Synthesis of 1-and 3-(1-Substituted 4-Piperidinyl)-1, 2, 3, 4-tetrahydro-2-oxoquinazolines as Potential Antihypertensive Agents

• Published in: Chem. Pharm. Bull Vol. 33; no. 3; pp. 1116 - 1128
• Main Authors: TAKAI, HARUKI, SHUTO, KATSUICHI, TERANISHI, MASAYUKI, KUBO, KAZUHIRO, KASUYA, YUTAKA, KARASHIMA, NAOKO, OBASE, HIROYUKI, NAKAMIZO, NOBUHIRO, SHIGENOBU, KOKI, HASHIKAMI, MAKIKO
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 1985; 公益社団法人日本薬学会; Japan Science and Technology Agency
• Subjects: alpha adrenergic blocking; Animals; antihypertensive activity; Antihypertensive Agents - chemical synthesis; Blood Pressure - drug effects; Heart Rate - drug effects; Male; piperidine; Piperidines - chemical synthesis; Piperidines - pharmacology; quinazoline; Quinazolines - chemical synthesis; Quinazolines - pharmacology; Rats; Rats, Inbred SHR; Rats, Inbred Strains; reductive cleavage; Structure-Activity Relationship
• ISSN: 0009-2363; 1347-5223; 1347-5223
• DOI: 10.1248/cpb.33.1116

A series of 1-and 3-(1-substituted 4-piperidinyl)-1, 2, 3, 4-tetrahydro-2-oxoquinazolines were synthesized and tested for antihypertensive activity. Among the compounds tested, 1-(2-hydroxy-2-phenethyl)-4-(1, 2, 3, 4-tetrahydro-2-oxo-3-quinazolinyl) piperidine derivatives were generally the most effective in lowering blood pressure in the spontaneous hypertensive rat model. Of these, 1-[2-(4-chlorophenyl)-2-hydroxyethyl]-4-(1, 2, 3, 4-tetrahydro-2-oxo-3-quinazolinyl) piperidine (26) (KF5908) seemed the most promising.