Mimori Seisuke, Koshikawa Yukari, Mashima Yu, Mitsunaga Katsuyoshi, Kawada Koichi, Kaneko Masayuki, Okuma Yasunobu, Nomura Yasuyuki, Murakami Yasuoki, Kanzaki Tetsuto, Hamana Hiroshi
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomicho, Choshi, Chiba 288-0025, Japan.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomicho, Choshi, Chiba 288-0025, Japan.
Bioorg Med Chem Lett. 2015 Feb 15;25(4):811-4. doi: 10.1016/j.bmcl.2014.12.080. Epub 2015 Jan 5.
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, and 2 and 5 possessed high activity. In subsequent experiments, the protective effects of the compounds were examined in Parkinson's disease model cells, and low toxicity of 9 and 11 was related to amphiphilic substitution with naphthalene.
化学伴侣4-苯基丁酸（4-PBA）有潜力作为治疗神经退行性疾病的药物。然而，高浓度的需求促使其进行化学优化以用于临床。在本研究中，通过类比苯环合成了具有比4-PBA更高化学伴侣活性的新型萘衍生物。所有新型化合物均表现出化学伴侣活性，其中2号和5号具有高活性。在后续实验中，在帕金森病模型细胞中检测了这些化合物的保护作用，9号和11号的低毒性与萘的两亲性取代有关。
