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Papers of the Week

Papers: 2 Mar 2019 - 8 Mar 2019

Animal Studies, Pharmacology/Drug Development

2019 May 01

Bioorg Med Chem Lett



Discovery of NR2B-selective antagonists via scaffold hopping and pharmacokinetic profile optimization.


Anan K, Masui M, Tazawa A, Tomida M, Haga Y, Kume M, Yamamoto S, Shinohara S, Tsuji H, Shimada S, Yagi S, Hasebe N, Kai H
Bioorg Med Chem Lett. 2019 May 01; 29(9):1143-1147.
PMID: 30833109.


Selective N-methyl-d-aspartate receptor subunit 2B (NR2B) antagonists show potential as analgesic drugs, and do not cause side effects associated with non-selective N-methyl-d-aspartate (NMDA) antagonists. Using a scaffold-hopping approach, we previously identified isoxazole derivative 4 as a potent selective NR2B antagonist. In this study, further scaffold hopping of isoxazole derivative 4 and optimization of its pharmacokinetic profile led to the discovery of the orally bioavailable compound 6v. In a rat study of analgesia, 6v demonstrated analgesic effects against neuropathic pain.