Kobayashi T, Inoue T, Nishino S, Fujihara Y, Oizumi K, Kimura T
Pharmaceutical Research Department, Ube Laboratory, Ube Industries, Ltd. Yamaguchi, Japan.
Chem Pharm Bull (Tokyo). 1995 May;43(5):797-817. doi: 10.1248/cpb.43.797.
Novel 2-amino-1,4-dihydropyridine derivatives I, which contain N,N,-dialkylaminoalkoxycarbonyl groups at the 3- and/or 5-position, were synthesized and their antihypertensive effects were evaluated in spontaneously hypertensive rats. Remarkably prolonged duration of antihypertensive action was observed when a tertiary amino group was introduced into either the 3- and/or 5-ester side-chain of the 1,4-dihydropyridine ring. In particular, the compounds containing cyclic amino moieties at the 3-position showed greater potency than those with acyclic amino moieties. Chemical modification studies indicated that the two ester side-chains of 1,4-dihydropyridine at the 3- and 5-position might function in a different manner in relation to the antihypertensive activities. 3-(1-Benzhydrylazetidinited potent and long-lasting antihypertensive effects with gradual onset of action, and is a promising candidate as an antihypertensive drug.
合成了在3位和/或5位含有N，N-二烷基氨基烷氧基羰基的新型2-氨基-1,4-二氢吡啶衍生物I，并在自发性高血压大鼠中评估了它们的降压作用。当将叔氨基引入1,4-二氢吡啶环的3位和/或5位酯侧链时，观察到降压作用的持续时间显著延长。特别是，在3位含有环状氨基部分的化合物比具有非环状氨基部分的化合物显示出更大的效力。化学修饰研究表明，1,4-二氢吡啶在3位和5位的两个酯侧链在降压活性方面可能以不同的方式起作用。3-(1-二苯甲基氮杂环丁烷)具有强效且持久的降压作用，起效逐渐，是一种有前景的抗高血压药物候选物。
