Evaluation of synthetic naphthalene derivatives as novel chemical chaperones that mimic 4-phenylbutyric acid.
Evaluation of synthetic naphthalene derivatives as novel chemical chaperones that mimic 4-phenylbutyric acid.
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评估合成萘衍生物作为模拟 4-苯基丁酸的新型化学伴侣。
DOI：
10.1016/j.bmcl.2014.12.080
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Hamana H.
中科院分区：
文献类型：
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作者：
Mimori S;Koshikawa Y;Mashima Y;Mitsunaga K;Kawada K;Kaneko M;Okuma Y;Nomura Y;Murakami Y;Kanzaki T;Hamana H.
化学伴侣4-苯基丁酸（4-PBA）具有作为治疗神经退行性疾病的药剂的潜力。然而，高浓度的要求保证了临床使用的化学优化。在这项研究中，新的萘衍生物具有更大的化学伴侣活性比4-PBA的合成与类似的苯环。所有新化合物均具有化学伴侣活性，其中2和5具有较高的活性。在随后的实验中，在帕金森病模型细胞中检查了化合物的保护作用，并且9和11的低毒性与萘的两亲性取代有关。
The chemical chaperone 4-phenylbutyric acid (4-PBA) has potential as an agent for the treatment of neurodegenerative diseases. However, the requirement of high concentrations warrants chemical optimization for clinical use. In this study, novel naphthalene derivatives with a greater chemical chaperone activity than 4-PBA were synthesized with analogy to the benzene ring. All novel compounds showed chemical chaperone activity, and2and5possessed high activity. In subsequent experiments, the protective effects of the compounds were examined in Parkinson’s disease model cells, and low toxicity of9and11was related to amphiphilic substitution with naphthalene.