Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains
Novel diarylpyrimidines (DAPY), which represent next generation of non-nucleoside reverse transcriptase inhibitors (NNRTIs), were synthesized and their activities against human immunodeficiency virus type I (HIV-1) assessed. Modulations at positions 2 and 6 of the left phenyl ring generated interest...
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| Veröffentlicht in: | European journal of medicinal chemistry 2007-05, Vol.42 (5), p.567-579 |
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| container_title | European journal of medicinal chemistry |
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| creator | Mordant, Céline Schmitt, Benoit Pasquier, Elisabeth Demestre, Christophe Queguiner, Laurence Masungi, Chantal Peeters, Anik Smeulders, Liesbeth Bettens, Eva Hertogs, Kurt Heeres, Jan Lewi, Paul Guillemont, Jerome |
| description | Novel diarylpyrimidines (DAPY), which represent next generation of non-nucleoside reverse transcriptase inhibitors (NNRTIs), were synthesized and their activities against human immunodeficiency virus type I (HIV-1) assessed. Modulations at positions 2 and 6 of the left phenyl ring generated interesting derivatives of TMC278 displaying high potency against wild-type and mutant viruses compared to nevirapine and efavirenz. The pharmacokinetic profile of the best newly synthesized DAPY was evaluated and compared with TMC278 now in phase II clinical trials.
[Display omitted] Design and synthesis of TMC278 analogues by modulation on the left wing of the diarylpyrimidine (DAPY) were investigated. |
| doi_str_mv | 10.1016/j.ejmech.2006.11.014 |
| format | Article |
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[Display omitted] Design and synthesis of TMC278 analogues by modulation on the left wing of the diarylpyrimidine (DAPY) were investigated.</description><identifier>ISSN: 0223-5234</identifier><identifier>EISSN: 1768-3254</identifier><identifier>DOI: 10.1016/j.ejmech.2006.11.014</identifier><identifier>PMID: 17223230</identifier><identifier>CODEN: EJMCA5</identifier><language>eng</language><publisher>Oxford: Elsevier Masson SAS</publisher><subject>Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Biological and medical sciences ; Chromatography, High Pressure Liquid ; Diarylpyrimidine (DAPY) ; Dogs ; Female ; HIV-1 ; HIV-1 - drug effects ; Magnetic Resonance Spectroscopy ; Male ; Mass Spectrometry ; Medical sciences ; Nitriles - chemical synthesis ; Nitriles - pharmacology ; NNRTI ; Pharmacology. Drug treatments ; Pyrimidines - chemical synthesis ; Pyrimidines - chemistry ; Pyrimidines - pharmacology ; Rats ; Rats, Wistar ; Reverse Transcriptase Inhibitors - chemical synthesis ; Reverse Transcriptase Inhibitors - pharmacology ; Rilpivirine ; Spectrophotometry, Ultraviolet</subject><ispartof>European journal of medicinal chemistry, 2007-05, Vol.42 (5), p.567-579</ispartof><rights>2006 Elsevier Masson SAS</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-9d0ccff3763ceb115ec441c286affd720c2349617826e21b174e71f3dd81f3893</citedby><cites>FETCH-LOGICAL-c390t-9d0ccff3763ceb115ec441c286affd720c2349617826e21b174e71f3dd81f3893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejmech.2006.11.014$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18767292$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17223230$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mordant, Céline</creatorcontrib><creatorcontrib>Schmitt, Benoit</creatorcontrib><creatorcontrib>Pasquier, Elisabeth</creatorcontrib><creatorcontrib>Demestre, Christophe</creatorcontrib><creatorcontrib>Queguiner, Laurence</creatorcontrib><creatorcontrib>Masungi, Chantal</creatorcontrib><creatorcontrib>Peeters, Anik</creatorcontrib><creatorcontrib>Smeulders, Liesbeth</creatorcontrib><creatorcontrib>Bettens, Eva</creatorcontrib><creatorcontrib>Hertogs, Kurt</creatorcontrib><creatorcontrib>Heeres, Jan</creatorcontrib><creatorcontrib>Lewi, Paul</creatorcontrib><creatorcontrib>Guillemont, Jerome</creatorcontrib><title>Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains</title><title>European journal of medicinal chemistry</title><addtitle>Eur J Med Chem</addtitle><description>Novel diarylpyrimidines (DAPY), which represent next generation of non-nucleoside reverse transcriptase inhibitors (NNRTIs), were synthesized and their activities against human immunodeficiency virus type I (HIV-1) assessed. Modulations at positions 2 and 6 of the left phenyl ring generated interesting derivatives of TMC278 displaying high potency against wild-type and mutant viruses compared to nevirapine and efavirenz. The pharmacokinetic profile of the best newly synthesized DAPY was evaluated and compared with TMC278 now in phase II clinical trials.
