title: The optimization of pyridazinone series of glucan synthase inhibitors.
abstract: A detailed structure-activity relationship study of a novel series of pyridazine-based small molecule glucan synthase inhibitors is described. The optimization of the PK profile of this series led to the discovery of compound 11g, which demonstrated in vivo potency ip in a lethal fungal infection model.
authors: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA. rongze.kuang@merck.com
authors: Rongze
authors: R
authors: Kuang
authors: Heping
authors: H
authors: Wu
authors: Pauline C
authors: PC
authors: Ting
authors: Robert G
authors: RG
authors: Aslanian
authors: Jianhua
authors: J
authors: Cao
authors: David W
authors: DW
authors: Kim
authors: Joe F
authors: JF
authors: Lee
authors: John
authors: J
authors: Schwerdt
authors: Gang
authors: G
authors: Zhou
authors: R Jason
authors: RJ
authors: Herr
authors: Andrew J
authors: AJ
authors: Zych
authors: Jinhai
authors: J
authors: Yang
authors: Sang Q
authors: SQ
authors: Lam
authors: David M
authors: DM
authors: Jenkins
authors: Samuel A
authors: SA
authors: Sakwa
authors: Samuel
authors: S
authors: Wainhaus
authors: Todd A
authors: TA
authors: Black
authors: Anthony
authors: A
authors: Cacciapuoti
authors: Paul M
authors: PM
authors: McNicholas
authors: Yiming
authors: Y
authors: Xu
authors: Scott S
authors: SS
authors: Walker
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006207:Half-Life; D051379:Mice; D008826:Microbial Sensitivity Tests; D011724:Pyridazines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D011724:Pyridazines; D013449:Sulfonamides; D005964:Glucosyltransferases; C040232:glucan synthase