Discovery of an orally bioavailable isoxazoline benzoxaborole (AN8030) as a long acting animal ectoparasiticide

Abstract A novel series of isoxazoline benzoxaborole small molecules was designed and synthesized for a structure–activity relationship (SAR) investigation to assess the ectoparasiticide activity against ticks and fleas. The study identified an orally bioavailable molecule, ( S )-3,3-dimethyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[ c ][1,2]oxaborol-1(3 H )-ol ( 38 , AN8030 ), which was long lasting in dogs ( t 1/2  = 22 days). Compound 38 demonstrated 97.6% therapeutic effectiveness within 24 h of treatment, with residual efficacy of 95.3% against American dog ticks ( Dermacentor variabilis ) on day 30% and 100% against cat fleas ( Ctenocephalides felis ) on day 32 after a single oral dose at 50 mg/kg in dogs.