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The discovery of potent antagonists of NPBWR1 (GPR7)
F Anthony Romero1, Nicholas B Hastings, Remond Moningka
1Merck & Co., Inc., Department of Medicinal Chemistry, PO Box 2000, Rahway, NJ 07065, USA. anthony_romero@merck.com
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).
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