Synthesis and Biological Activity of Novel 5-(ω-Aryloxyalkyl)oxazole Derivatives as Brain-Derived Neurotrophic Factor Inducers
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-aryloxy...
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| Veröffentlicht in: | Chemical & Pharmaceutical Bulletin 2003, Vol.51(5), pp.565-573 |
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| creator | Maekawa, Tsuyoshi Sakai, Nozomu Tawada, Hiroyuki Murase, Katsuhito Hazama, Masatoshi Sugiyama, Yasuo Momose, Yu |
| description | 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. |
| doi_str_mv | 10.1248/cpb.51.565 |
| format | Article |
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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.</description><identifier>ISSN: 0009-2363</identifier><identifier>EISSN: 1347-5223</identifier><identifier>DOI: 10.1248/cpb.51.565</identifier><identifier>PMID: 12736457</identifier><identifier>CODEN: CPBTAL</identifier><language>eng</language><publisher>Tokyo: The Pharmaceutical Society of Japan</publisher><subject>5-(ω-aryloxyalkyl)oxazole ; Alkanes - chemical synthesis ; Alkanes - pharmacology ; Animals ; Biological and medical sciences ; Blood Glucose - metabolism ; Body Weight - drug effects ; Brain Chemistry - drug effects ; Brain Neoplasms - metabolism ; brain-derived neurotrophic factor ; Brain-Derived Neurotrophic Factor - biosynthesis ; Cell Line, Tumor ; Diabetes Mellitus, Experimental - complications ; diabetic complication ; Diabetic Neuropathies - drug therapy ; diabetic neuropathy ; General and cellular metabolism. Vitamins ; Humans ; Indicators and Reagents ; Magnetic Resonance Spectroscopy ; Male ; Medical sciences ; Miscellaneous ; Neural Conduction - drug effects ; Neuroblastoma - metabolism ; Neuropharmacology ; Oxazoles - chemical synthesis ; Oxazoles - pharmacology ; Pharmacology. Drug treatments ; Rats ; Rats, Sprague-Dawley ; Reaction Time - drug effects ; Stimulation, Chemical ; streptozotocin (STZ)-diabetic rat ; Structure-Activity Relationship ; Subcellular Fractions - chemistry</subject><ispartof>Chemical and Pharmaceutical Bulletin, 2003, Vol.51(5), pp.565-573</ispartof><rights>2003 The Pharmaceutical Society of Japan</rights><rights>2003 INIST-CNRS</rights><rights>Copyright Japan Science and Technology Agency 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c689t-322466668905a28089c2f2d259878396eebfa0da40660471a569c76ed0576af13</citedby><cites>FETCH-LOGICAL-c689t-322466668905a28089c2f2d259878396eebfa0da40660471a569c76ed0576af13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1883,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14875753$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12736457$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maekawa, Tsuyoshi</creatorcontrib><creatorcontrib>Sakai, Nozomu</creatorcontrib><creatorcontrib>Tawada, Hiroyuki</creatorcontrib><creatorcontrib>Murase, Katsuhito</creatorcontrib><creatorcontrib>Hazama, Masatoshi</creatorcontrib><creatorcontrib>Sugiyama, Yasuo</creatorcontrib><creatorcontrib>Momose, Yu</creatorcontrib><creatorcontrib>aMedicinal Chemistry Research Laboratories II</creatorcontrib><creatorcontrib>Takeda Chemical Industries</creatorcontrib><creatorcontrib>bPharmacology Research Laboratories II</creatorcontrib><creatorcontrib>dStrategic Product Planning Department</creatorcontrib><creatorcontrib>Ltd</creatorcontrib><creatorcontrib>Pharmaceutical Research Division</creatorcontrib><creatorcontrib>Pharmaceutical Production Division</creatorcontrib><creatorcontrib>cChemical Development Laboratories</creatorcontrib><title>Synthesis and Biological Activity of Novel 5-(ω-Aryloxyalkyl)oxazole Derivatives as Brain-Derived Neurotrophic Factor Inducers</title><title>Chemical & Pharmaceutical Bulletin</title><addtitle>Chem. Pharm. Bull.</addtitle><description>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.</description><subject>5-(ω-aryloxyalkyl)oxazole</subject><subject>Alkanes - chemical synthesis</subject><subject>Alkanes - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - metabolism</subject><subject>Body Weight - drug effects</subject><subject>Brain Chemistry - drug effects</subject><subject>Brain Neoplasms - metabolism</subject><subject>brain-derived neurotrophic factor</subject><subject>Brain-Derived Neurotrophic Factor - biosynthesis</subject><subject>Cell Line, Tumor</subject><subject>Diabetes Mellitus, Experimental - complications</subject><subject>diabetic complication</subject><subject>Diabetic Neuropathies - drug therapy</subject><subject>diabetic neuropathy</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Humans</subject><subject>Indicators