On March 15, 2015, Young, Wendy B.; Barbosa, James; Blomgren, Peter; Bremer, Meire C.; Crawford, James J.; Dambach, Donna; Gallion, Steve; Hymowitz, Sarah G.; Kropf, Jeffrey E.; Lee, Seung H.; Liu, Lichuan; Lubach, Joseph W.; Macaluso, Jen; Maciejewski, Pat; Maurer, Brigitte; Mitchell, Scott A.; Ortwine, Daniel F.; Di Paolo, Julie; Reif, Karin; Scheerens, Heleen; Schmitt, Aaron; Sowell, C. Gregory; Wang, Xiaojing; Wong, Harvey; Xiong, Jin-Ming; Xu, Jianjun; Zhao, Zhongdong; Currie, Kevin S. published an article.Recommanded Product: 87486-34-8 The title of the article was Potent and selective Bruton’s tyrosine kinase inhibitors: Discovery of GDC-0834. And the article contained the following:
SAR studies focused on improving the pharmacokinetic (PK) properties of the previously reported potent and selective Btk inhibitor CGI-1746 resulted in the clin. candidate GDC-0834, which retained the potency and selectivity of CGI-1746, but with much improved PK in preclin. animal models. Structure based design efforts drove this work as modifications to CGI-1746 were investigated at both the solvent exposed region as well as ‘H3 binding pocket’. However, in vitro metabolic evaluation of GDC-0834 revealed a non CYP-mediated metabolic process that was more prevalent in human than preclin. species (mouse, rat, dog, cyno), leading to a high-level of uncertainly in predicting human pharmacokinetics. Due to its promising potency, selectivity, and preclin. efficacy, a single dose IND was filed and GDC-0834 was taken in to a single dose phase I trial in healthy volunteers to quickly evaluate the human pharmacokinetics. In human, GDC-0834 was found to be highly labile at the exo-cyclic amide bond that links the tetrahydrobenzothiophene moiety to the central aniline ring, resulting in insufficient parent drug exposure. This information informed the back-up program and discovery of improved inhibitors. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Recommanded Product: 87486-34-8
The Article related to bruton tyrosine kinase inhibitor gdc0834 preparation structure activity pharmacokinetics, amide hydrolysis, bruton’s tyrosine kinase, btk, gdc-0834, kinase inhibitor, rheumatoid arthritis, single dose ind and other aspects.Recommanded Product: 87486-34-8