1262279-06-0Relevant articles and documents
Optimization of isoxazoline amide benzoxaboroles for identification of a development candidate as an oral long acting animal ectoparasiticide
Zhang, Yong-Kang,Plattner, Jacob J.,Easom, Eric E.,Akama, Tsutomu,Zhou, Yasheen,White, W. Hunter,Defauw, Jean M.,Winkle, Joseph R.,Balko, Terry W.,Cao, Jianxin,Ge, Zhixin,Yang, Jianzhang
, p. 3182 - 3186 (2016/06/13)
Novel isoxazoline amide benzoxaboroles were designed and synthesized to optimize the ectoparasiticide activity of this chemistry series against ticks and fleas. The study identified an orally bioavailable molecule, (S)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)-2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamide (23), with a favorable pharmacodynamics profile in dogs (Cmax = 7.42 ng/mL; Tmax = 26.0 h; terminal half-life t1/2 = 127 h). Compound 23, a development candidate, demonstrated 100% therapeutic effectiveness within 24 h of treatment, with residual efficacy of 97% against American dog ticks (Dermacentor variabilis) on day 30 and 98% against cat fleas (Ctenocephalides felis) on day 32 after a single oral dose at 25 mg/kg in dogs.
Synthesis and biological evaluations of P4-benzoxaborole-substituted macrocyclic inhibitors of HCV NS3 protease
Ding, Charles Z.,Zhang, Yong-Kang,Li, Xianfeng,Liu, Yang,Zhang, Suoming,Zhou, Yasheen,Plattner, Jacob J.,Baker, Stephen J.,Liu, Liang,Duan, Maosheng,Jarvest, Richard L.,Ji, Jingjing,Kazmierski, Wieslaw M.,Tallant, Matthew D.,Wright, Lois L.,Smith, Gary K.,Crosby, Renae M.,Wang, Amy A.,Ni, Zhi-Jie,Zou, Wuxin,Wright, Jon
scheme or table, p. 7317 - 7322 (2011/01/12)
We disclose here a series of P4-benzoxaborole-substituted macrocyclic HCV protease inhibitors. These inhibitors are potent against HCV NS3 protease, their anti-HCV replicon potencies are largely impacted by substitutions on benzoxaborole ring system and P2 groups. P2 2-thiazole-isoquinoline provides best replicon potency. The in vitro SAR studies and in vivo PK evaluations of selected compounds are described herein.
