title: Synthesis and structure-activity relationships of novel benzoxaboroles as a new class of antimalarial agents.
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).
authors.affiliation: Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA. yzhang@anacor.com
authors.forename: Yong-Kang
authors.initials: YK
authors.lastname: Zhang
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Plattner
authors.forename: Yvonne R
authors.initials: YR
authors.lastname: Freund
authors.forename: Eric E
authors.initials: EE
authors.lastname: Easom
authors.forename: Yasheen
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: David
authors.initials: D
authors.lastname: Waterson
authors.forename: Francisco-Javier
authors.initials: FJ
authors.lastname: Gamo
authors.forename: Inigo
authors.initials: I
authors.lastname: Angulo-Barturen
authors.forename: Min
authors.initials: M
authors.lastname: Ge
authors.forename: Zhiya
authors.initials: Z
authors.lastname: Li
authors.forename: Lingchao
authors.initials: L
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Jian
authors.forename: Han
authors.initials: H
authors.lastname: Cui
authors.forename: Hailong
authors.initials: H
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D001896:Boron Compounds