Quinuclidine derivatives and their use as muscarinic m3 receptor antagonists

A compound of formula I

• in salt or zwitterionic form wherein
• R1 and R2 are each independently phenyl, one or both of R1 and R2 being substituted at one, two or three positions by halo, C1-C8-alkyl or C1-C5-alkoxy, and R3 is hydrogen, hydroxy, C1-C8-alkyl, C1-C8-alkoxy or C1-C8-alkylthio;
• or R1 and R2 are each unsubstituted phenyl, and R3 is hydrogen, C1-C8-alkyl, C1-C8-alkoxy or C1-C8-alkylthio;
• or R1 is C3-C8-cycloalkyl or a 4- to 6-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur, R2 is phenyl optionally substituted at one, two or three positions by halo, C1-C3-alkyl or C1-C8-alkoxy, or R2 is a 4- to 6-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur, and R3 is hydrogen, hydroxy, C1-C8-alkyl, C1-C8-alkoxy or C1-C8-alkylthio;
• or —CR1R2R3 denotes 9H-fluoren-9-yl, 9,10,-dihydroanthracenyl-9-yl, 9-hydroxy-9,10-dihydroanthracenyl-9-yl, 9-hydroxy-9H-fluoren-9-yl, 9H-xanthen-9-yl, 9-hydroxy-9H-xanthen-9-yl, 5H-dibenzo[a,d]cyclohepten-5-yl or 5-hydroxy-5H-dibenzo[a,d]cyclohepten-5-yl;
• and R4 is C1-C8-alkyl substituted at one, two or three positions by —CO—N(R5)R6 where R5 is hydrogen or C1-C8-alkyl and R6 is a 4- to 6-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
• or R1 and R2 are each unsubstituted phenyl, R3 is hydroxy, and R4 is C1-C8-alkyl substituted at one, two or three positions by —CO—N(R5)R6 where R5 is hydrogen or C1-C4-alkyl and R6 is 5-methyl-3-isoxazolyl;
• or R1 and R2 are each unsubstituted phenyl, R3 is hydroxy, and R4 is 1-ethyl substituted at one, two or three positions by —CO—N(R5)R6 where R5 is hydrogen or C1-C4-alkyl and R6 is a 4- to 6-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
• with the proviso that the compound of formula I is not (R)-3-(2-Hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-(pyrazin-2-ylcarbamoyl-methyl)-1-azonia-bicyclo[2.2.2]octane, (R)-3-(2-Hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-(isoxazol-3-ylcarbamoylmethyl)-1-azonia-bicyclo[2.2.2]octane bromide or (R)-3-(2-Hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-(pyrimidin-4-ylcarbamoyl-methyl)-1-azonia-bicyclo[2.2.2]octane bromide.