Substituted tetrahydroquinolines as potent allosteric inhibitors of reverse transcriptase and its key mutants
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are key elements of multidrug regimens, called HAART (Highly Active Antiretroviral Therapy), that are used to treat HIV-1 infections. Elucidation of the structure–activity relationships of the thiocarbamate moiety of the previous published lea...
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| creator | Su, Dai-Shi Lim, John J. Tinney, Elizabeth Wan, Bang-Lin Young, Mary Beth Anderson, Kenneth D. Rudd, Deanne Munshi, Vandna Bahnck, Carolyn Felock, Peter J. Lu, Meiqing Lai, Ming-Tain Touch, Sinoeun Moyer, Gregory DiStefano, Daniel J. Flynn, Jessica A. Liang, Yuexia Sanchez, Rosa Prasad, Sridhar Yan, Youwei Perlow-Poehnelt, Rebecca Torrent, Maricel Miller, Mike Vacca, Joe P. Williams, Theresa M. Anthony, Neville J. |
| description | Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are key elements of multidrug regimens, called HAART (Highly Active Antiretroviral Therapy), that are used to treat HIV-1 infections. Elucidation of the structure–activity relationships of the thiocarbamate moiety of the previous published lead compound
2 provided a series of novel tetrahydroquinoline derivatives as potent inhibitors of HIV-1 RT with nanomolar intrinsic activity on the WT and key mutant enzymes and potent antiviral activity in infected cells. The SAR optimization, mutation profiles, preparation of compounds, and pharmacokinetic profile of compounds are described. |
| doi_str_mv | 10.1016/j.bmcl.2009.07.031 |
| format | Article |
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Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Crystal structure</subject><subject>Crystallography, X-Ray</subject><subject>ENZYME INHIBITORS</subject><subject>GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE</subject><subject>HIV Reverse Transcriptase - antagonists & inhibitors</subject><subject>HIV Reverse Transcriptase - metabolism</subject><subject>Human immunodeficiency virus 1</subject><subject>Medical sciences</subject><subject>Molecular Conformation</subject><subject>Molecular modeling</subject><subject>Mutant Proteins - antagonists & inhibitors</subject><subject>Mutant Proteins - metabolism</subject><subject>Mutant virus</subject><subject>MUTANTS</subject><subject>MUTATIONS</subject><subject>Non-nucleoside reverse transcriptase inhibitor (NNRTI)</subject><subject>PHARMACOLOGY</subject><subject>Pharmacology. Drug treatments</subject><subject>QUINOLINES</subject><subject>Quinolines - chemical synthesis</subject><subject>Quinolines - chemistry</subject><subject>Quinolines - pharmacology</subject><subject>Reverse Transcriptase Inhibitors - chemical synthesis</subject><subject>Reverse Transcriptase Inhibitors - chemistry</subject><subject>Reverse Transcriptase Inhibitors - pharmacology</subject><subject>SAR</subject><subject>Structure-Activity Relationship</subject><subject>STRUCTURE-ACTIVITY RELATIONSHIPS</subject><subject>SYNTHESIS</subject><subject>Tetrahydroquinoline</subject><subject>THERAPY</subject><subject>Thiocarbamates - chemistry</subject><subject>Thiocarbamates - pharmacology</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU-LFDEQxYMo7uzoF_AgQXA99Zh0ku4O7EUW_8GCBxW8hXS6msnYnYyp9MJ8e9PMoLc9FQW_V1WvHiGvONtxxpv3h10_u2lXM6Z3rN0xwZ-QDZeNrIRk6inZMN2wqtPy1xW5RjwwxiWT8jm54roRXNXdhszflx6zz0uGgWbIye5PQ4p_Fh_i5AMgtUiPMUPI1E5TxAzJO-rD3vc-x4Q0jjTBAyQEWtQBXfLHbEtnw0B9RvobTnResg0ZX5Bno50QXl7qlvz89PHH3Zfq_tvnr3cf7isnpciVVV2v-ajZOKq2VyNoGKUatJK1baRgYBvQqhe6ByFbJ8Ba3dXAOfQd07UWW_LmPLfc6w06n8HtXQwBXDacsYartkDvztBx9QuYzezRwTTZAHFB0wqhm1aXhVty8yhZcy5q3vIC1mfQpYiYYDTH5GebTmWpWTMzB7NmZtbMDGtNyayIXl-mL_0Mw3_JJaQCvL0AFp2dxvJl5_EfV_NO6bZVhbs9c1Be--Ahrc4hOBh8Wo0P0T92x1-6DLdc</recordid><startdate>20090901</startdate><enddate>20090901</enddate><creator>Su, Dai-Shi</creator><creator>Lim, John J.</creator><creator>Tinney, Elizabeth</creator><creator>Wan, Bang-Lin</creator><creator>Young, Mary Beth</creator><creator>Anderson, Kenneth D.</creator><creator>Rudd, Deanne</creator><creator>Munshi, Vandna</creator><creator>Bahnck, Carolyn</creator><creator>Felock, Peter J.</creator><creator>Lu, Meiqing</creator><creator>Lai, Ming-Tain</creator><creator>Touch, Sinoeun</creator><creator>Moyer, Gregory</creator><creator>DiStefano, Daniel J.</creator><creator>Flynn, Jessica A.</creator><creator>Liang, Yuexia</creator><creator>Sanchez, Rosa</creator><creator>Prasad, Sridhar</creator><creator>Yan, Youwei</creator><creator>Perlow-Poehnelt, Rebecca</creator><creator>Torrent, Maricel</creator><creator>Miller, Mike</creator><creator>Vacca, Joe P.</creator><creator>Williams, Theresa M.</creator><creator>Anthony, Neville J.