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新型1-(1H-吲哚-4-氧基)-3-(2-(2-甲氧基苯氧基)乙氨基)丙-2-醇类似物的合成与药理活性

Synthesis and Pharmacological Activity of a New Series of 1-(1H-Indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol Analogs.

作者信息

Bednarski Marek, Otto Monika, Dudek Magdalena, Kołaczkowski Marcin, Bucki Adam, Siwek Agata, Groszek Grażyna, Maziarz Elżbieta, Wilk Piotr, Sapa Jacek

机构信息

Faculty of Pharmacy, Department of Pharmacological Screening, Medical College, Jagiellonian University, Krakow, Poland.

Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Medical College, Jagiellonian University, Krakow, Poland.

出版信息

Arch Pharm (Weinheim). 2016 Mar;349(3):211-23. doi: 10.1002/ardp.201500234. Epub 2016 Feb 8.

Abstract

β-Adrenergic receptor antagonists are important therapeutics for the treatment of cardiovascular disorders. In the group of β-blockers, much attention is being paid to the third-generation drugs that possess important ancillary properties besides inhibiting β-adrenoceptors. Vasodilating activity of these drugs is produced through different mechanisms, such as nitric oxide (NO) release, β2 -agonistic action, α1 -blockade, antioxidant action, and Ca(2+) entry blockade. Here, a study on evaluation of the cardiovascular activity of five new compounds is presented. Compound 3a is a methyl and four of the tested compounds (3b-e) are dimethoxy derivatives of 1-(1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol. The obtained results confirmed that the methyl and dimethoxy derivatives of 1-(1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol and their enantiomers possess α1 - and β1 -adrenolytic activities and that the antiarrhythmic and hypotensive effects of the tested compounds are related to their adrenolytic properties.

摘要

β-肾上腺素能受体拮抗剂是治疗心血管疾病的重要药物。在β受体阻滞剂组中,第三代药物备受关注,这些药物除了抑制β-肾上腺素能受体外,还具有重要的辅助特性。这些药物的血管舒张活性通过不同机制产生,如一氧化氮(NO)释放、β2-激动作用、α1-阻滞、抗氧化作用和钙(2+)内流阻滞。在此,介绍一项对五种新化合物心血管活性的评估研究。化合物3a是甲基化合物,其余四种受试化合物(3b - e)是1-(1H-吲哚-4-氧基)-3-(2-(2-甲氧基苯氧基)乙氨基)丙-2-醇的二甲氧基衍生物。所得结果证实,1-(1H-吲哚-4-氧基)-3-(2-(2-甲氧基苯氧基)乙氨基)丙-2-醇的甲基和二甲氧基衍生物及其对映体具有α1和β1肾上腺素能阻断活性,且受试化合物的抗心律失常和降压作用与其肾上腺素能阻断特性有关。

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