[Display omitted] Design and synthesis of TMC278 analogues by modulation on the left wing of the diarylpyrimidine (DAPY) were investigated.</description><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Diarylpyrimidine (DAPY)</subject><subject>Dogs</subject><subject>Female</subject><subject>HIV-1</subject><subject>HIV-1 - drug effects</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Nitriles - chemical synthesis</subject><subject>Nitriles - pharmacology</subject><subject>NNRTI</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyrimidines - chemical synthesis</subject><subject>Pyrimidines - chemistry</subject><subject>Pyrimidines - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Reverse Transcriptase Inhibitors - chemical synthesis</subject><subject>Reverse Transcriptase Inhibitors - pharmacology</subject><subject>Rilpivirine</subject><subject>Spectrophotometry, Ultraviolet</subject><issn>0223-5234</issn><issn>1768-3254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFu1DAQhi0EokvhDRDyBW4JHjuJkwsSWhVaqYgDhavltcetV06y2N5FOfHqeLsr9cbFHtnfP5r5CHkLrAYG3cdtjdsRzUPNGetqgJpB84ysQHZ9JXjbPCcrxrmoWi6aC_IqpS1jrO0Ye0kuQJYfLtiK_P2xTPkBk090dnSaDxio9TouYbdEP3rrJ6R60mG-3-Mjc_dtzWVf3iwtQR9Llf3BRx2oNscqL1Tfaz-lTK9vflVA__hgq7zs8DE07nNJ0JTjkXlNXjgdEr4535fk55eru_V1dfv96836821lxMByNVhmjHNCdsLgBqBF0zRgeN9p56zkzJQthw5kzzvksAHZoAQnrO3L2Q_iknw49d3F-XfZJKvRJ4Mh6AnnfVKStSAaIQvYnEAT55QiOrUrHooQBUwdxautOolXR_EKQBXxJfbu3H-_GdE-hc6mC_D-DOhkdHBRT8anJ66XneQDL9ynE4fFxsFjVMl4nAxaH9FkZWf__0n-AREvo9s</recordid><startdate>20070501</startdate><enddate>20070501</enddate><creator>Mordant, Céline</creator><creator>Schmitt, Benoit</creator><creator>Pasquier, Elisabeth</creator><creator>Demestre, Christophe</creator><creator>Queguiner, Laurence</creator><creator>Masungi, Chantal</creator><creator>Peeters, Anik</creator><creator>Smeulders, Liesbeth</creator><creator>Bettens, Eva</creator><creator>Hertogs, Kurt</creator><creator>Heeres, Jan</creator><creator>Lewi, Paul</creator><creator>Guillemont, Jerome</creator><general>Elsevier Masson SAS</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>7X8</scope></search><sort><creationdate>20070501</creationdate><title>Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains</title><author>Mordant, Céline ; Schmitt, Benoit ; Pasquier, Elisabeth ; Demestre, Christophe ; Queguiner, Laurence ; Masungi, Chantal ; Peeters, Anik ; Smeulders, Liesbeth ; Bettens, Eva ; Hertogs, Kurt ; Heeres, Jan ; Lewi, Paul ; Guillemont, Jerome</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-9d0ccff3763ceb115ec441c286affd720c2349617826e21b174e71f3dd81f3893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Diarylpyrimidine (DAPY)</topic><topic>Dogs</topic><topic>Female</topic><topic>HIV-1</topic><topic>HIV-1 - drug effects</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Nitriles - chemical synthesis</topic><topic>Nitriles - pharmacology</topic><topic>NNRTI</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyrimidines - chemical synthesis</topic><topic>Pyrimidines - chemistry</topic><topic>Pyrimidines - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Reverse Transcriptase Inhibitors - chemical synthesis</topic><topic>Reverse