Biphenyl derivatives having adrenergic beta2 agonist activity receptor and muscarinic receptor antagonist activity

Compounds of formula I: ** ** Formula wherein: a is 0 or an integer of 1 to 3; each R1 is independently selected from alkyl (1-4C), (2-4C) alkenyl, (2-4C) alkynyl, (3-6C) cycloalkyl, cyano, halo, -OR 1a, -C (O) OR1b, -SR1c , -S (O) R1d, -S (O) 2K1C and -NR1fR1g; each of R1a, R1b, R1c, R1d, R1e, R1f and R1g is independently hydrogen, (1-4C) alkyl or phenyl- (1-4C) alkyl; b is 0 or an integer of 1 to 3; each R2 is independently selected from alkyl (1-4C), (2-4C) alkenyl, (2-4C) alkynyl, (3-6C) cycloalkyl, cyano, halo, -OR2a, -C (O) OR2b, -SR2c , -S (O) R2d, -S (O) 2R2e and -NR2fR2g. each of R2a, R2b, R2c, R2d, R2e, R 3f and R 2g is independently hydrogen, (1-4C) alkyl or phenyl- (1-4C) alkyl; W is attached at the 3 or 4 position relative to the nitrogen atom in the piperidine ring and represents O or NWa; Wa is hydrogen or (1-4C) alkyl; c is 0 or an integer of 1 to 4; each R3 is independently selected from alkyl (1-4C), (2-4C) alkenyl, (2-4C) alkynyl, (3-6C) cycloalkyl, cyano, halo, -OR 3a, -C (O) OR3b, -SR3c , -S (O) R3d, -S (O) 2R3e and -NR3fR3g; or two R3 groups are joined to form alkylene (1-3C) alkylene (C2-3) or oxiran-2,3-diyl; each of R3a, R3b, R3c, R3d, R3e, R3f and R3g is independently hydrogen or (1-4C) alkyl; R4 is a divalent group of formula: - (R4a) d- (A1) e- (R4b) fQ- (R4c) g- (A2) h- (R4d) ien which d, e, f, g, h and i are each independently selected from 0 and 1; R4a, R4b, R4c and R4d are each independently selected from alkylene (C1-10) alkenylene (2-10C) alkynylene (2-10C) alkynylene wherein each alkylene, alkenylene or is unsubstituted or substituted with 1 to 5 substituents independently selected from (1-4C) alkyl, fluoro, hydroxy, phenyl and phenyl (1-4C) alkyl; A1 and A2 are each independently selected from cycloalkylene (C3-7) arylene, (C6-10) -O-arylene (C6-10) arylene (C6-10) -O-, heteroarylene (C2-9), -O-heteroarylene (C2-9) heteroarilen (C2-9) heterocyclene -O- and (3-6C), wherein each cycloalkylene is unsubstituted or substituted with 1 to 4 substituents independently selected from (C1 4), and each arylene, heteroarylene or heterocyclene is unsubstituted or substituted with 1 to 4 substituents independently selected from halo, (1-4C) alkyl, (1-4C) alkoxy, -S (1-4C) , -S (O) (1-4C) alkyl, -S (O) 2 (C1-4) alkyl, -C (O) O (1-4C) alkyl, carboxy, cyano, hydroxy, nitro, trifluoromethyl and trifluoromethoxy; Q is selected from a bond, -O-, -C (O) O-, -OC (O) -, -S-, -S (O) -, -S (O) 2-, -N (Qa) C (O) -, -C (O) N (Qb) -, -N (Qc) S (O) 2-, -S (O) 2N (Qd) -, -N (Qc) C (O) N (Qf) -, -N (Qg) S (O) 2N (Qh) -, -OC (O) N (Qi) -, -N (Qj) C (O) O- and -N (Qk); Qa, Qb, Qc, Qd, Qe, Qf, Qg, Qh, Qi and Qj Qk are each independently selected from hydrogen, (1-6C) alkyl, A3 and alkylene (C1-4) -A4, wherein alkyl group is unsubstituted or substituted with 1 to 3 substituents independently selected from fluoro, hydroxy and (1-4C) alkoxy; or together with the nitrogen atom and R4b R4c or group to which they are attached form a azacycloalkylene group 4 to 6 members; A3 and A4 are each independently selected from (3-6C) cycloalkyl, (C6-10) aryl, heteroaryl (C2-9) and heterocyclyl (C3-6), wherein each cycloalkyl is unsubstituted or substituted with 1 to 4 substituents independently selected from (1-4C) alkyl and each hetorociclilo aryl, heteroaryl or is unsubstituted or substituted with 1 to 4 substituents independently selected from halo, (1-4C) alkyl and (1-4C) alkoxy; with the proviso that the number of contiguous atoms in the shortest chain between the two nitrogen atoms to which R4 is attached, is in the range of 4 to 16; R5 represents hydrogen or (1-4C) alkyl; R6 is -NR6aCR6b (O) or -CR6cR6dOR6c and R7 is hydrogen; or R6 and R7 together form -NR7aC (O) -CR7b> = CR7c-, -CR7d> = CR7c-C (O) -NR7f-, -NR7gC (O) -CR7hR7i-CR7jR7k- or - CR7lR7m-CR7nR7o- C ( O) -NR7p-; each of R6a, R6b, R6c, R6d and R6e is independently hydrogen or (1-4C) alkyl; and each of R7a, R7b, R7c, R7d, R7e, R7f, R 7g, R7h, R7i, R7j, R7k, R7l, R7M, R7N, R7O and R7p is independently hydrogen or (1-4C) alkyl; or a salt or solvate or stereoisomer thereof.