Synthesis and biological activity of novel 5-(omega-aryloxyalkyl)oxazole derivatives as brain-derived neurotrophic factor inducers.
A novel series of 5-(omega-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-(omega-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 (EC(50)=7.9 microM) 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.
Maekawa
Tsuyoshi
T
Medicinal Chemistry Research Laboratories II, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan. Maekawa_Tsuyoshi@takeda.co.jp
Sakai
Nozomu
N
Tawada
Hiroyuki
H
Murase
Katsuhito
K
Hazama
Masatoshi
M
Sugiyama
Yasuo
Y
Momose
Yu
Y
D000473:Alkanes / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D001932:Brain Neoplasms / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D013347:Subcellular Fractions / Q000737:chemistry
D000473:Alkanes; D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D007202:Indicators and Reagents; D010080:Oxazoles