New enantiomerically pure hexahydro-pyrrolo-cyclopenta-pyridine derivatives, useful as central nicotine receptor subtype agonists for e.g. treating Alzheimer's or Parkinson's disease, anxiety and depresssion

摘要

Enantiomerically pure (3aalpha ,8balpha )-1,2,3,3a,4,8b-hexahydro-pyrrolo-(2',3':3,4)-cyclopenta-(1,2-b)-pyridine or -(3',2':4,5)-cyclopenta-(1,2-c)-pyridine derivatives (I) are new. Enantiomerically pure (3aalpha ,8balpha )-1,2,3,3a,4,8b-hexahydro-pyrrolo-(2',3':3,4)-cyclopenta-(1,2-b)-pyridine or -(3',2':4,5)-cyclopenta-(1,2-c)-pyridine derivatives of formula (I) and their salts, are new. Z : direct bond or CH 2; R 1H or optionally unsaturated and/or perfluorinated 1-4C alkyl; R 2, R 3R 1, 1-4C alkoxy, 1-4C alkylthio or halo; X, Y : CH or N; and provided that when one of X, Y is CH, then the other is N. An independent claim is also included for the preparation of (I). [Image] ACTIVITY : Nootropic; Neuroprotective; Antiparkinsonian; Neuroleptic; Tranquilizer; Antidepressant; Anorectic; Analgesic; Antismoking. MECHANISM OF ACTION : Central nicotine receptor subtype agonist. In an assay for binding of ( 3>H)-cytisine to the alpha 4beta 2 subtype receptor in rat cerebral membranes, (-)-(3aR-(3aalpha ,8balpha ))-1,2,3,3a,4,8b-hexahydro-pyrrolo-(3',2':4,5)-cyclopenta-(1,2-c)-pyridine dihydrochloride (Ia) had K i 15.2 nM, compared with 1110 nM for the corresponding (+)-(3aS enantiomer.