Novel ‘soft’ β-blockers as potential safe antiglaucoma agents
Novel ‘soft’ β-blockers as potential safe antiglaucoma agents
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新型“软”β-受体阻滞剂作为潜在安全的抗青光眼药物
DOI：
10.3109/02713688809031786
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发表时间：
1988
影响因子：
2
通讯作者：
A. Elkoussi
中科院分区：
文献类型：
--
作者：
N. Bodor;A. Elkoussi
基于“非活性代谢物法”设计合成了一系列新型的“软”β阻断剂。因此，美托洛尔的酸性代谢产物被转化为各种亲脂酸酯。以超短效B-肾上腺素能拮抗剂“艾司洛尔”为参比化合物，测试了新化合物对兔眼内压的影响。与参照物甲酯相比，大多数受试化合物显示出更高的降压活性和更持久的降压活性。金刚烷乙酯2被认为是最有潜力的眼科抗青光眼药物。该化合物表现出有效和持久的降眼压活性，对眼睛没有局部刺激。同时，它在人体血液中显示出很快的水解率(t1/2=7.0min)为非活性的酸性代谢物。这使得有效地将所需的眼活动与不需要的全身性3-阻断动作分离成为可能。单侧治疗2例。
A series of novel “soft” β-blockers was designed and synthesized based on the “inactive metabolite approach”. Accordingly, the acidic metabolite of metoprolol was converted into various lipophilic esters. The new compounds were tested for their effect on the intraocular pressure (IOP) of rabbits using the ultra-short acting B-adrenergic antagonist “Esmolol®” as a reference compound. Most of the tested compounds displayed a higher and a more prolonged ocular hypotensive activity than the reference methyl ester. The adamantaneethyl ester 2 emerged as the best potential candidate for ophthalmic use as an antiglaucoma agent. This compound exhibited an effective and long lasting ocular hypotensive activity without local irritation to the eye. At the same time, it showed a very fast rate of hydrolysis in human blood (t1/2= 7.0 minutes) to the inactive acid metabolite. This makes possible effective separation of the desired ocular activity from unwanted systemic 3-blocking action. Unilateral treatment with 2 pro...