title: The synthesis and structure-activity relationship of pyridazinones as glucan synthase inhibitors.
abstract: A structure-activity relationship study of the lead 5-[4-(benzylsulfonyl)piperazin-1-yl]-4-morpholino-2-phenyl-pyridazin-3(2H)-one 1 has resulted in the identification of 2-(3,5-difluorophenyl)-4-(3-fluorocyclopentyloxy)-5-[4-(isopropylsulfonyl)piperazin-1-yl]-pyridazin-3(2H)-one 11c as a β-1,3-glucan synthase inhibitor. Compound 11c exhibited significant efficacy in an in vivo mouse model of Candida glabrata infection.
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, Kenilworth, NJ 07033, USA. pauline.ting@merck.com
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Ting
authors.forename: Rongze
authors.initials: R
authors.lastname: Kuang
authors.forename: Heping
authors.initials: H
authors.lastname: Wu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Aslanian
authors.forename: Jianhua
authors.initials: J
authors.lastname: Cao
authors.forename: David W
authors.initials: DW
authors.lastname: Kim
authors.forename: Joe F
authors.initials: JF
authors.lastname: Lee
authors.forename: John
authors.initials: J
authors.lastname: Schwerdt
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
authors.forename: Samuel
authors.initials: S
authors.lastname: Wainhaus
authors.forename: Todd A
authors.initials: TA
authors.lastname: Black
authors.forename: Anthony
authors.initials: A
authors.lastname: Cacciapuoti
authors.forename: Paul M
authors.initials: PM
authors.lastname: McNicholas
authors.forename: Yiming
authors.initials: Y
authors.lastname: Xu
authors.forename: Scott S
authors.initials: SS
authors.lastname: Walker
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011724:Pyridazines; D005964:Glucosyltransferases; C040232:glucan synthase