Synthesis and Biological Activities of Optical Isomers of 2-(4-Chlorophenyl)-5,6-dihydro-(1)benzothiepino(5,4-c)pyridazin-3(2H)-one 7-Oxide
| Autor: | Yasuto Morimoto, Kuniki Ikeda, Tohru Nakao, Nobuhiro Marubayashi, Yuko Yamaguchi, Minoru Obata |
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| Rok vydání: | 1992 |
| Předmět: |
Male
Stereochemistry Mice Inbred Strains Stereoisomerism Crystal structure Benzothiepins In Vitro Techniques Binding Competitive Conflict Psychological Mice chemistry.chemical_compound Drug Discovery Animals Diazepam binding Absolute configuration Rats Inbred Strains Sulfoxide General Chemistry General Medicine Receptors GABA-A Rats Pyridazines Anti-Anxiety Agents chemistry Cumene hydroperoxide Reagent Anticonvulsants Enantiomer |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 40:117-121 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.40.117 |
| Popis: | Two enantiomers of 2-(4-chlorophenyl)-5,6-dihydro-(1)benzothiepino[5,4- c]pyridazin-3(2H)-one 7-oxide ((+/-)-1: Y-23684) were synthesized in high yields by asymmetric oxidation of the synthetic precursor (2) using modified Sharpless reagent. Among the oxidants tested, cumene hydroperoxide (CHP) gave the highest optical and chemical yields, while tert-butyl, tert-amyl, and 1,1,3,3-tetramethylbutyl hydroperoxides did not show such high enantio-selectivities. The absolute configuration of (+)-1 enantiomer synthesized from 2, Ti(O-iso-Pr)4, (-)-diethyl tartarate, and CHP was determined to be S by X-ray crystallographic analysis. Both enantiomers, S-(+)-1 and R-(-)-1, and (+/-)-1 had approximately equivalent in vivo activities to antibicuculline test in mice and anticonflict test in rats, although S-( + )-1 showed about three times higher affinity to benzodiazepine receptor than R-(-)-1 in [3H]diazepam binding assay. |
| Databáze: | OpenAIRE |
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