Optimization of isoxazoline amide benzoxaboroles for identification of a development candidate as an oral long acting animal ectoparasiticide.
Bioorg Med Chem Lett
; 26(13): 3182-3186, 2016 07 01.
Article
in En
| MEDLINE
| ID: mdl-27210432
ABSTRACT
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=7.42ng/mL; Tmax=26.0h; terminal half-life t1/2=127h). Compound 23, a development candidate, demonstrated 100% therapeutic effectiveness within 24h 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 25mg/kg in dogs.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Boron Compounds
/
Dermacentor
/
Ectoparasitic Infestations
/
Ctenocephalides
/
Amides
/
Isoxazoles
/
Antiparasitic Agents
Type of study:
Diagnostic_studies
Limits:
Animals
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2016
Type:
Article
Affiliation country:
United States