title: Benzoxaborole antimalarial agents. Part 2: Discovery of fluoro-substituted 7-(2-carboxyethyl)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles.
abstract: A series of new boron-containing benzoxaborole compounds was designed and synthesized for a continuing structure-activity relationship (SAR) investigation to assess the antimalarial activity changes derived from side-chain structural variation, substituent modification on the benzene ring and removal of boron from five-membered oxaborole ring. This SAR study demonstrated that boron is required for the antimalarial activity, and discovered that three fluoro-substituted 7-(2-carboxyethyl)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles (9, 14 and 20) have excellent potencies (IC(50) 0.026-0.209 μM) against Plasmodium falciparum.
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: Long
authors.initials: L
authors.lastname: Ye
authors.forename: Huchen
authors.initials: H
authors.lastname: Zhou
authors.forename: David
authors.initials: D
authors.lastname: Waterson
authors.forename: Francisco-Javier
authors.initials: FJ
authors.lastname: Gamo
authors.forename: Laura M
authors.initials: LM
authors.lastname: Sanz
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: Hailong
authors.initials: H
authors.lastname: Wang
authors.forename: Han
authors.initials: H
authors.lastname: Cui
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D005461:Fluorine / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D001896:Boron Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005461:Fluorine; C512998:tavaborole