Development of Quinazoline/Pyrimidine-2,4(1 H,3 H)-diones as Agonists of Cannabinoid Receptor Type 2

Hai-Yan Qian; Zhi-Long Wang; You-Lu Pan; Li-Li Chen; Xin Xie; Jian-Zhong Chen

doi:10.1021/acsmedchemlett.7b00007

Development of Quinazoline/Pyrimidine-2,4(1 H,3 H)-diones as Agonists of Cannabinoid Receptor Type 2

ACS Med Chem Lett. 2017 May 1;8(6):678-681. doi: 10.1021/acsmedchemlett.7b00007. eCollection 2017 Jun 8.

Authors

Hai-Yan Qian¹, Zhi-Long Wang², You-Lu Pan¹, Li-Li Chen¹, Xin Xie², Jian-Zhong Chen¹

Affiliations

¹ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. China.
² CAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China.

Abstract

Starting from a prototypical structure 1, we describe our efforts to design and obtain novel quinazoline/pyrimidine-2,4(1H,3H)-diones with high CB2 agonist potency and selectivity as well as improved physicochemical characteristics, mainly hydrophilicity. The most potent and selective CB2 agonists, 8 and 36, in this series were also endowed with lower logP values than that of GW842166X and lead compound 1. These derivatives appear to be promising lead compounds for the development of future CB2 agonists.

Keywords: CB2 agonist; Cannabinoid receptors; molecular modeling; structure−activity relationship.