Transcriptase Inhibitors - pharmacology</topic><topic>Rilpivirine</topic><topic>Spectrophotometry, Ultraviolet</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mordant, Céline</creatorcontrib><creatorcontrib>Schmitt, Benoit</creatorcontrib><creatorcontrib>Pasquier, Elisabeth</creatorcontrib><creatorcontrib>Demestre, Christophe</creatorcontrib><creatorcontrib>Queguiner, Laurence</creatorcontrib><creatorcontrib>Masungi, Chantal</creatorcontrib><creatorcontrib>Peeters, Anik</creatorcontrib><creatorcontrib>Smeulders, Liesbeth</creatorcontrib><creatorcontrib>Bettens, Eva</creatorcontrib><creatorcontrib>Hertogs, Kurt</creatorcontrib><creatorcontrib>Heeres, Jan</creatorcontrib><creatorcontrib>Lewi, Paul</creatorcontrib><creatorcontrib>Guillemont, Jerome</creatorcontrib><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>European journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mordant, Céline</au><au>Schmitt, Benoit</au><au>Pasquier, Elisabeth</au><au>Demestre, Christophe</au><au>Queguiner, Laurence</au><au>Masungi, Chantal</au><au>Peeters, Anik</au><au>Smeulders, Liesbeth</au><au>Bettens, Eva</au><au>Hertogs, Kurt</au><au>Heeres, Jan</au><au>Lewi, Paul</au><au>Guillemont, Jerome</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains</atitle><jtitle>European journal of medicinal chemistry</jtitle><addtitle>Eur J Med Chem</addtitle><date>2007-05-01</date><risdate>2007</risdate><volume>42</volume><issue>5</issue><spage>567</spage><epage>579</epage><pages>567-579</pages><issn>0223-5234</issn><eissn>1768-3254</eissn><coden>EJMCA5</coden><abstract>Novel diarylpyrimidines (DAPY), which represent next generation of non-nucleoside reverse transcriptase inhibitors (NNRTIs), were synthesized and their activities against human immunodeficiency virus type I (HIV-1) assessed. Modulations at positions 2 and 6 of the left phenyl ring generated interesting derivatives of TMC278 displaying high potency against wild-type and mutant viruses compared to nevirapine and efavirenz. The pharmacokinetic profile of the best newly synthesized DAPY was evaluated and compared with TMC278 now in phase II clinical trials.
[Display omitted] Design and synthesis of TMC278 analogues by modulation on the left wing of the diarylpyrimidine (DAPY) were investigated.</abstract><cop>Oxford</cop><pub>Elsevier Masson SAS</pub><pmid>17223230</pmid><doi>10.1016/j.ejmech.2006.11.014</doi><tpages>13</tpages></addata></record> |
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| subjects | Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences Chromatography, High Pressure Liquid Diarylpyrimidine (DAPY) Dogs Female HIV-1 HIV-1 - drug effects Magnetic Resonance Spectroscopy Male Mass Spectrometry Medical sciences Nitriles - chemical synthesis Nitriles - pharmacology NNRTI Pharmacology. Drug treatments Pyrimidines - chemical synthesis Pyrimidines - chemistry Pyrimidines - pharmacology Rats Rats, Wistar Reverse Transcriptase Inhibitors - chemical synthesis Reverse Transcriptase Inhibitors - pharmacology Rilpivirine Spectrophotometry, Ultraviolet |
| title | Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains |
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