Synthesis and biological activity of novel α-substituted β-phenylpropionic acids having pyridin-2-ylphenyl moiety as antihyperglycemic agents
Graphic We previously reported the identification of novel oximes having 5-benzyl-2,4-thiazolidinedione with antihyperglycemic activity. We now report the synthesis and biological activity of a novel series of oximes and amides having α-substituted-β-phenylpropionic acids. In this series, we obtaine...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2004-05, Vol.12 (9), p.2419-2439 |
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| container_title | Bioorganic & medicinal chemistry |
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| creator | Takamura, Makoto Sakurai, Mitsuya Yamada, Eriko Fujita, Sachie Yachi, Makoto Takagi, Toshiyuki Isobe, Aya Hagisawa, Yuka Fujiwara, Toshihiko Yanagisawa, Hiroaki |
| description | Graphic
We previously reported the identification of novel oximes having 5-benzyl-2,4-thiazolidinedione with antihyperglycemic activity. We now report the synthesis and biological activity of a novel series of oximes and amides having α-substituted-β-phenylpropionic acids. In this series, we obtained potent PPARα/γ dual agonist (
S)-
9d, with which activation of PPARα and PPARγ was considerably more potent than that of the reference compounds GW9578
22 and rosiglitazone
3, respectively. This means (
S)-
9d is of the strongest class of PPARα/γ dual agonists. In the course of this study, we also obtained
8h, which indicated potent plasma glucose lowering effect in spite of weak PPARα/γ agonistic activity. |
| doi_str_mv | 10.1016/j.bmc.2004.01.048 |
| format | Article |
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We previously reported the identification of novel oximes having 5-benzyl-2,4-thiazolidinedione with antihyperglycemic activity. We now report the synthesis and biological activity of a novel series of oximes and amides having α-substituted-β-phenylpropionic acids. In this series, we obtained potent PPARα/γ dual agonist (
S)-
9d, with which activation of PPARα and PPARγ was considerably more potent than that of the reference compounds GW9578
22 and rosiglitazone
3, respectively. This means (
S)-
9d is of the strongest class of PPARα/γ dual agonists. In the course of this study, we also obtained
8h, which indicated potent plasma glucose lowering effect in spite of weak PPARα/γ agonistic activity.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2004.01.048</identifier><identifier>PMID: 15080938</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Antihyperglycemic agent ; Base Sequence ; Biological and medical sciences ; Cell Line, Tumor ; DNA Primers ; General and cellular metabolism. Vitamins ; Humans ; Hypoglycemic Agents - chemical synthesis ; Hypoglycemic Agents - chemistry ; Hypoglycemic Agents - pharmacology ; KK mouse ; Medical sciences ; Peroxisome Proliferator-Activated Receptors - agonists ; Pharmacology. Drug treatments ; Phenylpropionates - chemical synthesis ; Phenylpropionates - chemistry ; Phenylpropionates - pharmacology ; PPARα ; PPARγ ; Pyridines - chemical synthesis ; Pyridines - chemistry ; Pyridines - pharmacology ; Spectrum Analysis</subject><ispartof>Bioorganic & medicinal chemistry, 2004-05, Vol.12 (9), p.2419-2439</ispartof><rights>2004 Elsevier Ltd</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-1cbcc619a6ec4426dd7953306397e257d5a250ac55769a116bf5970d59c6a5863</citedby><cites>FETCH-LOGICAL-c381t-1cbcc619a6ec4426dd7953306397e257d5a250ac55769a116bf5970d59c6a5863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0968089604001166$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15683538$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15080938$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takamura, Makoto</creatorcontrib><creatorcontrib>Sakurai, Mitsuya</creatorcontrib><creatorcontrib>Yamada, Eriko</creatorcontrib><creatorcontrib>Fujita, Sachie</creatorcontrib><creatorcontrib>Yachi, Makoto</creatorcontrib><creatorcontrib>Takagi, Toshiyuki</creatorcontrib><creatorcontrib>Isobe, Aya</creatorcontrib><creatorcontrib>Hagisawa, Yuka</creatorcontrib><creatorcontrib>Fujiwara, Toshihiko</creatorcontrib><creatorcontrib>Yanagisawa, Hiroaki</creatorcontrib><title>Synthesis