2. Academic Validation
  3. Stereoselective synthesis of a novel 2-aza-7-oxabicyclo[3.3.0]octane as neurokinin-1 receptor antagonist

Stereoselective synthesis of a novel 2-aza-7-oxabicyclo[3.3.0]octane as neurokinin-1 receptor antagonist

  • Bioorg Med Chem Lett. 2007 Dec 15;17(24):6887-90. doi: 10.1016/j.bmcl.2007.10.010.
Yuji Shishido 1,  Fumitaka Ito,  Hiromasa Morita,  Masaya Ikunaka
Affiliations

Affiliation

  • 1 Pfizer Global Research & Development, Nagoya Laboratories, 5-2 Taketoyo, Aichi 470-2394, Japan.
PMID: 17967540 DOI: 10.1016/j.bmcl.2007.10.010
Abstract

A novel neurokinin-1 receptor antagonist, (+/-)-(1R( *),3S( *),4S( *),5S( *))-4-[(N-(2-methoxy-5-trifluoromethoxybenzyl)amino]-3-phenyl-2-aza-7-oxabicyclo[3.3.0]octane (1), was synthesized stereoselectively using Padwa's intramolecular 1,3-dipolar cycloaddition methodology as the key step. Compound (+/-)-1 showed high affinity for the NK-1 receptors in human IM-9 cells with an IC(50) value of 0.22 nM. This new structural scaffold demonstrated significant in vivo antagonistic activity in the guinea pig ureter capsaicin-induced plasma extravasation model with an ED(50) value of 1-10mg/kg, po.

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