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]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]benzaze‐pinium chloride (7), 1,2,5,6‐tetrahydro‐4H‐imidazo[1′,2′:1,6]pyrimido[5,4‐d]benzazepines 10a‐e, 2,3,6,7‐tetrahydro‐1H 5H‐pyrimido[1′,2′:1,6]pyrimido[5,4‐d]benzazepine (11), and 1,2,5,6‐tetrahydro‐4H‐thiazolo‐[3′,2′:1,6]pyrimido[5,4‐d]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]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.
ASJC Scopus subject areas
- Organic Chemistry