and Reagents</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Neural Conduction - drug effects</subject><subject>Neuroblastoma - metabolism</subject><subject>Neuropharmacology</subject><subject>Oxazoles - chemical synthesis</subject><subject>Oxazoles - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reaction Time - drug effects</subject><subject>Stimulation, Chemical</subject><subject>streptozotocin (STZ)-diabetic rat</subject><subject>Structure-Activity Relationship</subject><subject>Subcellular Fractions - chemistry</subject><issn>0009-2363</issn><issn>1347-5223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkdFu0zAUhiMEYmVwwwOgSAgESCnHdmwnV6gbbEyaxgVwbbnOyerixp2dVAs3XPN0vBIurVoJSz6W7O_8_5H_LHtOYEpoWb036_mUkykX_EE2IayUBaeUPcwmAFAXlAl2kj2JcQlAOUj2ODshVDJRcjnJfn0du36B0cZcd01-Zr3zt9Zol89Mbze2H3Pf5jd-gy7nxZs_v4tZGJ2_H7X7Mbq3_l7_9A7zjxjsRqcGTDoxPwvadsW_S2zyGxyC74NfL6zJL7TpfcivumYwGOLT7FGrXcRn-_M0-37x6dv55-L6y-XV-ey6MKKq-4JRWoq0qhq4phVUtaEtbSivK1mxWiDOWw2NLkEIKCXRXNRGCmyAS6Fbwk6z1zvddfB3A8ZerWw06Jzu0A9RSZYMOIgEvvwPXPohdGk2RUoBLDnCVu7djjLBxxiwVetgVzqMioDahqJSKIoTlUJJ8Iu95DBfYXNE9ykk4NUe0DF9fRt0Z2w8cmUlueQscZc7LqlsM_Kdsx0eBzRRmgWurKIATAFwAlwBSTuNkYpkBGRZl1vHDzulZez1LR6sdOitcXiYfl9S9-FloYPCjv0FfKnBwQ</recordid><startdate>2003</startdate><enddate>2003</enddate><creator>Maekawa, Tsuyoshi</creator><creator>Sakai, Nozomu</creator><creator>Tawada, Hiroyuki</creator><creator>Murase, Katsuhito</creator><creator>Hazama, Masatoshi</creator><creator>Sugiyama, Yasuo</creator><creator>Momose, Yu</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Maruzen</general><general>Japan Science and Technology Agency</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>2003</creationdate><title>Synthesis and Biological Activity of Novel 5-(ω-Aryloxyalkyl)oxazole Derivatives as Brain-Derived Neurotrophic Factor Inducers</title><author>Maekawa, Tsuyoshi ; Sakai, Nozomu ; Tawada, Hiroyuki ; Murase, Katsuhito ; Hazama, Masatoshi ; Sugiyama, Yasuo ; Momose, Yu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c689t-322466668905a28089c2f2d259878396eebfa0da40660471a569c76ed0576af13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>5-(ω-aryloxyalkyl)oxazole</topic><topic>Alkanes - chemical synthesis</topic><topic>Alkanes - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - metabolism</topic><topic>Body Weight - drug effects</topic><topic>Brain Chemistry - drug effects</topic><topic>Brain Neoplasms - metabolism</topic><topic>brain-derived neurotrophic factor</topic><topic>Brain-Derived Neurotrophic Factor - biosynthesis</topic><topic>Cell Line, Tumor</topic><topic>Diabetes Mellitus, Experimental - complications</topic><topic>diabetic complication</topic><topic>Diabetic Neuropathies - drug therapy</topic><topic>diabetic neuropathy</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Humans</topic><topic>Indicators and Reagents</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Neural Conduction - drug effects</topic><topic>Neuroblastoma - metabolism</topic><topic>Neuropharmacology</topic><topic>Oxazoles - chemical synthesis</topic><topic>Oxazoles - pharmacology</topic><topic>Pharmacology. 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Pharm. Bull.</addtitle><date>2003</date><risdate>2003</risdate><volume>51</volume><issue>5</issue><spage>565</spage><epage>573</epage><pages>565-573</pages><issn>0009-2363</issn><eissn>1347-5223</eissn><coden>CPBTAL</coden><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. 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| subjects | 5-(ω-aryloxyalkyl)oxazole Alkanes - chemical synthesis Alkanes - pharmacology Animals Biological and medical sciences Blood Glucose - metabolism Body Weight - drug effects Brain Chemistry - drug effects Brain Neoplasms - metabolism brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - biosynthesis Cell Line, Tumor Diabetes Mellitus, Experimental - complications diabetic complication Diabetic Neuropathies - drug therapy diabetic neuropathy General and cellular metabolism. Vitamins Humans Indicators and Reagents Magnetic Resonance Spectroscopy Male Medical sciences Miscellaneous Neural Conduction - drug effects Neuroblastoma - metabolism Neuropharmacology Oxazoles - chemical synthesis Oxazoles - pharmacology Pharmacology. Drug treatments Rats Rats, Sprague-Dawley Reaction Time - drug effects Stimulation, Chemical streptozotocin (STZ)-diabetic rat Structure-Activity Relationship Subcellular Fractions - chemistry |
| title | Synthesis and Biological Activity of Novel 5-(ω-Aryloxyalkyl)oxazole Derivatives as Brain-Derived Neurotrophic Factor Inducers |
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