Synthesis and biological activity of carboxylic acid replacement analogs of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline
The carboxylic acid group on the proline of 1 was replaced by a phosphoric acid, a hydroxamic acid, and a tetrazole to give compounds 2-4, respectively. Testing of 2-4 as angiotensin converting enzyme (ACE) inhibitors gave I50 values of 100, 1.6, and 22 microM, respectively, compared to 0.07 microM...
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| Veröffentlicht in: | Journal of medicinal chemistry 1985-08, Vol.28 (8), p.1067-1071 |
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| container_end_page | 1071 |
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| container_issue | 8 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 28 |
| creator | Almquist, Ronald G Chao, Wan Ru Jennings-White, Clive |
| description | The carboxylic acid group on the proline of 1 was replaced by a phosphoric acid, a hydroxamic acid, and a tetrazole to give compounds 2-4, respectively. Testing of 2-4 as angiotensin converting enzyme (ACE) inhibitors gave I50 values of 100, 1.6, and 22 microM, respectively, compared to 0.07 microM for 1. A hydroxamic acid derivative of the ketomethylene pentapeptide analogue 18 was then synthesized. This compound, 17, had an ACE I50 of 0.011 microM compared to 0.0076 microM for 18. Oral administration of 10 mg/kg of 17 to renal hypertensive rats had no effect on blood pressure or heart rate. |
| doi_str_mv | 10.1021/jm00146a015 |
| format | Article |
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Testing of 2-4 as angiotensin converting enzyme (ACE) inhibitors gave I50 values of 100, 1.6, and 22 microM, respectively, compared to 0.07 microM for 1. A hydroxamic acid derivative of the ketomethylene pentapeptide analogue 18 was then synthesized. This compound, 17, had an ACE I50 of 0.011 microM compared to 0.0076 microM for 18. Oral administration of 10 mg/kg of 17 to renal hypertensive rats had no effect on blood pressure or heart rate.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00146a015</identifier><identifier>PMID: 2991518</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Angiotensin-Converting Enzyme Inhibitors ; Animals ; Antihypertensive Agents - chemical synthesis ; Dipeptides - chemical synthesis ; Dipeptides - metabolism ; Dipeptides - pharmacology ; Hypertension, Renovascular - drug therapy ; Rats ; Structure-Activity Relationship</subject><ispartof>Journal of medicinal chemistry, 1985-08, Vol.28 (8), p.1067-1071</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a354t-ca7f73574a3295c3dc1d7d0dadc4b1a83dc01c3a94c55cea94f7abcde221100b3</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/jm00146a015$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00146a015$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2763,27075,27923,27924,56737,56787</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2991518$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Almquist, Ronald G</creatorcontrib><creatorcontrib>Chao, Wan Ru</creatorcontrib><creatorcontrib>Jennings-White, Clive</creatorcontrib><title>Synthesis and biological activity of carboxylic acid replacement analogs of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>The carboxylic acid group on the proline of 1 was replaced by a phosphoric acid, a hydroxamic acid, and a tetrazole to give compounds 2-4, respectively. Testing of 2-4 as angiotensin converting enzyme (ACE) inhibitors gave I50 values of 100, 1.6, and 22 microM, respectively, compared to 0.07 microM for 1. A hydroxamic acid derivative of the ketomethylene pentapeptide analogue 18 was then synthesized. This compound, 17, had an ACE I50 of 0.011 microM compared to 0.0076 microM for 18. Oral administration of 10 mg/kg of 17 to renal hypertensive rats had no effect on blood pressure or heart rate.