title: Synthesis and antihypertensive activity of 4-(diazabicyclo[4.1.0]-heptenyloxy)benzopyran derivatives and their analogues.
abstract: A series of 3,4-dihydro-3-hydroxy-4-[(5-oxo-3,4-diazabicyclo[4.1.0]hept- 2-en-2-yl)oxy]-2H-1-benzopyrans and their analogues were synthesized and evaluated on potassium channel opening and hypotensive activities. Compound (-)-13B with a (4-methyl-5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yl)oxy group for the 4-position of the benzopyran ring was 3 times as potent as EMD 57283 (II), the lead compound, in hypotensive activity. The results would demonstrate that 5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yloxy moieties are effective as the substituents at the 4-position of benzopyran-type potassium channel openers.
authors.affiliation: New Product Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Horino
authors.forename: T
authors.initials: T
authors.lastname: Mimura
authors.forename: K
authors.initials: K
authors.lastname: Kagechika
authors.forename: M
authors.initials: M
authors.lastname: Ohta
authors.forename: H
authors.initials: H
authors.lastname: Kubo
authors.forename: M
authors.initials: M
authors.lastname: Kitagawa
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D019806:Cromakalim / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000959:Antihypertensive Agents; D001578:Benzopyrans; D001643:Bridged Bicyclo Compounds; C107488:EMD 57283; D015221:Potassium Channels; D011724:Pyridazines; D019806:Cromakalim