177167-50-9Relevant academic research and scientific papers
Fragment-based lead discovery of a novel class of small molecule antagonists of neuropeptide B/W receptor subtype 1 (GPR7)
Moningka, Remond,Romero, F. Anthony,Hastings, Nicholas B.,Guo, Zhiqiang,Wang, Ming,Di Salvo, Jerry,Li, Ying,Trusca, Dorina,Deng, Qiaoling,Tong, Vincent,Terebetski, Jenna L.,Ball, Richard G.,Ujjainwalla, Feroze
, (2020)
Here, we report the discovery of a new class of NPBWR1 antagonists identified from a fragment-based screen. Compound 1 (cAMP IC50 = 250 μM; LE = 0.29) emerged as an initial hit. Further optimization of 1 by SAR-by-catalogue and chemical modification produced 21a (cAMP IC50 = 30 nM; LE = 0.39) with a 6700-fold increase in potency from fragment 1. Somewhat surprisingly, Schild analysis of compound 21a suggested that in vitro inhibition of NPW-mediated effects on upon cAMP accumulation were saturable, and that compound 21a dose-dependently increased [125I]-hNPW23 dissociation rate constants from NPBWR1 in kinetic binding studies. Collectively, these data are inconsistent with a classic surmountable, orthosteric mechanism of inhibition. The benzimidazole inhibitors reported herein may therefore represent a mechanistically differentiated class of compounds with which to form a better appreciation of the pharmacology and physiological roles of this central neuropeptide system.
Synthesis of regiospecifically meso-functionalized tetraarylporphyrins via arylbis(2-pyrrolyl)methanes
Banfi, Stefano,Manfredi, Amedea,Pozz, Gianluca,Quici, Silvio,Trebicka, Artan
, p. 179 - 185 (2007/10/03)
This paper describes the synthesis of three new porphyrins 1-3 of alternate A2B2 structure, by condensation of arylbis(2-pyrrolyl)methanes and arylaldehydes bearing suitable reactive substituents for further synthetic manipulations. This synthetic approach allows to place the reactive groups selectively on the 5,15 meso-aryls. The new porphyrins feature an ortho-nitro group in the case of 1 and a protected paraethynyl group in compounds 2 and 3. Porphyrin l, after reduction of the nitro group, is a useful intermediate for the preparation of cage or regiospecifically bis-tailed porphyrins. Compounds 2 and 3, after deprotection and Glaser-Hay coupling should give linear polymers (molecular wires) suitable for electron-transfer and light-harvesting processes.
