219635-87-7Relevant academic research and scientific papers
Synthesis and evaluation of pyridazinylpiperazines as vanilloid receptor 1 antagonists
Tafesse, Laykea,Sun, Qun,Schmid, Lori,Valenzano, Kenneth J.,Rotshteyn, Yakov,Su, Xin,Kyle, Donald J.
, p. 5513 - 5519 (2004)
A series of pyridazinylpiperazines were synthesized and evaluated for VR1 antagonist activity in order to improve upon the pharmaceutical and pharmacological properties of BCTC. A structurally biased chemical library of pyridazinylpiperazine analogs was prepared in an effort to improve the pharmaceutical and pharmacological profile of the lead compound N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H) -carboxamide (BCTC). The library was evaluated for VR1 antagonist activity in capsaicin-induced (CAP) and pH 5.5-induced (pH) FLIPR assays in a human VR1-expressing HEK293 cell line. The most potent VR1 antagonists were found to have IC50 values in the range of 9-200 nM with improved pharmaceutical and pharmacological profiles versus the lead BCTC. These compounds represent possible second-generation BCTC analogs.
