Agonists for the adenosine A1 receptor with tunable residence time. A case for nonribose 4-amino-6-aryl-5-cyano-2-thiopyrimidines

…, L Xia, H de Vries, J Brussee, LH Heitman…

Index: Louvel, Julien; Guo, Dong; Agliardi, Marta; Mocking, Tamara A. M.; Kars, Roland; Pham, Tan Phat; Xia, Lizi; De Vries, Henk; Brussee, Johannes; Heitman, Laura H.; Ijzerman, Adriaan P. Journal of Medicinal Chemistry, 2014 , vol. 57, # 8 p. 3213 - 3222

Full Text: HTML

Citation Number: 18

Abstract

We report the synthesis and evaluation of previously unreported 4-amino-6-aryl-5-cyano-2- thiopyrimidines as selective human adenosine A1 receptor (hA1AR) agonists with tunable binding kinetics, this without affecting their nanomolar affinity for the target receptor. They show a very diverse range of kinetic profiles (from 1 min (compound 52) to 1 h (compound 43)), and their structure–affinity relationships (SAR) and structure–kinetics relationships ( ...