title: Stereoselective synthesis of desloratadine derivatives as antagonist of histamine.
abstract: A series of desloratadine derivatives were stereoselectively synthesized and evaluated for H(1) antihistamine activity. For the evaluation of H(1) antihistamine activity, the in vitro histamine-induced contraction of the guinea-pig ileum assay (HC) was used. The synthesized desloratadine derivatives 7, 8 and 9 are structurally related to rupatadine and were generated by replacement of the 5-methyl-3-pyridine group of rupatadine with gamma-alkylidene butenolide. Their H(1) antihistamine activities have shown a high dependence on the exact nature of the substituent in the lactone ring. Optimum structures 7, 8a and 8g display potent activity inhibiting histamine-induced effects.
authors.affiliation: School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, PR China.
authors.forename: Gai-Zhi
authors.initials: GZ
authors.lastname: Liu
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Xu
authors.forename: Guang-Wei
authors.initials: GW
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Ya-Na
authors.initials: YN
authors.lastname: Wang
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Liu
authors.forename: De-Quan
authors.initials: DQ
authors.lastname: Yu
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D039563:Histamine H1 Antagonists, Non-Sedating / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D017336:Loratadine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008958:Models, Molecular; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
chemical_list: D039563:Histamine H1 Antagonists, Non-Sedating; D017336:Loratadine; C121345:desloratadine