Specific targeting highly conserved residues in the HIV-1 reverse transcriptase primer grip region. design, synthesis, and biological evaluation of novel, potent, and broad spectrum NNRTIs with antiviral activity
Identifieur interne : 004D62 ( Main/Exploration ); précédent : 004D61; suivant : 004D63Specific targeting highly conserved residues in the HIV-1 reverse transcriptase primer grip region. design, synthesis, and biological evaluation of novel, potent, and broad spectrum NNRTIs with antiviral activity
Auteurs : Caterina Fattorusso [Italie] ; Sandra Gemma [Italie] ; Stefania Butini [Italie] ; Paul Huleatt [Italie] ; Bruno Catalanotti [Italie] ; Marco Persico [Italie] ; Meri De Angelis [Italie] ; Isabella Fiorini [Italie] ; V Ito Nacci [Italie] ; Anna Ramunno [Italie] ; Manuela Rodriquez [Italie] ; Giovanni Greco [Italie] ; Ettore Novellino [Italie] ; Alberto Bergamini [Italie] ; Stefano Marini [Italie] ; Massimo Coletta [Italie] ; Giovanni Maga [Italie] ; Silvio Spadari [Italie] ; Giuseppe Campiani [Italie]Source :
- Journal of medicinal chemistry : (Print) [ 0022-2623 ] ; 2005.
Descripteurs français
- KwdFr :
- Agents antiVIH (), Agents antiVIH (pharmacologie), Agents antiVIH (synthèse chimique), Animaux, Cellules cultivées, Conception de médicament, Humains, Inhibiteurs de la transcriptase inverse (), Inhibiteurs de la transcriptase inverse (pharmacologie), Inhibiteurs de la transcriptase inverse (synthèse chimique), Macrophages (), Macrophages (virologie), Modèles moléculaires, Mutation, Oxazépines (), Oxazépines (pharmacologie), Oxazépines (synthèse chimique), Pyrroles (), Pyrroles (pharmacologie), Pyrroles (synthèse chimique), Relation structure-activité, Réplication virale (), Résistance virale aux médicaments, Sites de fixation, Souris, Stéréoisomérie, Synergie des médicaments, Séquence conservée, Séquence d'acides aminés, Transcriptase inverse du VIH (), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (génétique), Zidovudine (pharmacologie).
- MESH :
- génétique : VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- pharmacologie : Agents antiVIH, Inhibiteurs de la transcriptase inverse, Oxazépines, Pyrroles, Zidovudine.
- synthèse chimique : Agents antiVIH, Inhibiteurs de la transcriptase inverse, Oxazépines, Pyrroles.
- virologie : Macrophages.
- Pascal (Inist)
- Agents antiVIH, Animaux, Cellules cultivées, Ciblage, Conception de médicament, Humains, Inhibiteurs de la transcriptase inverse, Macrophages, Modèles moléculaires, Mutation, Oxazépines, Pyrroles, Relation structure-activité, Réplication virale, Résistance virale aux médicaments, Sites de fixation, Souris, Stéréoisomérie, Synergie des médicaments, Séquence conservée, Séquence d'acides aminés, Transcriptase inverse du VIH, VIH-1 (Virus de l'Immunodéficience Humaine de type 1), Virus HIV1, RNA-directed DNA polymerase, Synthèse chimique, Relation structure activité, Inhibiteur reverse transcriptase, Composé non nucléoside, Antiviral, In vitro, Association médicamenteuse, Interaction médicamenteuse, Synergie, Zidovudine, Inhibiteur enzyme, Pyrrolobenzooxazépine, Pyrrolo[2,1-d][1,5]benzooxazépin-7-one(6-éthyl-6-[4-(phénoxyméthyl)phényl]), Lignée C8166.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Anti-HIV Agents (chemical synthesis), Anti-HIV Agents (chemistry), Anti-HIV Agents (pharmacology), Antiviral, Binding Sites, Cells, Cultured, Chemical synthesis, Conserved Sequence, Drug Design, Drug Resistance, Viral, Drug Synergism, Drug combination, Drug interaction, Enzyme inhibitor, HIV Reverse Transcriptase (chemistry), HIV-1 (drug effects), HIV-1 (genetics), HIV-1 virus, Humans, In vitro, Macrophages (drug effects), Macrophages (virology), Mice, Models, Molecular, Mutation, Non nucleoside compound, Oxazepines (chemical synthesis), Oxazepines (chemistry), Oxazepines (pharmacology), Pyrroles (chemical synthesis), Pyrroles (chemistry), Pyrroles (pharmacology), RNA-directed DNA polymerase, Reverse Transcriptase Inhibitors (chemical synthesis), Reverse Transcriptase Inhibitors (chemistry), Reverse Transcriptase Inhibitors (pharmacology), Reverse transcriptase inhibitor, Stereoisomerism, Structure activity relation, Structure-Activity Relationship, Synergism, Targeting, Virus Replication (drug effects), Zidovudine, Zidovudine (pharmacology).
