Design and synthesis of new tetrahydroquinolines derivatives as CETP inhibitors
This letter describes the discovery and SAR optimization of tetrazoyl tetrahydroquinoline derivatives as potent CETP inhibitors. Compound 6m exhibited robust HDL-c increase in hCETP/hApoA1 double transgenic model and favorable pharmacokinetic properties.
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2012-06, Vol.22 (11), p.3671-3675 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Escribano, Ana Mateo, Ana I. Martin de la Nava, Eva M. Mayhugh, Daniel R. Cockerham, Sandra L. Beyer, Thomas P. Schmidt, Robert J. Cao, Guoqing Zhang, Youyan Jones, Timothy M. Borel, Anthony G. Sweetana, Stephanie A. Cannady, Ellen A. Mantlo, Nathan B. |
| description | This letter describes the discovery and SAR optimization of tetrazoyl tetrahydroquinoline derivatives as potent CETP inhibitors. Compound 6m exhibited robust HDL-c increase in hCETP/hApoA1 double transgenic model and favorable pharmacokinetic properties. |
| doi_str_mv | 10.1016/j.bmcl.2012.04.042 |
| format | Article |
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Compound 6m exhibited robust HDL-c increase in hCETP/hApoA1 double transgenic model and favorable pharmacokinetic properties.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2012.04.042</identifier><identifier>PMID: 22543028</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Animals ; Apolipoprotein A-I - genetics ; Apolipoprotein A-I - metabolism ; Biological and medical sciences ; CETP inhibitor ; chemistry ; Cholesterol Ester Transfer Proteins - antagonists & inhibitors ; Cholesterol Ester Transfer Proteins - genetics ; Cholesterol Ester Transfer Proteins - metabolism ; Cholesterol, HDL - drug effects ; Cholesterol, HDL - metabolism ; Dogs ; Drug Design ; Female ; genetically modified organisms ; HDL-c ; Hypolipidemic Agents - chemical synthesis ; Hypolipidemic Agents - chemistry ; Hypolipidemic Agents - pharmacokinetics ; Injections, Intravenous ; Male ; Medical sciences ; Mice ; Mice, Transgenic ; Pharmacokinetics ; Pharmacology. Drug treatments ; Quinolines - chemical synthesis ; Quinolines - chemistry ; Quinolines - pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Structure-Activity Relationship ; Tetrahydroquinolines ; Tetrazoles - chemical synthesis ; Tetrazoles - chemistry ; Tetrazoles - pharmacokinetics</subject><ispartof>Bioorganic & medicinal chemistry letters, 2012-06, Vol.22 (11), p.3671-3675</ispartof><rights>2012 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Ltd. 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Compound 6m exhibited robust HDL-c increase in hCETP/hApoA1 double transgenic model and favorable pharmacokinetic properties.</description><subject>Animals</subject><subject>Apolipoprotein A-I - genetics</subject><subject>Apolipoprotein A-I - metabolism</subject><subject>Biological and medical sciences</subject><subject>CETP inhibitor</subject><subject>chemistry</subject><subject>Cholesterol Ester Transfer Proteins - antagonists & inhibitors</subject><subject>Cholesterol Ester Transfer Proteins - genetics</subject><subject>Cholesterol Ester Transfer Proteins - metabolism</subject><subject>Cholesterol, HDL - drug effects</subject><subject>Cholesterol, HDL - metabolism</subject><subject>Dogs</subject><subject>Drug Design</subject><subject>Female</subject><subject>genetically modified organisms</subject><subject>HDL-c</subject><subject>Hypolipidemic Agents - chemical synthesis</subject><subject>Hypolipidemic Agents - chemistry</subject><subject>Hypolipidemic Agents - pharmacokinetics</subject><subject>Injections, Intravenous</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Pharmacokinetics</subject><subject>Pharmacology. Drug treatments</subject><subject>Quinolines - chemical synthesis</subject><subject>Quinolines - chemistry</subject><subject>Quinolines - pharmacokinetics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Structure-Activity Relationship</subject><subject>Tetrahydroquinolines</subject><subject>Tetrazoles - chemical synthesis</subject><subject>Tetrazoles - chemistry</subject><subject>Tetrazoles - pharmacokinetics</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0d-LEzEQB_Agitc7_Qd80H0R7qV1ksxmN-CL1PMHHJxgBd9CNju5pmyzZ7Kt9L83pVXfRAgkgc9Mhm8Ye8FhwYGrN5tFt3XDQgAXC8CyxCM246hwLhHqx2wGWsG81fj9gl3mvAHgCIhP2YUQNUoQ7Yzdvacc7mNlY1_lQ5zW5Zqr0VeRflYTTcmuD30af-xCHIcQKVc9pbC3U9iXs83V8mb1pQpxHbowjSk_Y0-8HTI9P-9XbPXhZrX8NL-9-_h5-e527hDlNEfuG4sWuFSK20Z3BLXwdU-8ES2p2iP6xtfO60b4VlLnuaUOLPYdaK7lFbs-tX04zkZ5MtuQHQ2DjTTusuEgsQVdK_4flEtdMlSqUHGiLo05J_LmIYWtTYeCjk6ZjTlGbo6RG8CyRCl6ee6_67bU_yn5nXEBr8_AZmcHn2x0If91tUappSzu1cl5Oxp7n4r59rW8VJd_k6BaLOLtSVBJdh8omewCRUd9SOQm04_hX5P-AhepqB4</recordid><startdate>20120601</startdate><enddate>20120601</enddate><creator>Escribano, Ana</creator><creator>Mateo, Ana I.</creator><creator>Martin de la Nava, Eva M.</creator><creator>Mayhugh, Daniel R.</creator><creator>Cockerham, Sandra L.</creator><creator>Beyer, Thomas P.</creator><creator>Schmidt, Robert J.</creator><creator>Cao, Guoqing</creator><creator>Zhang, Youyan</creator><creator>Jones, Timothy M.</creator><creator>Borel, Anthony G.</creator><creator>Sweetana, Stephanie A.</creator><creator>Cannady, Ellen A.</creator><creator>Mantlo, Nathan B.</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>FBQ</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><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20120601</creationdate><title>Design and synthesis of new tetrahydroquinolines derivatives as CETP inhibitors</title><author>Escribano, Ana ; Mateo, Ana I. ; Martin de la Nava, Eva M. ; Mayhugh, Daniel R. ; Cockerham, Sandra L. ; Beyer, Thomas P. ; Schmidt, Robert J. ; Cao, Guoqing ; Zhang, Youyan ; Jones, Timothy M. ; Borel, Anthony G. ; Sweetana, Stephanie A. ; Cannady, Ellen A. ; Mantlo, Nathan B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-41f7a4a013661a79be052f5de1728e65f44f7f5cf972f83ebf1aeb0a4db09193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Apolipoprotein A-I - genetics</topic><topic>Apolipoprotein A-I - metabolism</topic><topic>Biological and medical sciences</topic><topic>CETP inhibitor</topic><topic>chemistry</topic><topic>Cholesterol Ester Transfer Proteins - antagonists & inhibitors</topic><topic>Cholesterol Ester Transfer Proteins - genetics</topic><topic>Cholesterol Ester Transfer Proteins - metabolism</topic><topic>Cholesterol, HDL - drug effects</topic><topic>Cholesterol, HDL - metabolism</topic><topic>Dogs</topic><topic>Drug Design</topic><topic>Female</topic><topic>genetically modified organisms</topic><topic>HDL-c</topic><topic>Hypolipidemic Agents - chemical synthesis</topic><topic>Hypolipidemic Agents - chemistry</topic><topic>Hypolipidemic Agents - pharmacokinetics</topic><topic>Injections, Intravenous</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Pharmacokinetics</topic><topic>Pharmacology. 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Compound 6m exhibited robust HDL-c increase in hCETP/hApoA1 double transgenic model and favorable pharmacokinetic properties.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>22543028</pmid><doi>10.1016/j.bmcl.2012.04.042</doi><tpages>5</tpages></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry letters, 2012-06, Vol.22 (11), p.3671-3675 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Apolipoprotein A-I - genetics Apolipoprotein A-I - metabolism Biological and medical sciences CETP inhibitor chemistry Cholesterol Ester Transfer Proteins - antagonists & inhibitors Cholesterol Ester Transfer Proteins - genetics Cholesterol Ester Transfer Proteins - metabolism Cholesterol, HDL - drug effects Cholesterol, HDL - metabolism Dogs Drug Design Female genetically modified organisms HDL-c Hypolipidemic Agents - chemical synthesis Hypolipidemic Agents - chemistry Hypolipidemic Agents - pharmacokinetics Injections, Intravenous Male Medical sciences Mice Mice, Transgenic Pharmacokinetics Pharmacology. Drug treatments Quinolines - chemical synthesis Quinolines - chemistry Quinolines - pharmacokinetics Rats Rats, Sprague-Dawley Structure-Activity Relationship Tetrahydroquinolines Tetrazoles - chemical synthesis Tetrazoles - chemistry Tetrazoles - pharmacokinetics |
| title | Design and synthesis of new tetrahydroquinolines derivatives as CETP inhibitors |
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