| 摘要 |
Hexahydro-chromeno[3,4-c]pyrrole-8-carbonitrile compounds (I) and their positional isomers, enantiomers, diastereoisomers, and addition salts with an acid or a base are new. Hexahydro-chromeno[3,4-c]pyrrole-8-carbonitrile compounds of formula (I) and their positional isomers, enantiomers, diastereoisomers, and addition salts with an acid or a base are new. R 1>R 2> : group of formula (-(CH 2) 2-N(R 3>)(R 4>)-(CH 2) 2-); R 3> : H or 1-6C alkyl, preferably H or CH 3; R 4> : 1-6C alkyl, aryl, heteroaryl or 3,4-dioxocyclobutenyl (all optionally substituted by one or more halo), amino or aminocarbonyl (both optionally substituted by one or more 1-6C alkyl), 1-6C alkylcarbonyl, 1-6C alkyl, carboxy, OH, CN, nitro, H, -COR 5>, or -SO 2R 5>; NR 3>R 4> : 5-8 membered ring optionally substituted by one or more halo, linear or branched 1-6C alkyl, hydroxy, oxo or amino (optionally substituted by 1-6C alkyl); and R 5> : 1-6C alkyl, 3-8C cycloalkyl, heterocycloalkyl, aryl or heteroaryl (all optionally substituted by one or more halo), 1-6C alkylcarbonyl, 1-6C alkyl, carboxy, hydroxy, cyano, nitro, amino or aminocarbonyl (both optionally substituted by one or more 1-6C alkyl). An independent claim is included for the preparation of (I). [Image] - ACTIVITY : Neuroleptic; Antiaddictive; Tranquilizer; Antidepressant; Antiparkinsonian; Inotropic; Nootropic; Analgesic; Antiemetic; Antiinfertility; Nephrotropic. - MECHANISM OF ACTION : Dopamine 3 (D3) receptor modulator; Dopamine 2 receptor modulator. The ability of (I) to bind dopamine 3 receptor was tested in Chinese hamster ovary cells. The result showed that N-(trans-4-{2-[(3aS,9bR)- 8-cyano-1,3a,4,9b-tetrahydrochromeno[3,4-c]pyrrol-2(3H)-yl]ethy l}cycl ohexyl)acetamide hydrochloride exhibited the negative logarithm of dissociation constant (pK i) of 8.70+- 0.05.
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