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Identification of a 4-fluorobenzyl l-valinate amide benzoxaborole (AN11736) as a potential development candidate for the treatment of Animal African Trypanosomiasis (AAT).
Akama, Tsutomu; Zhang, Yong-Kang; Freund, Yvonne R; Berry, Pamela; Lee, Joanne; Easom, Eric E; Jacobs, Robert T; Plattner, Jacob J; Witty, Michael J; Peter, Rosemary; Rowan, Tim G; Gillingwater, Kirsten; Brun, Reto; Nare, Bakela; Mercer, Luke; Xu, Musheng; Wang, Jiangong; Liang, Hao.
Affiliation
  • Akama T; Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
  • Zhang YK; Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
  • Freund YR; Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
  • Berry P; Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
  • Lee J; Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
  • Easom EE; Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
  • Jacobs RT; Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
  • Plattner JJ; Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA.
  • Witty MJ; Global Alliance for Livestock and Veterinary Medicine, Doherty Building, Pentlands Science Park, Penicuik, Edinburgh EH26 0PZ, UK. Electronic address: michael.witty@galvmed.org.
  • Peter R; Global Alliance for Livestock and Veterinary Medicine, Doherty Building, Pentlands Science Park, Penicuik, Edinburgh EH26 0PZ, UK.
  • Rowan TG; Global Alliance for Livestock and Veterinary Medicine, Doherty Building, Pentlands Science Park, Penicuik, Edinburgh EH26 0PZ, UK.
  • Gillingwater K; Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
  • Brun R; Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
  • Nare B; Avista Pharma Solutions, 350 Tricenter Boulevard, Suite C, Durham, NC 27713, USA.
  • Mercer L; Avista Pharma Solutions, 350 Tricenter Boulevard, Suite C, Durham, NC 27713, USA.
  • Xu M; Wuxi AppTec (Tianjin) Co. Ltd., No. 168 NanHai Road, 10th Avenue, TEDA, Tianjin 300457, PR China.
  • Wang J; Wuxi AppTec (Tianjin) Co. Ltd., No. 168 NanHai Road, 10th Avenue, TEDA, Tianjin 300457, PR China.
  • Liang H; Wuxi AppTec (Tianjin) Co. Ltd., No. 168 NanHai Road, 10th Avenue, TEDA, Tianjin 300457, PR China.
Bioorg Med Chem Lett ; 28(1): 6-10, 2018 01 01.
Article in En | MEDLINE | ID: mdl-29169674
ABSTRACT
Novel l-valinate amide benzoxaboroles and analogues were designed and synthesized for a structure-activity-relationship (SAR) investigation to optimize the growth inhibitory activity against Trypanosoma congolense (T. congolense) and Trypanosoma vivax (T. vivax) parasites. The study identified 4-fluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-l-valinate (5, AN11736), which showed IC50 values of 0.15 nM against T. congolense and 1.3 nM against T. vivax, and demonstrated 100% efficacy with a single dose of 10 mg/kg against both T. congolense and T. vivax in mouse models of infection (IP dosing) and in the target animal, cattle, dosed intramuscularly. AN11736 has been advanced to early development studies.
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Full text: 1 Database: MEDLINE Main subject: Trypanosomiasis, African / Valine / Boron Compounds / Antiprotozoal Agents Type of study: Diagnostic_studies Limits: Animals Language: En Year: 2018 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Trypanosomiasis, African / Valine / Boron Compounds / Antiprotozoal Agents Type of study: Diagnostic_studies Limits: Animals Language: En Year: 2018 Type: Article