Discovery of an orally bioavailable isoxazoline benzoxaborole (AN8030) as a long acting animal ectoparasiticide.
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.
Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
Yong-Kang
YK
Zhang
Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
Jacob J
JJ
Plattner
Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
Eric E
EE
Easom
Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
Yasheen
Y
Zhou
Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
Tsutomu
T
Akama
Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
Wei
W
Bu
Elanco Animal Health Research and Development, A Division of Eli Lilly & Company, 2500 Innovation Way, Greenfield, IN 46140, USA.
W Hunter
WH
White
Elanco Animal Health Research and Development, A Division of Eli Lilly & Company, 2500 Innovation Way, Greenfield, IN 46140, USA.
Jean M
JM
Defauw
Elanco Animal Health Research and Development, A Division of Eli Lilly & Company, 2500 Innovation Way, Greenfield, IN 46140, USA.
Joseph R
JR
Winkle
Elanco Animal Health Research and Development, A Division of Eli Lilly & Company, 2500 Innovation Way, Greenfield, IN 46140, USA.
Terry W
TW
Balko
Shanghai Medicilon, Inc., 585 Chuanda Road, Zhangjiang High-tech Park, Pudong New Area, Shanghai 201200, China.
Shenghai
S
Guo
Shanghai Medicilon, Inc., 585 Chuanda Road, Zhangjiang High-tech Park, Pudong New Area, Shanghai 201200, China.
Jian
J
Xue
Shanghai ChemPartner, 998 Halei Road, Zhangjiang High-tech Park, Pudong New Area, Shanghai 201203, China.
Jianxin
J
Cao
BioDuro LLC, Building E, No. 29, Life Science Park Road, Beijing 102206, China.
Wuxin
W
Zou
D000284:Administration, Oral; D000818:Animals; D001896:Boron Compounds / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D004283:Dog Diseases / Q000188:drug therapy* / Q000469:parasitology; D004285:Dogs; D055808:Drug Discovery; D004478:Ectoparasitic Infestations / Q000188:drug therapy*; D007555:Isoxazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013997:Time Factors
C000611191:AN8030; D001896:Boron Compounds; D007555:Isoxazoles
Benzoxaborole; Ectoparasiticide; Isoxazoline; Structure–activity relationship; Tick and flea