Referenced in: none

Automatically associated channels: Kir2.3

Title: Synthesis and nicotinic binding studies on enantiopure pinnamine variants with an 8-azabicyclo[3.2.1]octane moiety.

Authors: S Schwarz, T Kämpchen, M C Tilotta, D Gündisch, G Seitz

Journal, date & volume: Pharmazie, 2003 May , 58, 295-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12779043

Abstract
Bioisosteric replacement of the 9-azabicyclo[4.2.1]nonane pharmacophoric element of the novel alkaloidal marine toxine pinnamine (5) by the 8-azabicyclo[3.2.1]octane moiety resulted in conformationally restricted analogues 6a and 6c of (-)-ferruginine (4). Key step in the diastereoselective synthesis of these pyranotropanes was the condensation of enantiopure ecgonine methyl ester (9) from the "chiral pool" with the lithium anion of N-tert-butylbutyraldimin and subsequent cyclisation with TFA. The potential nAChR ligands were tested for their in vitro affinity for the (alpha4)2(beta2)3 and the alpha7* nAChR subtypes. Despite obvious structural similarities with the potent alkaloids pinnamine (5) and (-)-ferruginine (4) the pyranotropanes 6a and 6c exhibited distinctly lower nAChR affinities.