Pyrrole Derivatives as Alpha 7 nAChR Modulators

摘要

Disclosed are compounds of the formula (I), wherein R1, R2, R3, R4, R5, R6, R7 and m are as described herein, as modulators of the nicotinic acetylcholine receptors, particularly the α7 subtype, their tautomeric forms, stereoisomers, and their pharmaceutically acceptable salts, pharmaceutical compositions thereof, and combinations thereof with suitable other medicaments. Also disclosed are a process of preparation of the compounds and the intended uses thereof in therapy, particularly in the prophylaxis and/or treatment of disorders such as Alzheimer's disease, mild cognitive impairment, and senile dementia.;

主权项

1. A compound of formula (I), a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein, R1 is selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl; R2 is selected from substituted- or unsubstituted-alkyl and substituted- or unsubstituted-cycloalkyl; R3 is selected from the group consisting of substituted- or unsubstituted-aryl and substituted- or unsubstituted-heteroaryl; R4 is selected from the group consisting of substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-heterocyclyl, and —NR8R9; R5 is selected independently at each occurrence from the group consisting of halogen, substituted- or unsubstituted-alkyl, perhaloalkyl, substituted- or unsubstituted-cycloalkyl, —OR8b, —NR8R9, and —C(═O)R8a; or R6 and R7 are independently selected from the group consisting of hydrogen and substituted- or unsubstituted-alkyl; R8 and R9 are each independently selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl; R8a is selected from the group consisting of substituted- or unsubstituted-alkyl, perhaloalkyl, and substituted- or unsubstituted-cycloalkyl; R8b is selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, perhaloalkyl, and substituted- or unsubstituted-cycloalkyl; m is an integer selected from 0, 1, and 2; when the alkyl group is substituted, it is substituted with 1 to 3 substituents independently selected from oxo, halogen, nitro, cyano, perhaloalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, —OR10b, —SO2R10a, —C(═O)OR10a, —OC(═O)R10a, —C(═O)N(H)R10, —C(═O)N(alkyl)R10, —N(H)C(═O)R10a, —N(H)R10, —N(alkyl)R10, —N(H)C(═O)N(H)R10, and —N(H)C(═O)N(alkyl)R10; when the cycloalkyl group is substituted, it is substituted with 1 to 3 substituents independently selected from oxo, halogen, nitro, cyano, alkyl, perhaloalkyl, aryl, heteroaryl, heterocyclyl, —OR10b, —SO2R10c, —C(═O)R10c, —C(═O)OR10c, —OC(═O)R10c, —C(═O)N(H)R10d, —C(═O)N(alkyl)R10d, —N(H)C(═O)R10c, —N(H)R10d, —N(alkyl)R10d, —N(H)C(═O)N(H)R10d, and —N(H)C(═O)N(alkyl)R10d; when the aryl group is substituted, it is substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, hydroxy, alkyl, perhaloalkyl, cycloalkyl, heterocyclyl, —O-alkyl, —O-perhaloalkyl, —N(alkyl)alkyl, —N(H)alkyl, —NH2, —SO2-alkyl, —SO2-perhaloalkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)alkyl, —C(═O)N(alkyl)alkyl, —C(═O)N(H)alkyl, —C(═O)NH2, —SO2N(alkyl)alkyl, —SO2N(H)alkyl, and —SO2NH2; when the heteroaryl group is substituted, it is substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, hydroxy, alkyl, perhaloalkyl, cycloalkyl, heterocyclyl, —O-alkyl, —O-perhaloalkyl, —N(alkyl)alkyl, —N(H)alkyl, —NH2, —SO2-alkyl, —SO2-perhaloalkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)alkyl, —C(═O)N(alkyl)alkyl, —C(═O)N(H)alkyl, —C(═O)NH2, —SO2N(alkyl)alkyl, —SO2N(H)alkyl, and —SO2NH2; when the heterocyclyl group is substituted, it can be substituted either on a ring carbon atom(s) or on a ring hetero atom; when it substituted on a ring carbon atom(s), it is substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, oxo, alkyl, perhaloalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, —OR10b, —C(═O)OR10c, —OC(═O)R10c, —C(═O)N(H)R10d, —C(═O)N(alkyl)R10d, —N(H)C(═O)R10c, —N(H)R10d, —N(alkyl)R10d, —N(H)C(═O)N(H)R10d, and —N(H)C(═O)N(alkyl)R10d; and when the heterocyclyl group is substituted on a ring nitrogen, it is substituted with a substituent selected from alkyl, cycloalkyl, aryl, heteroaryl, —SO2R10c, —C(═O)R10c, —C(═O)N(H)R10d, and —C(═O)N(alkyl)R10d; R10 is selected from hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl; R10a is selected from alkyl, perhaloalkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl; R10b is selected from hydrogen, alkyl, perhaloalkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl; R10c is selected from alkyl, perhaloalkyl, and cycloalkyl; R10d is selected from hydrogen, alkyl, and cycloalkyl.