Studies on Anti-inflammatory Agents. V. Synthesis and Pharmacological Properties of 3-(Difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole and Related Compounds
A series of novel 1, 5-diphenylpyrazole derivatives bearing hydrophilic substituents was prepared. The anti-inflammatory and analgesic activities of these compounds were evaluated by using the adjuvant arthritis and Randall-Selitto assays in rats, and the structure-activity relationships were studie...
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| Veröffentlicht in: | Chemical & pharmaceutical bulletin 1997/09/15, Vol.45(9), pp.1475-1481 |
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| container_title | Chemical & pharmaceutical bulletin |
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| creator | TSUJI, Kiyoshi KONISHI, Nobukiyo SPEARS, Glen W. OGINO, Takashi NAKAMURA, Katsuya TOJO, Takashi OCHI, Takehiro SHIMOJO, Fumio SENOH, Hachiro MATSUO, Masaaki |
| description | A series of novel 1, 5-diphenylpyrazole derivatives bearing hydrophilic substituents was prepared. The anti-inflammatory and analgesic activities of these compounds were evaluated by using the adjuvant arthritis and Randall-Selitto assays in rats, and the structure-activity relationships were studied. The optimal compound was 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole (10) with oral ED50 values of 0.31 and 2.6 mg/kg on adjuvant-induced arthritis and carrageenin-induced foot edema, respectively. Compound 10 showed analgesic activities not only toward inflamed paw but also toward normal paw (ED30=0.55 and 1.8 mg/kg, respectively) in the Randall-Selitto assay, and moreover, 10 was effective in the tail-pinch assay (ED50=21 mg/kg) similarly to morphine. The asymmetric synthesis and pharmacological properties of the enantiomers of 10 are also reported. |
| doi_str_mv | 10.1248/cpb.45.1475 |
| format | Article |
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V. Synthesis and Pharmacological Properties of 3-(Difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole and Related Compounds</title><source>MEDLINE</source><source>J-STAGE (Japan Science & Technology Information Aggregator, Electronic) Freely Available Titles - Japanese</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Free Full-Text Journals in Chemistry</source><creator>TSUJI, Kiyoshi ; KONISHI, Nobukiyo ; SPEARS, Glen W. ; OGINO, Takashi ; NAKAMURA, Katsuya ; TOJO, Takashi ; OCHI, Takehiro ; SHIMOJO, Fumio ; SENOH, Hachiro ; MATSUO, Masaaki</creator><creatorcontrib>TSUJI, Kiyoshi ; KONISHI, Nobukiyo ; SPEARS, Glen W. ; OGINO, Takashi ; NAKAMURA, Katsuya ; TOJO, Takashi ; OCHI, Takehiro ; SHIMOJO, Fumio ; SENOH, Hachiro ; MATSUO, Masaaki</creatorcontrib><description>A series of novel 1, 5-diphenylpyrazole derivatives bearing hydrophilic substituents was prepared. The anti-inflammatory and analgesic activities of these compounds were evaluated by using the adjuvant arthritis and Randall-Selitto assays in rats, and the structure-activity relationships were studied. The optimal compound was 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole (10) with oral ED50 values of 0.31 and 2.6 mg/kg on adjuvant-induced arthritis and carrageenin-induced foot edema, respectively. Compound 10 showed analgesic activities not only toward inflamed paw but also toward normal paw (ED30=0.55 and 1.8 mg/kg, respectively) in the Randall-Selitto assay, and moreover, 10 was effective in the tail-pinch assay (ED50=21 mg/kg) similarly to morphine. The asymmetric synthesis and pharmacological properties of the enantiomers of 10 are also reported.</description><identifier>ISSN: 0009-2363</identifier><identifier>EISSN: 1347-5223</identifier><identifier>DOI: 10.1248/cpb.45.1475</identifier><identifier>PMID: 9332000</identifier><identifier>CODEN: CPBTAL</identifier><language>eng</language><publisher>Tokyo: The Pharmaceutical Society of Japan</publisher><subject>1, 5-diphenylpyrazole ; analgesic activity ; Analgesics ; Animals ; anti-inflammatory agent ; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis ; Anti-Inflammatory Agents, Non-Steroidal - chemistry ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Biological and medical sciences ; Chromatography, High Pressure Liquid ; Crystallography, X-Ray ; Magnetic Resonance Spectroscopy ; Male ; Mass Spectrometry ; Medical sciences ; Molecular Structure ; morphine ; Neuropharmacology ; Pharmacology. Drug treatments ; Pyrazoles - chemical synthesis ; Pyrazoles - chemistry ; Pyrazoles - pharmacology ; Rats ; Rats, Sprague-Dawley ; Structure-Activity Relationship ; Sulfoxides - chemical synthesis ; Sulfoxides - chemistry ; Sulfoxides - pharmacology</subject><ispartof>Chemical and Pharmaceutical Bulletin, 1997/09/15, Vol.45(9), pp.1475-1481</ispartof><rights>The Pharmaceutical Society of Japan</rights><rights>1998 INIST-CNRS</rights><rights>Copyright Japan Science and Technology Agency 1997</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1883,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2051348$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9332000$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>TSUJI, Kiyoshi</creatorcontrib><creatorcontrib>KONISHI, Nobukiyo</creatorcontrib><creatorcontrib>SPEARS, Glen W.