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

Bioorg Med Chem Lett. 2015 Dec 1;25(23):5589-93. doi: 10.1016/j.bmcl.2015.10.044. Epub 2015 Oct 23.

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(3H)-ol (38, AN8030), which was long lasting in dogs (t1/2=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.

Keywords: Benzoxaborole; Ectoparasiticide; Isoxazoline; Structure–activity relationship; Tick and flea.

MeSH terms

  • Administration, Oral
  • Animals
  • Boron Compounds / administration & dosage
  • Boron Compounds / chemistry*
  • Boron Compounds / pharmacology
  • Dog Diseases / drug therapy*
  • Dog Diseases / parasitology
  • Dogs
  • Drug Discovery*
  • Ectoparasitic Infestations / drug therapy*
  • Isoxazoles / administration & dosage
  • Isoxazoles / chemical synthesis*
  • Isoxazoles / chemistry
  • Isoxazoles / pharmacology
  • Molecular Structure
  • Structure-Activity Relationship
  • Time Factors

Substances

  • AN8030
  • Boron Compounds
  • Isoxazoles