Synthesis and antihypertensive activity of a series of 4-amino-6,7-dimethoxyquinazoline derivatives
A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential alpha 1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethane...
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| Veröffentlicht in: | Journal of medicinal chemistry 1986-01, Vol.29 (1), p.19-25 |
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| container_title | Journal of medicinal chemistry |
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| creator | Manoury, Philippe M Binet, Jean L Dumas, Andre P Lefevre-Borg, Francoise Cavero, Icilio |
| description | A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential alpha 1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives, albeit being structurally more closely related to prazosin, were devoid of this property. The most active derivative, N-[3-[(4-amino-6, 7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furancarbo xamide hydrochloride, alfuzosin (12), showed high selectivity for peripheral alpha 1-postjunctional adrenoceptors. At equiactive antihypertensive doses, its effect on the pressor response to postural changes in conscious dog was less marked than that shown by prazosin. In the light of these results, alfuzosin was selected for clinical evaluation. |
| doi_str_mv | 10.1021/jm00151a003 |
| format | Article |
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When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives, albeit being structurally more closely related to prazosin, were devoid of this property. The most active derivative, N-[3-[(4-amino-6, 7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furancarbo xamide hydrochloride, alfuzosin (12), showed high selectivity for peripheral alpha 1-postjunctional adrenoceptors. At equiactive antihypertensive doses, its effect on the pressor response to postural changes in conscious dog was less marked than that shown by prazosin. 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Med. Chem</addtitle><description>A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential alpha 1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives, albeit being structurally more closely related to prazosin, were devoid of this property. The most active derivative, N-[3-[(4-amino-6, 7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furancarbo xamide hydrochloride, alfuzosin (12), showed high selectivity for peripheral alpha 1-postjunctional adrenoceptors. At equiactive antihypertensive doses, its effect on the pressor response to postural changes in conscious dog was less marked than that shown by prazosin. In the light of these results, alfuzosin was selected for clinical evaluation.</description><subject>Animals</subject><subject>Chemical Phenomena</subject><subject>Chemistry</subject><subject>Exact sciences and technology</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>Hypertension - drug therapy</subject><subject>Male</subject><subject>Organic chemistry</subject><subject>Preparations and properties</subject><subject>Quinazolines - chemical synthesis</subject><subject>Quinazolines - therapeutic use</subject><subject>Rats</subject><subject>Rats, Inbred SHR</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>eNpt0M1r2zAYBnAxNrqs3WnngQ9jO2zu9GFZ0rGUtR0NWyHdWbyWZKLMllPJDvX--qokhB16EBI8P728PAh9IPicYEq-b3qMCSeAMXuFFoRTXFYSV6_RAmNKS1pT9ha9S2mDsyCUnaATpipSEbxAZjWHce2STwUEm8_o1_PWxdGF5HeuADP6nR_nYmgLKJKL3qXnd1VC78NQ1t9EaX3vxvXwOD9MPsC_ofPBFTbTHeTPLp2hNy10yb0_3Kfoz9WP-8ubcvn7-uflxbIEJtlY1k3LFG4EV1waYYmzgA1uoCFcWgzUUseF5EoaBaqiVlraCNqqFgRwySk7RZ_3c7dxeJhcGnXvk3FdB8ENU9KiroViSmb4dQ9NHFKKrtXb6HuIsyZYP1eq_6s064-HsVPTO3u0hw5z_umQQzLQtRGC8enIJCeVUDyzcs98Gt3jMYb4V9eCCa7v71b6ZvXrii9Xt_ou-y97DybpzTDFkLt7ccEnQ7aarw</recordid><startdate>19860101</startdate><enddate>19860101</enddate><creator>Manoury, Philippe M</creator><creator>Binet, Jean L</creator><creator>Dumas, Andre P</creator><creator>Lefevre-Borg, Francoise</creator><creator>Cavero, Icilio</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>19860101</creationdate><title>Synthesis and antihypertensive activity of a series of 4-amino-6,7-dimethoxyquinazoline derivatives</title><author>Manoury, Philippe M ; Binet, Jean L ; Dumas, Andre P ; Lefevre-Borg, Francoise ; Cavero, Icilio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a383t-6bf390b75958c7d1eda0c0bab158d0a2d2e578598c9a942d8d2b72f9fa7a58523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1986</creationdate><topic>Animals</topic><topic>Chemical Phenomena</topic><topic>Chemistry</topic><topic>Exact sciences and technology</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>Hypertension - drug therapy</topic><topic>Male</topic><topic>Organic chemistry</topic><topic>Preparations and properties</topic><topic>Quinazolines - chemical synthesis</topic><topic>Quinazolines - therapeutic use</topic><topic>Rats</topic><topic>Rats, Inbred SHR</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Manoury, Philippe M</creatorcontrib><creatorcontrib>Binet, Jean L</creatorcontrib><creatorcontrib>Dumas, Andre P</creatorcontrib><creatorcontrib>Lefevre-Borg, Francoise</creatorcontrib><creatorcontrib>Cavero, Icilio</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>Manoury, Philippe M</au><au>Binet, Jean L</au><au>Dumas, Andre P</au><au>Lefevre-Borg, Francoise</au><au>Cavero, Icilio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and antihypertensive activity of a series of 4-amino-6,7-dimethoxyquinazoline derivatives</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1986-01-01</date><risdate>1986</risdate><volume>29</volume><issue>1</issue><spage>19</spage><epage>25</epage><pages>19-25</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential alpha 1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives, albeit being structurally more closely related to prazosin, were devoid of this property. The most active derivative, N-[3-[(4-amino-6, 7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furancarbo xamide hydrochloride, alfuzosin (12), showed high selectivity for peripheral alpha 1-postjunctional adrenoceptors. 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| subjects | Animals Chemical Phenomena Chemistry Exact sciences and technology Heterocyclic compounds Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings Hypertension - drug therapy Male Organic chemistry Preparations and properties Quinazolines - chemical synthesis Quinazolines - therapeutic use Rats Rats, Inbred SHR Structure-Activity Relationship |
| title | Synthesis and antihypertensive activity of a series of 4-amino-6,7-dimethoxyquinazoline derivatives |
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