- Optimization of isoxazoline amide benzoxaboroles for identification of a development candidate as an oral long acting animal ectoparasiticide
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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.
- 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
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p. 3182 - 3186
(2016/06/13)
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- BORON-CONTAINING SMALL MOLECULES
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This invention provides novel compounds, methods of using the compounds, and pharmaceutical compositions containing the compounds.
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