Conformationally restricted congeners of hypotensive and platelet aggregation inhibitors: 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones derived from 5H-indeno[1,2-c]pyridazine
A number of 7-amino and 7-acylamino substituted 4,4a-dihydro-5H-indeno[1,2-c]pyridazin-3-ones have been synthesized as rigid congeners of hypotensive 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones and tested as antihypertensive, antithrombotic, antiulcer, and antiinflammatory agents. Unlike the pre...
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| Veröffentlicht in: | Journal of medicinal chemistry 1986-11, Vol.29 (11), p.2191-2194 |
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| container_issue | 11 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 29 |
| creator | Cignarella, Giorgio Barlocco, Daniela Pinna, Gerard A Loriga, Mario Tofanetti, Odoardo Germini, Mauro Sala, Franca |
| description | A number of 7-amino and 7-acylamino substituted 4,4a-dihydro-5H-indeno[1,2-c]pyridazin-3-ones have been synthesized as rigid congeners of hypotensive 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones and tested as antihypertensive, antithrombotic, antiulcer, and antiinflammatory agents. Unlike the previously described 7-cyano derivative, which displayed only antiinflammatory action, the new series exhibited significant antihypertensive and antithrombotic properties. In this respect, the 7-amino (2b) and the 7-acetylamino (2c) derivatives were found to be the most potent and long lasting in reducing the blood pressure in spontaneously hypertensive rats and in protecting mice from the induction of thrombosis. These compounds, as well as the 7-(2-chloropropionyl) derivative 2d, also exhibited antiinflammatory activity; in addition, 2c,d were highly effective in inhibiting indomethacin-induced ulcers in the rat. |
| doi_str_mv | 10.1021/jm00161a010 |
| format | Article |
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Unlike the previously described 7-cyano derivative, which displayed only antiinflammatory action, the new series exhibited significant antihypertensive and antithrombotic properties. In this respect, the 7-amino (2b) and the 7-acetylamino (2c) derivatives were found to be the most potent and long lasting in reducing the blood pressure in spontaneously hypertensive rats and in protecting mice from the induction of thrombosis. These compounds, as well as the 7-(2-chloropropionyl) derivative 2d, also exhibited antiinflammatory activity; in addition, 2c,d were highly effective in inhibiting indomethacin-induced ulcers in the rat.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00161a010</identifier><identifier>PMID: 3783580</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Animals ; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Anti-Ulcer Agents - chemical synthesis ; Anti-Ulcer Agents - pharmacology ; Antihypertensive Agents - chemical synthesis ; Antihypertensive Agents - pharmacology ; Chemistry ; Exact sciences and technology ; Fibrinolytic Agents - chemical synthesis ; Fibrinolytic Agents - pharmacology ; Guinea Pigs ; Heterocyclic compounds ; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings ; In Vitro Techniques ; Male ; Mice ; Organic chemistry ; Platelet Aggregation - drug effects ; Preparations and properties ; Pyridazines - chemical synthesis ; Pyridazines - pharmacology ; Rats ; Rats, Inbred Strains ; Structure-Activity Relationship</subject><ispartof>Journal of medicinal chemistry, 1986-11, Vol.29 (11), p.2191-2194</ispartof><rights>1987 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a383t-eda6246598954fec81430e50b0cdd4625d6adafb67c065dac7b35b66dbc265d43</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm00161a010$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00161a010$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7928136$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3783580$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cignarella, Giorgio</creatorcontrib><creatorcontrib>Barlocco, Daniela</creatorcontrib><creatorcontrib>Pinna, Gerard