- Design, synthesis and anticonvulsant-analgesic activity of new N-[(phenoxy)alkyl]- and N-[(phenoxy)ethoxyethyl]aminoalkanols
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New derivatives of N-[(phenoxy)alkyl]- and N-[(phenoxy)ethoxyethyl]aminoalkanols have been synthesized and evaluated for their anticonvulsant activity in maximal electroshock (MES), maximal electroshock seizure threshold (MEST), and pentylenetetrazol (PTZ) tests. Their neurotoxicity was evaluated via rotarod and chimney tests. The compounds exhibiting the most beneficial activity and protection indices were evaluated for analgesic activity using the formalin test for neurogenic pain. They were also evaluated for their influence on cytotoxic activity using in vitro cellular models (HepG2 and CRL-2534 cell lines). Experiments performed using MTT and neutral red cytotoxicity assays showed that all evaluated compounds were safe for normal, glial cells (astrocytes) and did not induce hepatotoxic effects. Based on the results from the in vitro studies, the safety of the evaluated compounds was inferred. The most promising compound in this research was 1-{2-[2-(2,3-dimethylphenoxy)ethoxy]ethyl}piperidin-3-ol hydrochloride. Additionally, in silico metabolism prediction for the compound has been performed.
- Rapacz, Anna,Waszkielewicz, Anna M.,Pańczyk, Katarzyna,Pytka, Karolina,Koczurkiewicz, Paulina,Piska, Kamil,P?kala, El?bieta,Budziszewska, Bogus?awa,Starek-?wiechowicz, Beata,Marona, Henryk
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p. 220 - 238
(2017/02/05)
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- Discovery of 1-aryloxyethyl piperazine derivatives as Kv1.5 potassium channel inhibitors (part I)
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Kv1.5 potassium channel is an efficacious and safe therapeutic target for the treatment of atrial fibrillation (AF), the most common arrhythmia that threatens human. Herein, by modifying the hit compound 7k from an in-house database, 48 derivatives were synthesized for the assay of their Kv1.5 inhibitory effects by whole cell patch clamp technique. Six compounds which showed better potency than the positive compound dronedarone were selected for the next evaluation of their drug-like properties. Compound 8 exhibited balanced solubility and permeability. It also showed acceptable pharmacodynamics profile with very low acute toxicity. Taking all these data into account, compound 8 can serve as a promising lead for the development of novel therapeutic agent for the treatment of AF.
- Guo, Xiaoke,Ma, Xianglei,Yang, Qian,Xu, Jing,Huang, Lu,Jia, Jianmin,Shan, Jiaojiao,Liu, Li,Chen, Weilin,Chu, Hongxi,Wei, Jinlian,Zhang, Xiaojin,Sun, Haopeng,Tang, Yiqun,You, Qidong
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supporting information
p. 89 - 94
(2014/06/09)
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- A simple modification of the known preparation procedure of 2-Phenoxyethyl bromides providing high yields
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A modification of preparation method was developed for synthesis of a number of 1-bromo-2-phenoxyethanes from 1,2-dibromoethanes and sodium phenolates in two-phase water-organic system with or without addition of triethylbenzylammonium chloride as phase-transfer catalyst. Addition of NaOH in two portions for transforming phenols into phenolates ensured high yields (60-80%) of phenoxylation products.
- Slyn'ko,Tormyshev
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p. 254 - 257
(2007/10/03)
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