Biphenyl compounds useful as muscarinic receptor antagonists

A compound of formula I:

• wherein:
• a is 0 or an integer of from 1 to 5;
• each R1 is independently selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (3-6C)cycloalkyl, cyano, halo, —OR1a, —C(O)OR1b, —SR1c, —S(O)R1d, —S(O)2R1e, —NR1fR1g, —NR1hS(O)2R1i, and —NR1jC(O)R1k;
• where each of R1a, R1b, R1c, R1d, R1e, R1f, R1g, R1h, R1i, R1j, and R1k is independently hydrogen, (1-4C)alkyl or phenyl(1-4C)alkyl;
• b is 0 or an integer of from 1 to 4;
• each R2 is independently selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (3-6C)cycloalkyl, cyano, halo, —OR2a, —C(O)OR2b, —SR2c, —S(O)R2d, —S(O)2R2e, —NR2fR2g, —NR2hS(O)2R2i, and NR2jC(O)R2k;
• where each of R2a, R2b, R2c, R2d, R2e, R2f, R2g, R2h, R2i, R2j, and R2k is independently hydrogen, (1-4C)alkyl or phenyl(1-4C)alkyl;
• W represents O or NWa, where Wa is hydrogen or (1-4C)alkyl;
• c is 2 and the R3 groups are at the 2 and 6-positions on the piperidine ring and are joined to form an ethylene bridge;
• d and fare independently 0 or an integer from 1 to 10, provided that the number of contiguous atoms in the shortest chain between the two nitrogen atoms is in the range of from 7 to 17;
• Q is selected from:
• where RQa and RQb are independently selected from hydrogen, (1-4C)alkyl, and (3-6C)cycloalkyl, or are taken together to form (2-4C)alkylene or (2-3C)alkenylene;
• Y is selected from:
• where:
• R4 is selected from hydrogen, (1-4C)alkyl, (3-4C)cycloalkyl, —C(O)(1-4C)alkyl, -(1-4C)alkyleneC(O)OR4a, —C(O)heterocyclyl, —C(O)CH(NH2)(1-4C)alkyleneX, -(1-4C)alkyleneC(O)X′, —C(O)(1-4C)alkyleneX′, and —S(O)2(1-4C)alkyleneX′;
• where X is a nitrogen-containing substituent selected from —NR4bR4c and heteroaryl;
• X′ is a nitrogen-containing substituent selected from —NR4dR4e and heterocyclyl;
• R4a is hydrogen or (1-4C)alkyl;
• each of R4b, R4c, R4d and R1e independently represents hydrogen, (1-4C)alkyl, (3-6C)cycloalkyl or hydroxyphenyl, and where (1-4C)alkyl is unsubstituted or substituted by 1 or 2 substituents independently selected from amido, cyano, furyl, hydroxyl, and methylimidazolyl;
• the heterocyclyl contains 1 or 2 nitrogen atoms, and is unsubstituted or substituted by 1 or 2 substituents independently selected from hydroxyl, amido, (1-4C)alkoxy, oxo, —S(O)2(1-4C)alkyl, —(CH2)O(1-4C)alkyl, -(1-4C)alkyleneOH, —NR4fR4g and —C(O)NR4hR4i, where each of R4f, R4g, R4h and R4i independently represents hydrogen or (1-4C)alkyl;
• and the heteroaryl contains 1 or 2 nitrogen atoms;
• Z is selected from (1-3C)alkylene, —C(O)(1-3C)alkylene, (1-3C)alkyleneC(O)—, —SO2—, —SO2(1-3C)alkylene and (1-3C)alkyleneSO2—;
• where the alkylene group in any Z is optionally substituted with 1 or 2 substituents independently selected from (1-4C)alkyl and —NRZaRZb;
• wherein RZa and RZb are independently selected from hydrogen and (1-4C)alkyl;
• p is 0, 1 or 2;
• each R5 independently represents (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (3-6C)cycloalkyl, cyano, nitro, halo, N,N-di(1-4C)alkylamino(2-4C)alkoxy, —OR5a, —C(O)OR5b, —SR5c, —S(O)R5d, —S(O)2R5e or each of R5a, R5b, R5c, R5d, R5e, R5f and R5g is independently hydrogen, (1-4C)alkyl, (3-6C)cycloalkyl, phenyl or phenyl(1-4C)alkyl, wherein each phenyl group is unsubstituted or substituted by 1 or 2 substituents independently selected from halo, (1-4C)alkyl and (1-4C)alkoxy;
• and
• R6 is selected from hydrogen, (1-4C)alkyl, (1-4C)alkyleneNR6aR6b, and phenyl, each of R6a and R6b is independently hydrogen or (1-4C)alkyl;
• or R6 is taken together with R5 to form a ring having 1 to 2 oxygen atoms, where said ring is unsubstituted or substituted by 1 or 2 (1-4C)alkyl substituents;
• q is 0 or an integer from 1 to 3;
• r is 0 or an integer from 1 to 4;
• each R7 independently represents fluoro or (1-4C)alkyl;
• R8 is selected from hydrogen, —OH, -(1-4C)alkyleneOH, —NR8aR8b, —C(O)NR8aR8b, and —CH2C(O)NR8aR8b, where R8a and R8b are independently selected from hydrogen, (1-4C)alkyl, hydroxy, (1-4C)alkoxy, (1-4C)alkyleneOR8c, (3-6C)cycloalkyl, phenyl optionally substituted with hydroxy, and (1-4C)alkyleneC(O)NR8dR8e, where said (3-6C)cycloalkyl is unsubstituted or substituted with 1 or 2 (1-6C)alkyl or —NR8dR8e groups, and where each of R8c, R8d and R8e is independently hydrogen or (1-4C)alkyl;
• or R8a is taken together with R8b to form a 3-7 membered ring, optionally substituted with hydroxyl;
• R9 is selected from hydrogen, (1-4C)alkyl, and -(1-4C)alkyleneOH;
• and
• R10 is selected from (1-4C)alkyl, -(1-4C)alkyleneOH, (3-6C)cycloalkyl, -(1-4C)alkylene(3-6C)cycloalkyl, and (1-4C)alkyleneC(O)NR10aR10b, where R10a and R10b are independently hydrogen or (1-4C)alkyl;
• or R9 and R10 are taken together to form a ring selected from piperazinone, morpholine, and piperazine;
• and said piperazine is substituted with (R10c)w where w is 0 or an integer from 1 to 3 and each R10c is independently selected from (1-4C)alkyl, phenyl and benzyl, optionally substituted with 1 to 5 fluoro substituents, or two R10c groups are joined to form (1-3C)alkylene;
• wherein each alkyl and alkoxy group in R1, R1a-1k, R2, R2a-2k, R5, R5a-5g, R6, R6a-b, and R8a-e is optionally substituted with 1 to 5 fluoro substituents;
• or a pharmaceutically acceptable salt or stereoisomer thereof.