微波辅助合成 3-羟基-2-氧吲哚并化合物及其抗青光眼活性的初步评价。

Microwave-Assisted Synthesis of 3-Hydroxy-2-oxindoles and Pilot Evaluation of Their Antiglaucomic Activity.

机构信息

Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia.

Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (IPAC RAS), Chernogolovka 142432, Russia.

出版信息

Int J Mol Sci. 2023 Mar 7;24(6):5101. doi: 10.3390/ijms24065101.

Glaucoma is a widespread neurodegenerative disease for which increased intraocular pressure (IOP) is a primary modifiable risk factor. Recently, we have observed that compounds with oxindole scaffolds are involved in the regulation of intraocular pressure and therefore have potential antiglaucomic activity. In this article, we present an efficient method for obtaining novel 2-oxindole derivatives via microwave-assisted (MW) decarboxylative condensation of substituted isatins with malonic and cyanoacetic acids. Various 3-hydroxy-2-oxindoles were synthesized using MW activation for 5-10 min with high yields (up to 98%). The influence of novel compounds applied in instillations on IOP was studied in vivo on normotensive rabbits. The lead compound was found to reduce the IOP by 5.6 Torr (ΔIOP for the widely used antiglaucomatousic drug timolol 3.5 Torr and for melatonin 2.7 Torr).

青光眼是一种广泛存在的神经退行性疾病，其中眼内压（IOP）升高是主要的可调节风险因素。最近，我们观察到具有吲哚酮骨架的化合物参与了眼压的调节，因此具有潜在的抗青光眼活性。在本文中，我们提出了一种通过微波辅助（MW）脱羧缩合取代的色酮与丙二酸和氰基乙酸来获得新型 2-吲哚酮衍生物的有效方法。使用 MW 激活，各种 3-羟基-2-吲哚酮在 5-10 分钟内以高产率（高达 98%）合成。在正常眼压的兔体内研究了新型化合物滴眼对眼压的影响。发现先导化合物可使眼压降低 5.6 托（与广泛使用的抗青光眼药物噻吗洛尔 3.5 托和褪黑素 2.7 托相比，ΔIOP）。