- MESH :
- chemical , chemical synthesis : Anti-HIV Agents, Oxazepines, Pyrroles, Reverse Transcriptase Inhibitors.
- chemical , chemistry : Anti-HIV Agents, HIV Reverse Transcriptase, Oxazepines, Pyrroles, Reverse Transcriptase Inhibitors.
- chemical , pharmacology : Anti-HIV Agents, Oxazepines, Pyrroles, Reverse Transcriptase Inhibitors, Zidovudine.
- drug effects : HIV-1, Macrophages, Virus Replication.
- genetics : HIV-1.
- virology : Macrophages.
- Amino Acid Sequence, Animals, Binding Sites, Cells, Cultured, Conserved Sequence, Drug Design, Drug Resistance, Viral, Drug Synergism, Humans, Mice, Models, Molecular, Mutation, Stereoisomerism, Structure-Activity Relationship.
Abstract
Pyrrolobenzoxazepinones (PBOs) represent a new class of human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) whose prototype is 5. Molecular modeling studies based on the X-ray structures of HIV-1 RT prompted the synthesis of novel analogues which were tested as anti-HIV agents. The PBO derivatives specifically designed to target the highly conserved amino acid residues within the β12-β13 hairpin, namely primer grip, proved to be very potent against the most common mutant enzymes, including the highly resistant K103N mutant strain. Structure-activity relationships (SARs) are discussed in terms of a possible interaction with the RT binding site, depending on the nature of the substituents at C-6. Among the pyrrolobenzoxazepines investigated, 15c appeared to be the most promising NNRTI of the series characterized by potent antiviral activity, broad spectrum, and low cytotoxicity. 15c showed synergistic antiviral activity with AZT.
Affiliations:
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Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Huleatt, Paul" sort="Huleatt, Paul" uniqKey="Huleatt P" first="Paul" last="Huleatt">Paul Huleatt</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Catalanotti, Bruno" sort="Catalanotti, Bruno" uniqKey="Catalanotti B" first="Bruno" last="Catalanotti">Bruno Catalanotti</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Dipartimento di Sanita' Pubblica e Biologia Cellulare (DSP&BC), Universita' degli Studi di Roma "Tor Vergata", via Tor Vergata 135</s1><s2>00133 Roma</s2><s3>ITA</s3><sZ>5 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Persico, Marco" sort="Persico, Marco" uniqKey="Persico M" first="Marco" last="Persico">Marco Persico</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation></author><author><name sortKey="De Angelis, Meri" sort="De Angelis, Meri" uniqKey="De Angelis M" first="Meri" last="De Angelis">Meri De Angelis</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Fiorini, Isabella" sort="Fiorini, Isabella" uniqKey="Fiorini I" first="Isabella" last="Fiorini">Isabella Fiorini</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Nacci, V Ito" sort="Nacci, V Ito" uniqKey="Nacci V" first="V Ito" last="Nacci">V Ito Nacci</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Ramunno, Anna" sort="Ramunno, Anna" uniqKey="Ramunno A" first="Anna" last="Ramunno">Anna Ramunno</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Rodriquez, Manuela" sort="Rodriquez, Manuela" uniqKey="Rodriquez M" first="Manuela" last="Rodriquez">Manuela Rodriquez</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Greco, Giovanni" sort="Greco, Giovanni" uniqKey="Greco G" first="Giovanni" last="Greco">Giovanni Greco</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation></author><author><name sortKey="Novellino, Ettore" sort="Novellino, Ettore" uniqKey="Novellino E" first="Ettore" last="Novellino">Ettore Novellino</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation></author><author><name sortKey="Bergamini, Alberto" sort="Bergamini, Alberto" uniqKey="Bergamini A" first="Alberto" last="Bergamini">Alberto Bergamini</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Dipartimento di Medicina Sperimentale e Scienze Biochimiche (DMS&SB), Universita' degli Studi di Roma Tor Vergata, via Tor Vergata 135</s1><s2>00133 Roma</s2><s3>ITA</s3><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Marini, Stefano" sort="Marini, Stefano" uniqKey="Marini S" first="Stefano" last="Marini">Stefano Marini</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Dipartimento di Medicina Sperimentale e Scienze Biochimiche (DMS&SB), Universita' degli Studi di Roma Tor Vergata, via Tor Vergata 135</s1><s2>00133 Roma</s2><s3>ITA</s3><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Coletta, Massimo" sort="Coletta, Massimo" uniqKey="Coletta M" first="Massimo" last="Coletta">Massimo Coletta</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Dipartimento di Medicina Sperimentale e Scienze Biochimiche (DMS&SB), Universita' degli Studi di Roma Tor Vergata, via Tor Vergata 135</s1><s2>00133 Roma</s2><s3>ITA</s3><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Maga, Giovanni" sort="Maga, Giovanni" uniqKey="Maga G" first="Giovanni" last="Maga">Giovanni