title: Hapten synthesis for (+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5-tet rahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] triazolo[4,3-a][1,4]diazepine (E6123).
abstract: (+)-6-(2-Chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4, 5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f]triazolo[4,3-a] [1,4]diazepine (E6123) is a very potent platelet-activating factor (PAF) receptor antagonist and shows potent anti-PAF activities at the microgram level in a variety of animal models. In order to examine the pharmacokinetics of E6123 at low doses, establishment of a radioimmunoassay is required. On the basis of the metabolic pattern of E6123, we synthesized 6-[2-chloro-4-(3-carboxypropyl) phenyl]-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5-tetrahydro-8H -pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine 22 as a potential hapten. In the synthesis of 22, we developed butynyl carbamate as a piperidine ring N-protecting group to prevent possible side reaction, namely oxidation of the methylene at position 2. This protecting group is stable under usual basic and acidic conditions.
authors.affiliation: Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Miyazawa
authors.forename: K
authors.initials: K
authors.lastname: Okano
authors.forename: T
authors.initials: T
authors.lastname: Kawahara
authors.forename: Y
authors.initials: Y
authors.lastname: Machida
authors.forename: I
authors.initials: I
authors.lastname: Yamatsu
mesh_terms: D001381:Azepines / Q000276:immunology*; D002845:Chromatography; D006241:Haptens / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011863:Radioimmunoassay; D014230:Triazoles / Q000276:immunology*
chemical_list: D001381:Azepines; D006241:Haptens; D010972:Platelet Activating Factor; D014230:Triazoles; C068033:E 6123