title: Design, synthesis and biological activity evaluation of desloratadine analogues as H1 receptor antagonists.
abstract: A series of N-substituted desloratadine analogues were designed and synthesized. They were tested for H1 antihistamine activity by inhibiting histamine-induced contraction of isolated ileum muscles of guinea-pigs in vitro and inhibiting histamine-induced asthmatic reaction in guinea-pigs in vivo. All the evaluated compounds exhibited significant antihistamine activity compared with desloratadine. Five active compounds induced no sedative effects on mouse and four of them exhibited lower anticholinergic side effects than desloratadine. Among these analogues, compound 10, (1S,4S)-4-chlorocyclohexyl desloratadine displayed the highest activity and best safety profile. And it was believed to be a potential candidate as the 3rd generation antihistamine.
authors.affiliation: Institute of Chemical Industry of Forest Products, CAF, Nanjing 210042, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Sima
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Wang
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Cao
authors.forename: Li-Gong
authors.initials: LG
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
mesh_terms: D000818:Animals; D015195:Drug Design; D004355:Drug Stability; D057809:HEK293 Cells; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017336:Loratadine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D011485:Protein Binding / Q000187:drug effects
chemical_list: D006634:Histamine H1 Antagonists; D017336:Loratadine; C121345:desloratadine