalquilo, cicloalquilalcoxi, ariloxi, heteroaryl, heteroariloxi, aralquilo, aralcoxi, heteroaralquilo, heteroaralcoxi or amino; p is 2 or 3; RG is H, alkyl, optionally substituted hidroxialquilo, aminoalquilo, phenyl, Benzyl,Guanidinilalquilo, carboxialquilo, amidoalquilo, tioalquilo or imidazolalquilo.