Manoury P M, Binet J L, Rousseau J, Lefèvre-Borg F, Cavero I G
J Med Chem. 1987 Jun;30(6):1003-11. doi: 10.1021/jm00389a008.
A series of para-substituted phenoxypropanolamines has been synthesized and tested for beta-adrenoceptor blocking activity. Some derivatives (8, 11, 12, 20, 21) exhibited greater in vitro potency than the reference drugs metoprolol and propranolol. This series, in contrast to propranolol but similar to metoprolol, possesses cardioselectivity. The 3-[p-[(cycloalkylmethoxy)ethyl]phenoxy]-1-substituted-amino-2-prop anol derivatives 8 (cyclopropylmethoxyethyl: betaxolol) and 11 (cyclobutylmethoxyethyl) produced antihypertensive effects in spontaneously hypertensive rats. Betaxolol (Kerlon, 8) was found to exhibit an appropriate preclinical pharmacological and human pharmacokinetic profile (elevated oral bioavailability and prolonged plasma half-life) for the treatment of chronic cardiovascular diseases such as hypertension and angina.
已合成了一系列对-取代苯氧基丙醇胺，并对其β-肾上腺素受体阻断活性进行了测试。一些衍生物（8、11、12、20、21）在体外表现出比参比药物美托洛尔和普萘洛尔更高的效力。与普萘洛尔不同但与美托洛尔相似，该系列具有心脏选择性。3-[对-[(环烷基甲氧基)乙基]苯氧基]-1-取代氨基-2-丙醇衍生物8（环丙基甲氧基乙基：倍他洛尔）和11（环丁基甲氧基乙基）在自发性高血压大鼠中产生了降压作用。发现倍他洛尔（凯尔朗，8）具有适用于治疗慢性心血管疾病如高血压和心绞痛的临床前药理学和人体药代动力学特征（口服生物利用度提高和血浆半衰期延长）。
