| 摘要 |
Compounds represented by structural formula (1), or a pharmaceutically acceptable salt thereof, wherein: A1, A2, A3 and A4 are methylene, -CH= or -NH-, all optionally substituted, or -N=, -O-, -S(O)e-, -C(O)- or a bond; E is phenyl or heteroaryl; W is cycloalkyl, aryl, heterocycloalkyl or heteroaryl; R5, R7, R9, R11, R12 and R14 are H, alkyl, phenyl, benzyl, -CF3 or -C2F5; R10 is H or alkyl; R6 and R8 are R5, or optionally substituted alkyl further substituted by -OR11, -NR11R12, -SH, -S(O)eR13, -CO2R11, -OC(O)R11, CONR11R12, -COR11 or -NR11C(O)R12; R13 is alkyl, phenyl, benzyl, -CF3 or C2F5; Q is a bond, -C(O)-, -NR17-, -(C(R9)(R10))-, -O-, -S(O)e-, -C(X)NR11-, N(R11)C(X)-, -N(R11)SO2- or -SO2N(R11)-; R17 is H, alkyl, -S(O)eR13, -COR11, CO2R13, -CONR11R12, allyl, -(C1-C6 alkyl)-CH=CH2, phenyl or benzyl; X is =O, =S or =N(R12); Y1 is -(C(R9)(R10))m-, -G-(C(R9)(R10))m- or -(C(R9)(R10))m-G-; G represents formulas (a); (b); (c); (d); (e) or (f), with certain provisos; T is H, aryl, heterocycloalkyl, heteroaryl, cycloalkyl, -OR11, -N(R11)(R12), COR11, -CO2R11, -CON(R11)(R12), -S(O)eR13, -NR11CO2R13, -NR11COR12, NR11CON(R12)(R14) or -OC(O)N(R11)(R12); V is a bond, -S(O)e-, -O- or -N(Z2)-, N(Z2)C(O)- or -N(Z2)C(S)-; Y2 is -(C(R9)(R10))m-; Z1 is Z2, -NR11R12, -OR11 or SR11; Z2 is H, alkyl, phenyl, benzyl, -CF3 or -C2F5; or Z1 and Z2 together are -(C(R9)(R10))u-, wherein u is 1-4; e and n are 0-2; m and p are 0-3; and r and s are 1-4; wherein cycloalkyl, heterocycloalkyl, phenyl, benzyl, aryl and heteroaryl groups are all optionally substituted; methods of treating asthma, cough, bronchospasm, inflammatory diseases, and gastrointestinal disorders with said compounds, and pharmaceutical compositions comprising said compounds are disclosed.
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