Polycyclic N‐heterocyclic compounds. XLI. Synthesis of 4‐substituted 6,7‐dihydro‐5H‐pyrimido[5,4‐d][1]benzazepines, 1,2,5,6‐tetrahydro‐4H‐imidazo[1′,2′:1,6]pyrimido[5,4‐d][1]benzazepines and their related compounds as a series of potential blood platelet aggregation inhibitors

Tomohisa Nagamatsu, Yoshiji Hantani, Minoru Yamada, Kenji Sasaki, Hiromi Ohtomo, Taiji Nakayama, Takashi Hirota

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8 Citations (Scopus)

Abstract

As a series of polyheterocyclic compounds for exploitation as anti‐platelet agents, tricyclic heterocyclic compounds, 4‐substituted 6,7‐dihydro‐5H‐pyrimido[5,4‐d][1]benzazepines 3–6, 9, 12–14, and 16–26, having nitrogen, oxygen, or sulfur containing functional groups at the 4‐position, were prepared. In addition, tetra‐cyclic heterocyclic compounds, 3‐methyl‐1,2,5,6‐tetrahydro‐4H‐imidazo[1′,2′:1,6]pyrimido[5,4‐d][1]benzaze‐pinium chloride (7), 1,2,5,6‐tetrahydro‐4H‐imidazo[1′,2′:1,6]pyrimido[5,4‐d][1]benzazepines 10a‐e, 2,3,6,7‐tetrahydro‐1H 5H‐pyrimido[1′,2′:1,6]pyrimido[5,4‐d][1]benzazepine (11), and 1,2,5,6‐tetrahydro‐4H‐thiazolo‐[3′,2′:1,6]pyrimido[5,4‐d][1]benzazepinium chloride (15) via ring closure of 4‐(hydroxyalkylamino)‐ 6, 9a‐e, and 3c, and 4‐(2‐hydroxyethylthio)‐6,7‐dihydro‐5H‐pyrimido[5,4‐d][1]benzazepine (14) with phosphoryl chloride or thionyl chloride, respectively, were also prepared. Their inhibitory activities against collagen‐induced aggregation of rabbit blood platelets in vitro were investigated. Among them, compound 5 having a morpholino group at the 4‐position on the tricyclic nucleus, which enhanced the activity more than 14‐fold as compared with aspirin, was found to have the most satisfactory in inhibitory activity.

Original languageEnglish
Pages (from-to)193-202
Number of pages10
JournalJournal of Heterocyclic Chemistry
Volume30
Issue number1
DOIs
Publication statusPublished - Jan 1 1993

ASJC Scopus subject areas

  • Organic Chemistry

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