</description><subject>Angiotensin-Converting Enzyme Inhibitors</subject><subject>Animals</subject><subject>Antihypertensive Agents - chemical synthesis</subject><subject>Dipeptides - chemical synthesis</subject><subject>Dipeptides - metabolism</subject><subject>Dipeptides - pharmacology</subject><subject>Hypertension, Renovascular - drug therapy</subject><subject>Rats</subject><subject>Structure-Activity Relationship</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkUuPEzEQhC0EWsLCiTOSTzyEDH6MZ5IjCruAFAlEFsHN6vE4iYPHHmxnleFH8RtxNNGKA6duVX1dfSiEnjL6hlHO3u57SllVA2XyHpoxySmp5rS6j2aUck54zcVD9CilPaVUMC4u0AVfLJhk8xn6sx593plkEwbf4dYGF7ZWg8Ogs721ecRhgzXENhxHZ3WRbYejGRxo0xufyxmUk3TCShAeQp7UrT1tyXqsg781MVu_xcb_HnuDrd_Z1uYQsXy5fkXaIkNvu0AqEo6B1GTYGT-6nTmCD6MjKzLE4Kw3j9GDDbhknpznJfp2fXWz_EhWnz98Wr5bERCyykRDs2mEbCoQfCG16DTrmo520OmqZTAvAmVawKLSUmpT5qaBVneGc8YobcUlej7llr-_DiZl1dukjXPgTTgk1dScSyl5AV9PoI4hpWg2aoi2hzgqRtWpHfVPO4V-do49tL3p7thzHcUnk29TNsc7G-JPVTeikermy1o16x_fl9VXrt4X_sXEg05qHw6xdJH--_kvd3Cq0g</recordid><startdate>198508</startdate><enddate>198508</enddate><creator>Almquist, Ronald G</creator><creator>Chao, Wan Ru</creator><creator>Jennings-White, Clive</creator><general>American Chemical Society</general><scope>BSCLL</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>198508</creationdate><title>Synthesis and biological activity of carboxylic acid replacement analogs of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline</title><author>Almquist, Ronald G ; Chao, Wan Ru ; Jennings-White, Clive</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a354t-ca7f73574a3295c3dc1d7d0dadc4b1a83dc01c3a94c55cea94f7abcde221100b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>Angiotensin-Converting Enzyme Inhibitors</topic><topic>Animals</topic><topic>Antihypertensive Agents - chemical synthesis</topic><topic>Dipeptides - chemical synthesis</topic><topic>Dipeptides - metabolism</topic><topic>Dipeptides - pharmacology</topic><topic>Hypertension, Renovascular - drug therapy</topic><topic>Rats</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Almquist, Ronald G</creatorcontrib><creatorcontrib>Chao, Wan Ru</creatorcontrib><creatorcontrib>Jennings-White, Clive</creatorcontrib><collection>Istex</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>Almquist, Ronald G</au><au>Chao, Wan Ru</au><au>Jennings-White, Clive</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and biological activity of carboxylic acid replacement analogs of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1985-08</date><risdate>1985</risdate><volume>28</volume><issue>8</issue><spage>1067</spage><epage>1071</epage><pages>1067-1071</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>The carboxylic acid group on the proline of 1 was replaced by a phosphoric acid, a hydroxamic acid, and a tetrazole to give compounds 2-4, respectively. Testing of 2-4 as angiotensin converting enzyme (ACE) inhibitors gave I50 values of 100, 1.6, and 22 microM, respectively, compared to 0.07 microM for 1. A hydroxamic acid derivative of the ketomethylene pentapeptide analogue 18 was then synthesized. This compound, 17, had an ACE I50 of 0.011 microM compared to 0.0076 microM for 18. Oral administration of 10 mg/kg of 17 to renal hypertensive rats had no effect on blood pressure or heart rate.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>2991518</pmid><doi>10.1021/jm00146a015</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 1985-08, Vol.28 (8), p.1067-1071 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_76225552 |
| source | MEDLINE; ACS Publications |
| subjects | Angiotensin-Converting Enzyme Inhibitors Animals Antihypertensive Agents - chemical synthesis Dipeptides - chemical synthesis Dipeptides - metabolism Dipeptides - pharmacology Hypertension, Renovascular - drug therapy Rats Structure-Activity Relationship |
| title | Synthesis and biological activity of carboxylic acid replacement analogs of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline |
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