Synthesis and structure-activity relationships of novel benzoxaboroles as a new class of antimalarial agents

  • Bioorg Med Chem Lett. 2011 Jan 15;21(2):644-51. doi: 10.1016/j.bmcl.2010.12.034.
Yong-Kang Zhang  1 ,  Jacob J Plattner ,  Yvonne R Freund ,  Eric E Easom ,  Yasheen Zhou ,  Jiri Gut ,  Philip J Rosenthal ,  David Waterson ,  Francisco-Javier Gamo ,  Inigo Angulo-Barturen ,  Min Ge ,  Zhiya Li ,  Lingchao Li ,  Yong Jian ,  Han Cui ,  Hailong Wang ,  Jian Yang
Affiliations
  • 1. Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA. [email protected]
PMID: 21195617 DOI: 10.1016/j.bmcl.2010.12.034
Abstract

A series of boron-containing benzoxaborole compounds was designed and synthesized for a structure-activity relationship investigation surrounding 7-(HOOCCH(2)CH(2))-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (1) with the goal of discovering a new antimalarial treatment. Compound 1 demonstrates the best potency (IC(50)=26nM) against Plasmodium falciparum and has good drug-like properties, with low molecular weight (206.00), low ClogP (0.86) and high water solubility (750μg/mL at pH 7).