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Synthesis of Hexahydro‐2‐pyrindine (=Hexahydrocyclopenta[ c ]pyridine) Derivatives as Conformationally Restricted Analogs of the Nicotinic Ligands Arecolone and Isoarecolone
Author(s) -
Guandalini Luca,
Dei Silvia,
Gualtieri Fulvio,
Romanelli Maria Novella,
Scapecchi Serena,
Teodori Elisabetta,
Varani Katia
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200201)85:1<96::aid-hlca96>3.0.co;2-7
Subject(s) - chemistry , nicotinic agonist , methiodide , pyridine , stereochemistry , acetylcholine receptor , receptor , medicinal chemistry , biochemistry
Two hexahydropyrindine derivatives, 1,2,3,4,6,7‐hexahydro‐2‐methyl‐5 H ‐cyclopenta[ c ]pyridin‐5‐one ( 1 ) and 1,2,3,4,5,6‐hexahydro‐2‐methyl‐7 H ‐cyclopenta[ c ]pyridin‐7‐one ( 2 ), and their methiodides 14 and 26 , respectively, were synthesized. They can be considered rigid analogues of the known nicotinic agonists arecolone (=1‐(1,2,5,6‐tetrahydro‐1‐methylpyridin‐3‐yl)ethanone) and isoarecolone (=1‐(1,2,3,6‐tetrahydro‐1‐methylpyridin‐4‐yl)ethanone). The affinity for the central nicotinic receptor were measured on rat cerebral cortex. Although only the methiodide 14 , among the four conformationally restricted compounds, shows an appreciable affinity, the results obtained provide useful information on the molecular requirements at the interaction site of the central nicotinic receptors.