1-alkyl-1-azoniabicyclo' 2.2.2 octane carbamate derivatives and their use as muscarinic receptor antagonists

A compound of general formula (I)

• and individual isomers, racemic or non-racemic mixtures of isomers, and pharmaceutically acceptable salts thereof,
• wherein R1, R2 and R3 are radicals independently selected from the group consisting of H, OH, NO2, SH, CN, F, Cl, Br, I, COOH, CONH2, (C1-C4)-alkoxycarbonyl, (C1-C4-alkylsulfanyl, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkoxyl optionally substituted with one or several F, and (C1-C4)-alkyl optionally substituted with one or several F or OH;
• alternatively, either R1 and R2, or R2 and R3 may be forming a biradical selected from the group consisting of —CH2—CH2—CH2—, and —CH2—CH2—CH2—CH2—;
• R4 is a radical selected from the group consisting of:
• a) a C-linked radical of a five or six membered heterocyclic ring containing at least one heteroatom selected from the group consisting of O, S, and N, being this heterocyclic ring substituted with one or several substituents independently selected from the group consisting of OH, oxo (═O), SH, NO2, CN, F, Cl, Br, I, CONH2, COOH, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkyl optionally substituted with one or several F or OH, and (C1-C4)-alkoxyl optionally substituted with one or several F;
• b) a C-linked radical of a bicyclic ring system consisting of a phenyl ring fused to a five or six membered heterocyclic ring containing at least one heteroatom selected from the group consisting of O, S and N, being this bicyclic ring system optionally substituted with one or several substituents independently selected from the group consisting of OH, oxo (═O), SH, NO2, CN, F, Cl, Br, I, CONH2, COOH, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkyl optionally substituted with one or several F or OH, and (C1-C4)-alkoxyl optionally substituted with one or several F;
• and
• c) phenyl substituted with one or several substituents independently selected from the group consisting of OH, SH, NO2, CN, F, Cl, Br, I, CONH2, COOH, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkyl optionally substituted with one or several F or OH, and (C1-C4)-alkoxyl optionally substituted with one or several F;
• R5 is a radical selected from the group consisting of:
• a) cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, all of them optionally substituted with one or several substituents independently selected from the group consisting of OH, oxo (═O), SH, NO2, CN, F, Cl, Br, I, CONH2, NR7CO—(C1-C4)-alkyl, COOH, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkyl optionally substituted with one or several F or OH, and (C1-C4)-alkoxyl optionally substituted with one or several F;
• b) (C1-C10)-alkyl substituted with one or several radicals independently selected from the group consisting of R6, COR6, NH2, NR6R7, CONR6R7, NR7COR6, OH, OR6, COOR6, OCOR6, SO2R6, SH, SR6, SOR6, COSR6, SCOR6, CN, F, Cl, Br, NO2, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, norbornenyl, and bicyclo[2.2. 1] heptanyl;
• R6 is a radical selected from the group consisting of:
• a) (C1-C5)-alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, norbomenyl, bicyclo[2.2.1]heptanyl, all of them optionally substituted with one or several substituents independently selected from the group consisting of OH, oxo (═O), SH, NO2, CN, F, Cl, Br, I, CONH2, NR7CO—(C1-C4)-alkyl, COOH, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkyl optionally substituted with one or several F or OH, and (C1-C4)-alkoxyl optionally substituted with one or several F;
• b) phenyl optionally substituted with one or several substituents independently selected from the group consisting of OH, SH, NO2, CN, F, Cl, Br, I, CONH2, NR7CO—(C1-C4)-alkyl, COOH, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkyl optionally substituted with one or several F or OH, and (C1-C4)-alkoxyl optionally substituted with one or several F;
• c) a C-linked radical of a five or six membered heterocyclic ring containing at least one heteroatom selected from the group consisting of O, S, and N, being this heterocyclic ring optionally substituted with one or several substituents independently selected from the group consisting of OH, oxo (═O), SH, NO2, CN, F, Cl, Br, I, CONH2, NR7CO—(C1-C4)-alkyl, COOH, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkyl optionally substituted with one or several F or OH, and (C1-C4)-alkoxyl optionally substituted with one or several F;
• and
• d) a C-linked radical of a bicyclic ring system consisting of a phenyl ring fused to a five or six membered heterocyclic ring containing at least one heteroatom selected from the group consisting of O, S and N, being this bicyclic ring system optionally substituted with one or several substituents independently selected from the group consisting of OH, oxo (═O), SH, NO2, CN, F, Cl, Br, I, CONH2, COOH, NR7CO—(C1-C4)-alkyl, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkyl optionally substituted with one or several F or OH, and (C1-C4)-alkoxyl optionally substituted with one or several F;
• R7 is a radical selected from the group consisting of H, phenoxycarbonyl, benzyloxycarbonyl, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylcarbonyl, (C1-C4)-alkylsulfonyl, and (C1-C5)-alkyl;
• and
• X−is a physiologically acceptable anion.