Synthesis and Biological Activity of Novel 5-(ω-Aryloxyalkyl)oxazole Derivatives as Brain-Derived Neurotrophic Factor Inducers

Tsuyoshi Maekawa; Nozomu Sakai; Hiroyuki Tawada; Katsuhito Murase; Masatoshi Hazama; Yasuo Sugiyama; Yu Momose

doi:10.1248/cpb.51.565

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Synthesis and Biological Activity of Novel 5-(ω-Aryloxyalkyl)oxazole Derivatives as Brain-Derived Neurotrophic Factor Inducers

Tsuyoshi Maekawa, Nozomu Sakai, Hiroyuki Tawada, Katsuhito Murase, Masatoshi Hazama, Yasuo Sugiyama, Yu Momose

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Keywords: 5-(ω-aryloxyalkyl)oxazole, brain-derived neurotrophic factor, diabetic neuropathy, diabetic complication, streptozotocin (STZ)-diabetic rat

JOURNAL FREE ACCESS

2003 Volume 51 Issue 5 Pages 565-573

DOI https://doi.org/10.1248/cpb.51.565

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Abstract

A novel series of 5-(ω-aryloxyalkyl)oxazole derivatives was prepared and their effects on brain-derived neurotrophic factor (BDNF) production were evaluated in human neuroblastoma (SK-N-SH) cells. Syntheses were performed by construction of an oxazole ring as a key reaction. Most of the 5-(ω-aryloxyalkyl)oxazole derivatives markedly increased BDNF production in SK-N-SH cells. 4-(4-Chlorophenyl)-2-(2-methyl-1H-imidazol-1-yl)-5-[3-(2-methoxyphenoxy)propyl]-1, 3-oxazole, one of the most promising compounds, showed potent activity (EC₅₀=7.9 μM) and the improvement of the motor nerve conduction velocity and the tail-flick response accompanied by a recovery of the brain-derived neurotrophic factor level in the sciatic nerve of streptozotocin (STZ)-diabetic rats.

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