Doherty, Elizabeth M.; Fotsch, Christopher; Bannon, Anthony W.; Bo, Yunxin; Chen, Ning; Dominguez, Celia; Falsey, James; Gavva, Narender R.; Katon, Jodie; Nixey, Thomas; Ognyanov, Vassil I.; Pettus, Liping; Rzasa, Robert M.; Stec, Markian; Surapaneni, Sekhar; Tamir, Rami; Zhu, Jiawang; Treanor, James J. S.; Norman, Mark H. published an article in Journal of Medicinal Chemistry. The title of the article was 《Novel Vanilloid Receptor-1 Antagonists: 2. Structure-Activity Relationships of 4-Oxopyrimidines Leading to the Selection of a Clinical Candidate》.Related Products of 659729-09-6 The author mentioned the following in the article:
A series of novel 4-oxopyrimidine TRPV1 antagonists was evaluated in assays measuring the blockade of capsaicin or acid-induced influx of calcium into CHO cells expressing TRPV1. The investigation of the structure-activity relationships in the heterocyclic A-region revealed the optimum pharmacophoric elements required for activity in this series and resulted in the identification of subnanomolar TRPV1 antagonists. The most potent of these antagonists were thoroughly profiled in pharmacokinetic assays. Optimization of the heterocyclic A-region led to the design and synthesis of 23 (I), a compound that potently blocked multiple modes of TRPV1 activation. Compound 23 was shown to be effective in a rodent “”on-target”” biochem. challenge model (capsaicin-induced flinch, ED50 = 0.33 mg/kg p.o.) and was antihyperalgesic in a model of inflammatory pain (CFA-induced thermal hyperalgesia, MED = 0.83 mg/kg, p.o.). Based on its in vivo efficacy and pharmacokinetic profile, compound 23 (N-{4-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl}-acetamide; AMG 517) was selected for further evaluation in human clin. trials. The experimental part of the paper was very detailed, including the reaction process of 4-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine(cas: 659729-09-6Related Products of 659729-09-6)
4-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine(cas: 659729-09-6) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Related Products of 659729-09-6
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia