Synthesis of Hexahydro-2-pyrindine (=Hexahydrocyclopenta[c]pyridine) Derivatives as Conformationally Restricted Analogs of the Nicotinic Ligands Arecolone and Isoarecolone

Abstract

Two hexahydropyrindine derivatives, 1,2,3,4,6,7-hexahydro-2-methyl-5H-cyclopenta[c]pyridin-5-one (1) and 1,2,3,4,5,6-hexahydro-2-methyl-7H-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.

Dearomative (3+2) Cycloadditions between Indoles and Vinyldiazo Species Enabled by a Red‐Shifted Chromium Photocatalyst

“…Cross couplings with the aryl bromide moiety can be achieved with aryl or heteroaryl boron reagents ( 15 a , b ). Allylic oxidation affords enone 16 , [35] while DIBAL reduction generates hemiaminal ether 17 [36] . The fused 5,5‐ring system allows for diastereoselective transformations.…”

Nicotinic Agonists, Antagonists, and Modulators From Natural Sources

“…Other carbamates have been reported Saraswati et al, 1994). A cyclic analog I had quite low affinity for α 4 β 2 receptors (Guandalini et al, 2002). Another analog AG-4 also had low affinity .…”

New Trends in the Design of Drugs Against Alzheimer's Disease

“…Recently, the affinity of novel rigid analogs of arecoline (11) and isoarecoline (12) such as (13) for central nAChRs was evaluated in vitro, providing information on the molecular requirements for developing new active compounds [15]. On the other hand, new 3-substituted quinuclidines (14) were patented as nicotinic agonists [16].…”