Author: Tsutomu Akama, Yong-Kang Zhang, Yvonne R. Freund, Pamela Berry, Joanne Lee, Eric E. Easom, Robert T. Jacobs, Jacob J. Plattner, Michael J. Witty, Rosemary Peter, Tim G. Rowan, Kirsten Gillingwater, Reto Brun, Bakela Nare, Luke Mercer, Musheng Xu, Jiangong Wang, Hao Liang
Year: 2017
About this Publication:
Novel L-valinate amide benzoxaboroles and analogues were designed and synthesized for a structureactivity-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.
Grant: Tryps2
Subject Areas: Research and Development
Diseases: Trypanosomosis
Keywords:
AAT, African African Trypanosomosis, Benzoxaborole, Cattle, Lead optimisation, Protozoan, R&D, SAR, Trypanosomiasis, Trypanosomosis, Tryps, potential candidate
Countries:
Benin, Botswana, Burkina Faso, Burundi, Cape Verde, Comoros, Cote D'Ivoire, Djibouti, Eritrea, Ethiopia, Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mayotte, Mozambique, Namibia, Niger, Nigeria, Reunion, Rwanda, Saint Helena, Senegal, Seychelles, Sierra Leone, Somalia, South Africa, Swaziland, Tanzania, United Republic Of, Togo, Uganda, Zambia, Zimbabwe