and biological activity of novel α-substituted β-phenylpropionic acids having pyridin-2-ylphenyl moiety as antihyperglycemic agents</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>Graphic
We previously reported the identification of novel oximes having 5-benzyl-2,4-thiazolidinedione with antihyperglycemic activity. We now report the synthesis and biological activity of a novel series of oximes and amides having α-substituted-β-phenylpropionic acids. In this series, we obtained potent PPARα/γ dual agonist (
S)-
9d, with which activation of PPARα and PPARγ was considerably more potent than that of the reference compounds GW9578
22 and rosiglitazone
3, respectively. This means (
S)-
9d is of the strongest class of PPARα/γ dual agonists. In the course of this study, we also obtained
8h, which indicated potent plasma glucose lowering effect in spite of weak PPARα/γ agonistic activity.</description><subject>Antihyperglycemic agent</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>DNA Primers</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Humans</subject><subject>Hypoglycemic Agents - chemical synthesis</subject><subject>Hypoglycemic Agents - chemistry</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>KK mouse</subject><subject>Medical sciences</subject><subject>Peroxisome Proliferator-Activated Receptors - agonists</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenylpropionates - chemical synthesis</subject><subject>Phenylpropionates - chemistry</subject><subject>Phenylpropionates - pharmacology</subject><subject>PPARα</subject><subject>PPARγ</subject><subject>Pyridines - chemical synthesis</subject><subject>Pyridines - chemistry</subject><subject>Pyridines - pharmacology</subject><subject>Spectrum Analysis</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2O1DAUhCMEYpqBA7BB3sAuwU5iJxYrNBp-pJFYAGvLsV-6Xyuxg-1uKafgLHCQORPu6ZZgxeptvqpXqiqKl4xWjDLxdl8Ns6lqStuKsoq2_aNiw1rRlk0j2eNiQ6XoS9pLcVU8i3FPKa1byZ4WV4zTnsqm3xQ_v64u7SBiJNpZMqCf_BaNnog2CY-YVuJH4vwRJnL_q4yHISZMhwSW3P8ulx24dVqCX9A7NFmDNpKdPqLbkmUNaNGVdZmRB5DMHiE76tOzhLt1gbCdVgPzSbsFl-Lz4smopwgvLve6-P7h9tvNp_Luy8fPN-_vStP0LJXMDMYIJrUA07a1sLaTvGmoaGQHNe8s1zWn2nDeCakZE8PIZUctl0Zo3ovmunhz9s3hfxwgJjVjNDBN2oE_RNWxnklBWQbZGTTBxxhgVEvAWYdVMapOK6i9yiuo0wqKMpVXyJpXF_PDMIP9q7jUnoHXF0DH3PUYtDMY_-FE3_AH7t2Zg1zFESGoaBCcAYsBTFLW439i_AG47ql1</recordid><startdate>20040501</startdate><enddate>20040501</enddate><creator>Takamura, Makoto</creator><creator>Sakurai, Mitsuya</creator><creator>Yamada, Eriko</creator><creator>Fujita, Sachie</creator><creator>Yachi, Makoto</creator><creator>Takagi, Toshiyuki</creator><creator>Isobe, Aya</creator><creator>Hagisawa, Yuka</creator><creator>Fujiwara, Toshihiko</creator><creator>Yanagisawa, Hiroaki</creator><general>Elsevier Ltd</general><general>Elsevier Science</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>7X8</scope></search><sort><creationdate>20040501</creationdate><title>Synthesis and biological activity of novel α-substituted β-phenylpropionic acids having pyridin-2-ylphenyl moiety as antihyperglycemic agents</title><author>Takamura, Makoto ; Sakurai, Mitsuya ; Yamada, Eriko ; Fujita, Sachie ; Yachi, Makoto ; Takagi, Toshiyuki ; Isobe, Aya ; Hagisawa, Yuka ; Fujiwara, Toshihiko ; Yanagisawa, Hiroaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-1cbcc619a6ec4426dd7953306397e257d5a250ac55769a116bf5970d59c6a5863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Antihyperglycemic agent</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>DNA Primers</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Humans</topic><topic>Hypoglycemic Agents - chemical synthesis</topic><topic>Hypoglycemic Agents - chemistry</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>KK mouse</topic><topic>Medical sciences</topic><topic>Peroxisome Proliferator-Activated Receptors - agonists</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenylpropionates - chemical synthesis</topic><topic>Phenylpropionates - chemistry</topic><topic>Phenylpropionates - pharmacology</topic><topic>PPARα</topic><topic>PPARγ</topic><topic>Pyridines - chemical synthesis</topic><topic>Pyridines - chemistry</topic><topic>Pyridines - pharmacology</topic><topic>Spectrum Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takamura, Makoto</creatorcontrib><creatorcontrib>Sakurai, Mitsuya</creatorcontrib><creatorcontrib>Yamada, Eriko</creatorcontrib><creatorcontrib>Fujita, Sachie</creatorcontrib><creatorcontrib>Yachi, Makoto</creatorcontrib><creatorcontrib>Takagi, Toshiyuki</creatorcontrib><creatorcontrib>Isobe, Aya</creatorcontrib><creatorcontrib>Hagisawa, Yuka</creatorcontrib><creatorcontrib>Fujiwara, Toshihiko</creatorcontrib><creatorcontrib>Yanagisawa, Hiroaki</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takamura, Makoto</au><au>Sakurai, Mitsuya</au><au>Yamada, Eriko</au><au>Fujita, Sachie</au><au>Yachi, Makoto</au><au>Takagi, Toshiyuki</au><au>Isobe, Aya</au><au>Hagisawa, Yuka</au><au>Fujiwara, Toshihiko</au><au>Yanagisawa, Hiroaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and biological activity of novel α-substituted β-phenylpropionic acids having pyridin-2-ylphenyl moiety as antihyperglycemic agents</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2004-05-01</date><risdate>2004</risdate><volume>12</volume><issue>9</issue><spage>2419</spage><epage>2439</epage><pages>2419-2439</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>Graphic
We previously reported the identification of novel oximes having 5-benzyl-2,4-thiazolidinedione with antihyperglycemic activity. We now report the synthesis and biological activity of a novel series of oximes and amides having α-substituted-β-phenylpropionic acids. In this series, we obtained potent PPARα/γ dual agonist (
S)-
9d, with which activation of PPARα and PPARγ was considerably more potent than that of the reference compounds GW9578
22 and rosiglitazone
3, respectively. This means (
S)-
9d is of the strongest class of PPARα/γ dual agonists. In the course of this study, we also obtained
8h, which indicated potent plasma glucose lowering effect in spite of weak PPARα/γ agonistic activity.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>15080938</pmid><doi>10.1016/j.bmc.2004.01.048</doi><tpages>21</tpages></addata></record> |
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| subjects | Antihyperglycemic agent Base Sequence Biological and medical sciences Cell Line, Tumor DNA Primers General and cellular metabolism. Vitamins Humans Hypoglycemic Agents - chemical synthesis Hypoglycemic Agents - chemistry Hypoglycemic Agents - pharmacology KK mouse Medical sciences Peroxisome Proliferator-Activated Receptors - agonists Pharmacology. Drug treatments Phenylpropionates - chemical synthesis Phenylpropionates - chemistry Phenylpropionates - pharmacology PPARα PPARγ Pyridines - chemical synthesis Pyridines - chemistry Pyridines - pharmacology Spectrum Analysis |
| title | Synthesis and biological activity of novel α-substituted β-phenylpropionic acids having pyridin-2-ylphenyl moiety as antihyperglycemic agents |
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