</creatorcontrib><creatorcontrib>OGINO, Takashi</creatorcontrib><creatorcontrib>NAKAMURA, Katsuya</creatorcontrib><creatorcontrib>TOJO, Takashi</creatorcontrib><creatorcontrib>OCHI, Takehiro</creatorcontrib><creatorcontrib>SHIMOJO, Fumio</creatorcontrib><creatorcontrib>SENOH, Hachiro</creatorcontrib><creatorcontrib>MATSUO, Masaaki</creatorcontrib><title>Studies on Anti-inflammatory Agents. V. Synthesis and Pharmacological Properties of 3-(Difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole and Related Compounds</title><title>Chemical & pharmaceutical bulletin</title><addtitle>Chem. Pharm. Bull.</addtitle><description>A series of novel 1, 5-diphenylpyrazole derivatives bearing hydrophilic substituents was prepared. The anti-inflammatory and analgesic activities of these compounds were evaluated by using the adjuvant arthritis and Randall-Selitto assays in rats, and the structure-activity relationships were studied. The optimal compound was 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole (10) with oral ED50 values of 0.31 and 2.6 mg/kg on adjuvant-induced arthritis and carrageenin-induced foot edema, respectively. Compound 10 showed analgesic activities not only toward inflamed paw but also toward normal paw (ED30=0.55 and 1.8 mg/kg, respectively) in the Randall-Selitto assay, and moreover, 10 was effective in the tail-pinch assay (ED50=21 mg/kg) similarly to morphine. The asymmetric synthesis and pharmacological properties of the enantiomers of 10 are also reported.</description><subject>1, 5-diphenylpyrazole</subject><subject>analgesic activity</subject><subject>Analgesics</subject><subject>Animals</subject><subject>anti-inflammatory agent</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - chemistry</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Crystallography, X-Ray</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Molecular Structure</subject><subject>morphine</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyrazoles - chemical synthesis</subject><subject>Pyrazoles - chemistry</subject><subject>Pyrazoles - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Structure-Activity Relationship</subject><subject>Sulfoxides - chemical synthesis</subject><subject>Sulfoxides - chemistry</subject><subject>Sulfoxides - pharmacology</subject><issn>0009-2363</issn><issn>1347-5223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkkuLFDEUhQtRxnZ05VooUKRdpMyzHsumZ3zAgIOjbkSKVB7d1aSSmiQFlv9r_p_pqWYENwm55-PccM_NspcIFgjT-r0Yu4KyAtGKPcpWiNAKMIzJ42wFIWwAJiV5mj0L4QAhZrAiZ9lZQwhO4iq7u4mT7FXInc03Nvagt9rwYeDR-Tnf7JSNoch_FPnNbONehT7k3Mr8es_9wIUzbtcLbvJr70bl472RzglYX_TaTM67QcX9bN4BBNYUHB_u9zzulT3WGPhJwXohwmR0f6wu4q9x9vyPM-q-21dleFQy37phdJOV4Xn2RHMT1IvTfZ59_3D5bfsJXH35-Hm7uQIHTJoICIcaCVxWJRO1riiiTNZCElTqDkvZ6Ep0mJdEyQ5qUnONE4sFk5w2qq4ROc_eLr6jd7eTCrEd-iCUMdwqN4W2SnNkFDYJfP0feHCTt-lvLaIlJAimWBL16kRN3aBkO_p-4H5uT2kk_c1J5yFNVXtuRR8eMAxZcqkTdrFghxD5Tj3oPAUgjGrTPqCG1S1lbbMcx9X4J6fsWmXJX1l8soY</recordid><startdate>199709</startdate><enddate>199709</enddate><creator>TSUJI, Kiyoshi</creator><creator>KONISHI, Nobukiyo</creator><creator>SPEARS, Glen W.</creator><creator>OGINO, Takashi</creator><creator>NAKAMURA, Katsuya</creator><creator>TOJO, Takashi</creator><creator>OCHI, Takehiro</creator><creator>SHIMOJO, Fumio</creator><creator>SENOH, Hachiro</creator><creator>MATSUO, Masaaki</creator><general>The 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>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>199709</creationdate><title>Studies on Anti-inflammatory Agents. V. Synthesis and Pharmacological Properties of 3-(Difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole and Related Compounds</title><author>TSUJI, Kiyoshi ; KONISHI, Nobukiyo ; SPEARS, Glen W. ; OGINO, Takashi ; NAKAMURA, Katsuya ; TOJO, Takashi ; OCHI, Takehiro ; SHIMOJO, Fumio ; SENOH, Hachiro ; MATSUO, Masaaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j239t-3a0f1c26765c8f74145d8cd316fb2dd9f7cb2a63edb0f38af22672c5da49e8813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>1, 5-diphenylpyrazole</topic><topic>analgesic activity</topic><topic>Analgesics</topic><topic>Animals</topic><topic>anti-inflammatory agent</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - chemistry</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Crystallography, X-Ray</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Molecular Structure</topic><topic>morphine</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyrazoles - chemical synthesis</topic><topic>Pyrazoles - chemistry</topic><topic>Pyrazoles - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Structure-Activity Relationship</topic><topic>Sulfoxides - chemical synthesis</topic><topic>Sulfoxides - chemistry</topic><topic>Sulfoxides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>TSUJI, Kiyoshi</creatorcontrib><creatorcontrib>KONISHI, Nobukiyo</creatorcontrib><creatorcontrib>SPEARS, Glen W.</creatorcontrib><creatorcontrib>OGINO, Takashi</creatorcontrib><creatorcontrib>NAKAMURA, Katsuya</creatorcontrib><creatorcontrib>TOJO, Takashi</creatorcontrib><creatorcontrib>OCHI, Takehiro</creatorcontrib><creatorcontrib>SHIMOJO, Fumio</creatorcontrib><creatorcontrib>SENOH, Hachiro</creatorcontrib><creatorcontrib>MATSUO, Masaaki</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>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Chemical & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>TSUJI, Kiyoshi</au><au>KONISHI, Nobukiyo</au><au>SPEARS, Glen W.</au><au>OGINO, Takashi</au><au>NAKAMURA, Katsuya</au><au>TOJO, Takashi</au><au>OCHI, Takehiro</au><au>SHIMOJO, Fumio</au><au>SENOH, Hachiro</au><au>MATSUO, Masaaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Studies on Anti-inflammatory Agents. V. Synthesis and Pharmacological Properties of 3-(Difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole and Related Compounds</atitle><jtitle>Chemical & pharmaceutical bulletin</jtitle><addtitle>Chem. Pharm. Bull.</addtitle><date>1997-09</date><risdate>1997</risdate><volume>45</volume><issue>9</issue><spage>1475</spage><epage>1481</epage><pages>1475-1481</pages><issn>0009-2363</issn><eissn>1347-5223</eissn><coden>CPBTAL</coden><abstract>A series of novel 1, 5-diphenylpyrazole derivatives bearing hydrophilic substituents was prepared. The anti-inflammatory and analgesic activities of these compounds were evaluated by using the adjuvant arthritis and Randall-Selitto assays in rats, and the structure-activity relationships were studied. The optimal compound was 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole (10) with oral ED50 values of 0.31 and 2.6 mg/kg on adjuvant-induced arthritis and carrageenin-induced foot edema, respectively. Compound 10 showed analgesic activities not only toward inflamed paw but also toward normal paw (ED30=0.55 and 1.8 mg/kg, respectively) in the Randall-Selitto assay, and moreover, 10 was effective in the tail-pinch assay (ED50=21 mg/kg) similarly to morphine. The asymmetric synthesis and pharmacological properties of the enantiomers of 10 are also reported.</abstract><cop>Tokyo</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>9332000</pmid><doi>10.1248/cpb.45.1475</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0009-2363 |
| ispartof | Chemical and Pharmaceutical Bulletin, 1997/09/15, Vol.45(9), pp.1475-1481 |
| issn | 0009-2363 1347-5223 |
| language | eng |
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| source | MEDLINE; J-STAGE (Japan Science & Technology Information Aggregator, Electronic) Freely Available Titles - Japanese; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | 1, 5-diphenylpyrazole analgesic activity Analgesics Animals anti-inflammatory agent Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis Anti-Inflammatory Agents, Non-Steroidal - chemistry Anti-Inflammatory Agents, Non-Steroidal - pharmacology Biological and medical sciences Chromatography, High Pressure Liquid Crystallography, X-Ray Magnetic Resonance Spectroscopy Male Mass Spectrometry Medical sciences Molecular Structure morphine Neuropharmacology Pharmacology. Drug treatments Pyrazoles - chemical synthesis Pyrazoles - chemistry Pyrazoles - pharmacology Rats Rats, Sprague-Dawley Structure-Activity Relationship Sulfoxides - chemical synthesis Sulfoxides - chemistry Sulfoxides - pharmacology |
| title | Studies on Anti-inflammatory Agents. V. Synthesis and Pharmacological Properties of 3-(Difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole and Related Compounds |
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