title: Pharmacophore identification, synthesis, and biological evaluation of carboxylated chalcone derivatives as CysLT1 antagonists.
abstract: The pharmacophore model (Hypo1) with a well prediction capacity for CysLT(1) antagonists was developed using Catalyst/HypoGen program. Virtual screening against an in-house database consisted of carboxylated chalcones using Hypo1 was performed. Retrieved hits 26a, 26b, 27a, and 27b were synthesized and biological evaluated, the results of which demonstrated that these compounds showed moderate to good CysLT(1) antagonistic activities. This study indicated that the generated model (Hypo1) is a reliable and useful tool in lead optimization for novel CysLT(1) antagonists.
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Dong
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Xueqin
authors.initials: X
authors.lastname: Huang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Erqing
authors.initials: E
authors.lastname: Wei
authors.forename: Lilin
authors.initials: L
authors.lastname: Du
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Yongzhou
authors.initials: Y
authors.lastname: Hu
mesh_terms: D045744:Cell Line, Tumor; D002599:Chalcone / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020024:Leukotriene Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D018077:Receptors, Leukotriene / Q000737:chemistry* / Q000378:metabolism
chemical_list: D020024:Leukotriene Antagonists; D018077:Receptors, Leukotriene; D002599:Chalcone; C083169:leukotriene D4 receptor