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A series of 1-aminoalkyl-pyrrolo[2,3-c]azepin-8-one derivatives was synthesized and evaluated as alpha 1 adrenergic and serotonin 2 (5-HT2) receptor antagonists, with the aim of finding a novel antihypertensive agent potently exhibiting both activities. Some compounds with a 4-[4-(4-fluorobenzoyl)piperidino]butyl group at the 1-position exhibited both activities, and varied significantly in terms of the substituents at the 4-position of the pyrroloazepine ring. Among the compounds obtained in this study, (E)-1-[4-[4-(4-fluorobenzoyl)piperidino]-butyl]-4-hydroxyimino-7- methyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-c]azepin-8-one (15a, SUN9221) displayed potent alpha 1-adrenergic antagonistic activity (pA2 = 8.89 +/- 0.21) and 5-HT2 antagonistic activity (pA2 = 8.74 +/- 0.22) in isolated guinea pig arteries. This compound exhibited antihypertensive activity and a duration of action equivalent to orally administered prazosin or doxazosin, 3 mg/kg, in conscious spontaneously hypertensive rats, as well as potent antiplatelet aggregation activity.

Two new alkaloids possessing a cyclobutane ring, named pipercyclobutanamides A ( 1 ) and B ( 2 ), have been isolated from the fruits of Piper nigrum. Their stereostructures were determined by extensive spectroscopic methods.

The English teachers at Showa Women's University Junior and Senior High Schools, Tokyo, have been searching for a more efficient English-teaching method for a long time. We are using a ‘team teaching’ programme to motivate the students to learn to use English in their school environment. This particular scheme involves two teachers, teaching simultaneously in these same classroom. Each team is made up of one Japanese teacher of English and one native speaker. Our students are 13 and 14 years old and are junior high school first graders.