P2X3 receptor antagonists for pain management

摘要

A compound of structural formula I: ** (See formula) ** or pharmaceutically acceptable salts and individual enantiomers and diastereomers thereof; for use in the treatment or prevention of chronic or acute pain, the treatment or control of epilepsy, or the improvement of sleep quality in a mammalian patient who needs it; wherein: A represents thienopyrazolyl, indazolyl or indolyl; B represents a bond, C1-6 alkyl, C2-6 alkenyl, C3-10 cycloalkyl, C5-10 heterocyclyl or C6-10 aryl; R1 represents H, C1-6 alkyl, halogen, (CH2) nCF3, C3-10 cycloalkyl, C (R2) 2OH, -O-, CN, (CH2) nOR2, NHC (O) R2, (CH2) C5- nheterocyclyl 10, (CH2) C6-10 naryl or C1-6 alkoxy; said alkyl, cycloalkyl, heterocyclyl and aryl optionally substituted with 1 to 3 C1-6 alkyl groups, halogen, hydroxyl, (CH2) nCF3 or CN; R2 represents H; R3 is selected from the group consisting of (CHRy) npyridyl, (CHRy) nooxyrpyridyl, (CHRy) npyrimidinyl, (CHRy) ntriazolyl, (CHRy) nphenyl, (CHRy) npyrazinyl, (CHRy) npyrazolyl, (CHRy) noxadiazol CHRy) nthiazolyl, (CHRy) nthiadiazolyl, (CHRy) nindazopyridyl ,, C1-6 alkyl and (CHRy) C3-6 cycloalkyl, all of which are optionally substituted with 1 to 3 groups of Ra, and in which Ry represents H, CF3, OH or C1-6 alkyl which is optionally substituted with 1 to 3 groups of Ra; or R2 and R3 can be combined with the nitrogen to which they are attached to form a C5-10 heterocyclyl optionally substituted with 1 to 3 groups of Ra; R4 and R5 independently represent H, (CH2) nOR2, CHF2, (CH2) C5-10 nheterocyclyl, (CH2) C6-10 naryl, C3-10 cycloalkyl, C1-6 alkoxy, C2-6 alkenyl, CF3, CF2, C (O) 1-2R2 or C1-6 alkyl; said alkyl, cycloalkyl, heterocyclyl and aryl optionally substituted with 1 to 3 groups of Ra; R6 represents hydrogen, OR2, (CH2) nCF3, halogen, C (R2) 2OR2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, (CH2) C6-10 naryl, (CH2) C5-10 n-heterocyclyl, said alkyl, cycloalkyl, aryl and heterocyclyl optionally substituted with 1 to 3 groups of Ra; Ra represents C1-6 alkyl, halogen, hydroxyl, OR2 (CH2) nCF3, -O-, C3-6 cycloalkyl, NR2C (O) R2, C (O) N (R2) 2, C (R2) 2OR2, C ( O) R2, O (CH2) nC (O) N (R2) 2, O (CH2) nC (O) OR2, C (O) C5-10 heterocyclyl, NO2, CN, N (R2) 2, C (O ) OR2, SO2R2, OR2, (CH2) C5-10 nheterocyclyl or (CH2) C6-10 naryl, said alkyl, heterocyclyl and aryl optionally substituted with 1 to 3 C1-6 alkyl groups, halogen, hydroxyl, (CH2) nCF3 or CN; and n represents from 0 to 4.