A</creatorcontrib><creatorcontrib>Loriga, Mario</creatorcontrib><creatorcontrib>Tofanetti, Odoardo</creatorcontrib><creatorcontrib>Germini, Mauro</creatorcontrib><creatorcontrib>Sala, Franca</creatorcontrib><title>Conformationally restricted congeners of hypotensive and platelet aggregation inhibitors: 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones derived from 5H-indeno[1,2-c]pyridazine</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>A number of 7-amino and 7-acylamino substituted 4,4a-dihydro-5H-indeno[1,2-c]pyridazin-3-ones have been synthesized as rigid congeners of hypotensive 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones and tested as antihypertensive, antithrombotic, antiulcer, and antiinflammatory agents. Unlike the previously described 7-cyano derivative, which displayed only antiinflammatory action, the new series exhibited significant antihypertensive and antithrombotic properties. In this respect, the 7-amino (2b) and the 7-acetylamino (2c) derivatives were found to be the most potent and long lasting in reducing the blood pressure in spontaneously hypertensive rats and in protecting mice from the induction of thrombosis. These compounds, as well as the 7-(2-chloropropionyl) derivative 2d, also exhibited antiinflammatory activity; in addition, 2c,d were highly effective in inhibiting indomethacin-induced ulcers in the rat.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Anti-Ulcer Agents - chemical synthesis</subject><subject>Anti-Ulcer Agents - pharmacology</subject><subject>Antihypertensive Agents - chemical synthesis</subject><subject>Antihypertensive Agents - pharmacology</subject><subject>Chemistry</subject><subject>Exact sciences and technology</subject><subject>Fibrinolytic Agents - chemical synthesis</subject><subject>Fibrinolytic Agents - pharmacology</subject><subject>Guinea Pigs</subject><subject>Heterocyclic compounds</subject><subject>Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Mice</subject><subject>Organic chemistry</subject><subject>Platelet Aggregation - drug effects</subject><subject>Preparations and properties</subject><subject>Pyridazines - chemical synthesis</subject><subject>Pyridazines - pharmacology</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Structure-Activity Relationship</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1986</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkUtv1DAUhS0EKkNhxRrJC8RD1OBH7GTYlYF2QJVAomxAyHLsmxlPEzu1M4jwr_iHpMxoxIKVr3U-nfs4CD1k9CWjnL3adJQyxQxl9BaaMckpKSpa3EYzSjknXHFxF93LeUMpFYyLI3QkykrIis7Q70UMTUydGXwMpm1HnCAPydsBHLYxrCBAyjg2eD32cYCQ_Q_AJjjct2aAFgZsVqsEq78G2Ie1r_0QU36NFTFpbIkkHQzrqShOJHF-PboUiXjGl89JPybvzC8fYoCMHaTJ2-EmxQ7LJfHBQYjf2Akn9vsBhfvoTmPaDA_27zH6cvbucrEkFx_P3y9OL4gRlRgIOKN4oeS8msuiAVuxQlCQtKbWuUJx6ZRxpqlVaamSztiyFrJWytWWT_9CHKMnO98-xevtdBTd-WyhbU2AuM26LFlZzpWawBc70KaYc4JG98l30-6aUX0TkP4noIl-tLfd1h24A7tPZNIf73WTrWmbZIL1-YCVc14xcdOU7DCfB_h5kE260qoUpdSXnz7rD7R4e3729Y3mE_90xxub9SZu0xR2_u-AfwDIrraT</recordid><startdate>19861101</startdate><enddate>19861101</enddate><creator>Cignarella, Giorgio</creator><creator>Barlocco, Daniela</creator><creator>Pinna, Gerard A</creator><creator>Loriga, Mario</creator><creator>Tofanetti, Odoardo</creator><creator>Germini, Mauro</creator><creator>Sala, Franca</creator><general>American Chemical Society</general><scope>BSCLL</scope><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>19861101</creationdate><title>Conformationally restricted congeners of hypotensive and platelet aggregation inhibitors: 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones derived from 5H-indeno[1,2-c]pyridazine</title><author>Cignarella, Giorgio ; Barlocco, Daniela ; Pinna, Gerard A ; Loriga, Mario ; Tofanetti, Odoardo ; Germini, Mauro ; Sala, Franca</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a383t-eda6246598954fec81430e50b0cdd4625d6adafb67c065dac7b35b66dbc265d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1986</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Anti-Ulcer Agents - chemical