</creator><general>Elsevier Ltd</general><general>Elsevier</general><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>7QO</scope><scope>7T7</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20090901</creationdate><title>Substituted tetrahydroquinolines as potent allosteric inhibitors of reverse transcriptase and its key mutants</title><author>Su, Dai-Shi ; Lim, John J. ; Tinney, Elizabeth ; Wan, Bang-Lin ; Young, Mary Beth ; Anderson, Kenneth D. ; Rudd, Deanne ; Munshi, Vandna ; Bahnck, Carolyn ; Felock, Peter J. ; Lu, Meiqing ; Lai, Ming-Tain ; Touch, Sinoeun ; Moyer, Gregory ; DiStefano, Daniel J. ; Flynn, Jessica A. ; Liang, Yuexia ; Sanchez, Rosa ; Prasad, Sridhar ; Yan, Youwei ; Perlow-Poehnelt, Rebecca ; Torrent, Maricel ; Miller, Mike ; Vacca, Joe P. ; Williams, Theresa M. ; Anthony, Neville J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-a58b91f90ff57b5fe9ef45d9542a6430ea6e95b39be347c3eaa982e11eb809293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>AIDS VIRUS</topic><topic>Allosteric Site</topic><topic>Anti-HIV Agents - chemical synthesis</topic><topic>Anti-HIV Agents - chemistry</topic><topic>Anti-HIV Agents - pharmacology</topic><topic>Antibiotics. 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Drug treatments</topic><topic>QUINOLINES</topic><topic>Quinolines - chemical synthesis</topic><topic>Quinolines - chemistry</topic><topic>Quinolines - pharmacology</topic><topic>Reverse Transcriptase Inhibitors - chemical synthesis</topic><topic>Reverse Transcriptase Inhibitors - chemistry</topic><topic>Reverse Transcriptase Inhibitors - pharmacology</topic><topic>SAR</topic><topic>Structure-Activity Relationship</topic><topic>STRUCTURE-ACTIVITY RELATIONSHIPS</topic><topic>SYNTHESIS</topic><topic>Tetrahydroquinoline</topic><topic>THERAPY</topic><topic>Thiocarbamates - chemistry</topic><topic>Thiocarbamates - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Su, Dai-Shi</creatorcontrib><creatorcontrib>Lim, John J.</creatorcontrib><creatorcontrib>Tinney, Elizabeth</creatorcontrib><creatorcontrib>Wan, Bang-Lin</creatorcontrib><creatorcontrib>Young, Mary Beth</creatorcontrib><creatorcontrib>Anderson, Kenneth D.</creatorcontrib><creatorcontrib>Rudd, Deanne</creatorcontrib><creatorcontrib>Munshi, Vandna</creatorcontrib><creatorcontrib>Bahnck, Carolyn</creatorcontrib><creatorcontrib>Felock, Peter J.</creatorcontrib><creatorcontrib>Lu, Meiqing</creatorcontrib><creatorcontrib>Lai, Ming-Tain</creatorcontrib><creatorcontrib>Touch, Sinoeun</creatorcontrib><creatorcontrib>Moyer, Gregory</creatorcontrib><creatorcontrib>DiStefano, Daniel J.</creatorcontrib><creatorcontrib>Flynn, Jessica A.</creatorcontrib><creatorcontrib>Liang, Yuexia</creatorcontrib><creatorcontrib>Sanchez, Rosa</creatorcontrib><creatorcontrib>Prasad, Sridhar</creatorcontrib><creatorcontrib>Yan, Youwei</creatorcontrib><creatorcontrib>Perlow-Poehnelt, Rebecca</creatorcontrib><creatorcontrib>Torrent, Maricel</creatorcontrib><creatorcontrib>Miller, Mike</creatorcontrib><creatorcontrib>Vacca, Joe P.</creatorcontrib><creatorcontrib>Williams, Theresa M.</creatorcontrib><creatorcontrib>Anthony, Neville J.</creatorcontrib><creatorcontrib>Argonne National Lab. 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| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2009-09, Vol.19 (17), p.5119-5123 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_osti_scitechconnect_1006157 |
| source | MEDLINE; Elsevier ScienceDirect Journals Collection |
| subjects | AIDS VIRUS Allosteric Site Anti-HIV Agents - chemical synthesis Anti-HIV Agents - chemistry Anti-HIV Agents - pharmacology Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents BASIC BIOLOGICAL SCIENCES Binding Sites Biological and medical sciences Crystal structure Crystallography, X-Ray ENZYME INHIBITORS GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE HIV Reverse Transcriptase - antagonists & inhibitors HIV Reverse Transcriptase - metabolism Human immunodeficiency virus 1 Medical sciences Molecular Conformation Molecular modeling Mutant Proteins - antagonists & inhibitors Mutant Proteins - metabolism Mutant virus MUTANTS MUTATIONS Non-nucleoside reverse transcriptase inhibitor (NNRTI) PHARMACOLOGY Pharmacology. Drug treatments QUINOLINES Quinolines - chemical synthesis Quinolines - chemistry Quinolines - pharmacology Reverse Transcriptase Inhibitors - chemical synthesis Reverse Transcriptase Inhibitors - chemistry Reverse Transcriptase Inhibitors - pharmacology SAR Structure-Activity Relationship STRUCTURE-ACTIVITY RELATIONSHIPS SYNTHESIS Tetrahydroquinoline THERAPY Thiocarbamates - chemistry Thiocarbamates - pharmacology |
| title | Substituted tetrahydroquinolines as potent allosteric inhibitors of reverse transcriptase and its key mutants |
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