The discovery of potent antagonists of NPBWR1 (GPR7).

Bioorganic & medicinal chemistry letters (2011-12-27)
F Anthony Romero, Nicholas B Hastings, Remond Moningka, Zhiqiang Guo, Ming Wang, Jerry Di Salvo, Ying Lei, Dorina Trusca, Qiaolin Deng, Vincent Tong, Jenna L Terebetski, Richard G Ball, Feroze Ujjainwalla
ABSTRACT

The synthesis and evaluation of small molecule antagonists of the G protein-coupled receptor NPBWR1 (GPR7) are reported for the first time. [4-(5-Chloropyridin-2-yl)piperazin-1-yl][(1S,2S,4R)-4-{[(1R)-1-(4-methoxyphenyl)ethyl]amino}-2-(thiophen-3-yl)cyclohexyl]methanone (1) emerged as a hit from a high-throughput screen. Examination of substituents that focused on replacing the 5-chloropyridine and 4-methoxybenzylamino groups of 1 led to the identification of compounds that exhibited subnanomolar potencies as low as 660pM (9k) in the functional assay and 200pM in the binding assay (9i).

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Benzylamine, ReagentPlus®, 99%
Sigma-Aldrich
Benzylamine hydrochloride
Supelco
Benzylamine, for GC derivatization, LiChropur, ≥99.0%
Sigma-Aldrich
Benzylamine, purified by redistillation, ≥99.5%