synthesis</topic><topic>Anti-Ulcer Agents - pharmacology</topic><topic>Antihypertensive Agents - chemical synthesis</topic><topic>Antihypertensive Agents - pharmacology</topic><topic>Chemistry</topic><topic>Exact sciences and technology</topic><topic>Fibrinolytic Agents - chemical synthesis</topic><topic>Fibrinolytic Agents - pharmacology</topic><topic>Guinea Pigs</topic><topic>Heterocyclic compounds</topic><topic>Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Mice</topic><topic>Organic chemistry</topic><topic>Platelet Aggregation - drug effects</topic><topic>Preparations and properties</topic><topic>Pyridazines - chemical synthesis</topic><topic>Pyridazines - pharmacology</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cignarella, Giorgio</creatorcontrib><creatorcontrib>Barlocco, Daniela</creatorcontrib><creatorcontrib>Pinna, Gerard A</creatorcontrib><creatorcontrib>Loriga, Mario</creatorcontrib><creatorcontrib>Tofanetti, Odoardo</creatorcontrib><creatorcontrib>Germini, Mauro</creatorcontrib><creatorcontrib>Sala, Franca</creatorcontrib><collection>Istex</collection><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>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cignarella, Giorgio</au><au>Barlocco, Daniela</au><au>Pinna, Gerard A</au><au>Loriga, Mario</au><au>Tofanetti, Odoardo</au><au>Germini, Mauro</au><au>Sala, Franca</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Conformationally restricted congeners of hypotensive and platelet aggregation inhibitors: 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones derived from 5H-indeno[1,2-c]pyridazine</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1986-11-01</date><risdate>1986</risdate><volume>29</volume><issue>11</issue><spage>2191</spage><epage>2194</epage><pages>2191-2194</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>A number of 7-amino and 7-acylamino substituted 4,4a-dihydro-5H-indeno[1,2-c]pyridazin-3-ones have been synthesized as rigid congeners of hypotensive 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones and tested as antihypertensive, antithrombotic, antiulcer, and antiinflammatory agents. Unlike the previously described 7-cyano derivative, which displayed only antiinflammatory action, the new series exhibited significant antihypertensive and antithrombotic properties. In this respect, the 7-amino (2b) and the 7-acetylamino (2c) derivatives were found to be the most potent and long lasting in reducing the blood pressure in spontaneously hypertensive rats and in protecting mice from the induction of thrombosis. These compounds, as well as the 7-(2-chloropropionyl) derivative 2d, also exhibited antiinflammatory activity; in addition, 2c,d were highly effective in inhibiting indomethacin-induced ulcers in the rat.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>3783580</pmid><doi>10.1021/jm00161a010</doi><tpages>4</tpages></addata></record> |
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| ispartof | Journal of medicinal chemistry, 1986-11, Vol.29 (11), p.2191-2194 |
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| subjects | Animals Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis Anti-Inflammatory Agents, Non-Steroidal - pharmacology Anti-Ulcer Agents - chemical synthesis Anti-Ulcer Agents - pharmacology Antihypertensive Agents - chemical synthesis Antihypertensive Agents - pharmacology Chemistry Exact sciences and technology Fibrinolytic Agents - chemical synthesis Fibrinolytic Agents - pharmacology Guinea Pigs Heterocyclic compounds Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings In Vitro Techniques Male Mice Organic chemistry Platelet Aggregation - drug effects Preparations and properties Pyridazines - chemical synthesis Pyridazines - pharmacology Rats Rats, Inbred Strains Structure-Activity Relationship |
| title | Conformationally restricted congeners of hypotensive and platelet aggregation inhibitors: 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones derived from 5H-indeno[1,2-c]pyridazine |
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