title: Optimization of a pyrazole hit from FBDD into a novel series of indazoles as ketohexokinase inhibitors.
abstract: A series of indazoles have been discovered as KHK inhibitors from a pyrazole hit identified through fragment-based drug discovery (FBDD). The optimization process guided by both X-ray crystallography and solution activity resulted in lead-like compounds with good pharmaceutical properties.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, Welsh & McKean Roads, PO Box 776, Spring House, PA 19477, United States. xzhang5@its.jnj.com
authors.forename: Xuqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Fengbing
authors.initials: F
authors.lastname: Song
authors.forename: Gee-Hong
authors.initials: GH
authors.lastname: Kuo
authors.forename: Amy
authors.initials: A
authors.lastname: Xiang
authors.forename: Alan C
authors.initials: AC
authors.lastname: Gibbs
authors.forename: Marta C
authors.initials: MC
authors.lastname: Abad
authors.forename: Weimei
authors.initials: W
authors.lastname: Sun
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Kuo
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Sui
mesh_terms: D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D005631:Fructokinases / Q000037:antagonists & inhibitors*; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D007191:Indazoles; D011720:Pyrazoles; C031280:pyrazole; D005631:Fructokinases; C021475:ketohexokinase