| abstract |
Compounds represented by structural formula (1), or a pharmaceutically acceptable salt thereof, wherein: A<1>, A<2>, A<3> and A<4> 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; R<5>, R<7>, R<9>, R<11>, R<12> and R<14> are H, alkyl, phenyl, benzyl, -CF3 or -C2F5; R<10> is H or alkyl; R<6> and R<8> are R<5>, or optionally substituted alkyl further substituted by -OR<11>, -NR<11>R<12>, -SH, -S(O)eR<13>, -CO2R<11>, -OC(O)R<11>, -CONR<11>R<12>, -COR<11> or -NR<11>C(O)R<12>; R<13> is alkyl, phenyl, benzyl, -CF3 or -C2F5; Q is a bond, -C(O)-, -NR<17>-, -(C(R<9>)(R<10>))-, -O-, -S(O)e-, -C(X)NR<11>-, -N(R<11>)C(X)-, -N(R<11>)SO2- or -SO2N(R<11>)-; R<17> is H, alkyl, -S(O)eR<13>, -COR<11>, -CO2R<13>, -CONR<11>R<12>, allyl, -(C1-C6 alkyl)-CH=CH2, phenyl or benzyl; X is =O, =S or =N(R<12>); Y<1> is -(C(R<9>)(R<10>))m-, -G-(C(R<9>)(R<10>))m- or -(C(R<9>)(R<10>))m-G-; G represents formulas (a); (b); (c); (d); (e) or (f), with certain provisos; T is H, aryl, heterocycloalkyl, heteroaryl, cycloalkyl, -OR<11>, -N(R<11>)(R<12>), -COR<11>, -CO2R<11>, -CON(R<11>)(R<12>), -S(O)eR<13>, -NR<11>CO2R<13>, -NR<11>COR<12>, -NR<11>CON(R<12>)(R<14>) or -OC(O)N(R<11>)(R<12>); V is a bond, -S(O)e-, -O- or -N(Z<2>)-, -N(Z<2>)C(O)- or -N(Z<2>)C(S)-; Y<2> is -(C(R<9>)(R<10>))m-; Z<1> is Z<2>, -NR<11>R<12>, -OR<11> or SR<11>; Z<2> is H, alkyl, phenyl, benzyl, -CF3 or -C2F5; or Z<1> and Z<2> together are -(C(R<9>)(R<10>))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. |