162933-93-9Relevant academic research and scientific papers
Synthesis of Perhydro-1,4-ethano-1,5-naphthyridine and Perhydro-4,7-ethanopyrrolopyridine Derivatives: Potential NK1-receptor Antagonists. X-Ray Molecular Structures of (4aR*,8S*,8aR*)-6-Oxo-8-phenylperhydro-1,4-ethano-1,5-naphthyridine and (4aR*,7R*,8R*,8aR*)-7,8-Diphenylper...
Besidsky, Yevgeny,Luthman, Kristina,Claesson, Alf,Fowler, Christopher J.,Csoeregh, Ingeborg,Hacksell, Uli
, p. 465 - 474 (2007/10/02)
Derivatives of perhydro-1,4-ethano-1,5-naphthyridine and 4,7-ethanopyrrolopyridine were designed and synthesized as conformationally constrained analogues of the potent NK1-receptor antagonist CP-96,345. 2-Benzylidenequinuclidin-3-one 1 was used as the common starting material: (i) heterocyclizations of compound 1 with N-(carbamoylmethyl)pyridinium chloride gave unsaturated pyridone derivatives which, after catalytic hydrogenation, afforded 1,5-naphthyridines, and (ii) functionalization of compound 1 by nucleophilic 1,4-addition reactions, followed by reductive cyclizations, gave quinuclidine derivatives with fused five- or six-membered rings.The cyclization reactions proceeded stereoselectively and the relative stereochemistries were determined by a combination of molecular mechanics calculations, X-ray crystallography, and NMR spectroscopy.The biological activities of the synthesized derivatives were evaluated by binding studies to human NK1-receptors in UC11MG cells.The compounds had low to moderate affinity for the NK1-receptor.