Maga</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Istituto di Genetica Molecolare (IGM) - CNR, via Abbiategrasso 207</s1><s2>27100 Pavia</s2><s3>ITA</s3><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>27100 Pavia</wicri:noRegion></affiliation></author><author><name sortKey="Spadari, Silvio" sort="Spadari, Silvio" uniqKey="Spadari S" first="Silvio" last="Spadari">Silvio Spadari</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Istituto di Genetica Molecolare (IGM) - CNR, via Abbiategrasso 207</s1><s2>27100 Pavia</s2><s3>ITA</s3><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>27100 Pavia</wicri:noRegion></affiliation></author><author><name sortKey="Campiani, Giuseppe" sort="Campiani, Giuseppe" uniqKey="Campiani G" first="Giuseppe" last="Campiani">Giuseppe Campiani</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">06-0200728</idno><date when="2005">2005</date><idno type="stanalyst">PASCAL 06-0200728 INIST</idno><idno type="RBID">Pascal:06-0200728</idno><idno type="wicri:Area/PascalFrancis/Corpus">000515</idno><idno type="wicri:Area/PascalFrancis/Curation">000475</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000571</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000571</idno><idno type="wicri:doubleKey">0022-2623:2005:Fattorusso C:specific:targeting:highly</idno><idno type="wicri:Area/Main/Merge">005091</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:16279773</idno><idno type="wicri:Area/PubMed/Corpus">002453</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002453</idno><idno type="wicri:Area/PubMed/Curation">002453</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002453</idno><idno type="wicri:Area/PubMed/Checkpoint">002472</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002472</idno><idno type="wicri:Area/Ncbi/Merge">001256</idno><idno type="wicri:Area/Ncbi/Curation">001256</idno><idno type="wicri:Area/Ncbi/Checkpoint">001256</idno><idno type="wicri:doubleKey">0022-2623:2005:Fattorusso C:specific:targeting:highly</idno><idno type="wicri:Area/Main/Merge">004877</idno><idno type="wicri:Area/Main/Curation">004D62</idno><idno type="wicri:Area/Main/Exploration">004D62</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Specific targeting highly conserved residues in the HIV-1 reverse transcriptase primer grip region. design, synthesis, and biological evaluation of novel, potent, and broad spectrum NNRTIs with antiviral activity</title><author><name sortKey="Fattorusso, Caterina" sort="Fattorusso, Caterina" uniqKey="Fattorusso C" first="Caterina" last="Fattorusso">Caterina Fattorusso</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation></author><author><name sortKey="Gemma, Sandra" sort="Gemma, Sandra" uniqKey="Gemma S" first="Sandra" last="Gemma">Sandra Gemma</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Butini, Stefania" sort="Butini, Stefania" uniqKey="Butini S" first="Stefania" last="Butini">Stefania Butini</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Huleatt, Paul" sort="Huleatt, Paul" uniqKey="Huleatt P" first="Paul" last="Huleatt">Paul Huleatt</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Catalanotti, Bruno" sort="Catalanotti, Bruno" uniqKey="Catalanotti B" first="Bruno" last="Catalanotti">Bruno Catalanotti</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Dipartimento di Sanita' Pubblica e Biologia Cellulare (DSP&BC), Universita' degli Studi di Roma "Tor Vergata", via Tor Vergata 135</s1><s2>00133 Roma</s2><s3>ITA</s3><sZ>5 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Persico, Marco" sort="Persico, Marco" uniqKey="Persico M" first="Marco" last="Persico">Marco Persico</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation></author><author><name sortKey="De Angelis, Meri" sort="De Angelis, Meri" uniqKey="De Angelis M" first="Meri" last="De Angelis">Meri De Angelis</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Fiorini, Isabella" sort="Fiorini, Isabella" uniqKey="Fiorini I" first="Isabella" last="Fiorini">Isabella Fiorini</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Nacci, V Ito" sort="Nacci, V Ito" uniqKey="Nacci V" first="V Ito" last="Nacci">V Ito Nacci</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Ramunno, Anna" sort="Ramunno, Anna" uniqKey="Ramunno A" first="Anna" last="Ramunno">Anna Ramunno</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Rodriquez, Manuela" sort="Rodriquez, Manuela" uniqKey="Rodriquez M" first="Manuela" last="Rodriquez">Manuela Rodriquez</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author><author><name sortKey="Greco, Giovanni" sort="Greco, Giovanni" uniqKey="Greco G" first="Giovanni" last="Greco">Giovanni Greco</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation></author><author><name sortKey="Novellino, Ettore" sort="Novellino, Ettore" uniqKey="Novellino E" first="Ettore" last="Novellino">Ettore Novellino</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation></author><author><name sortKey="Bergamini, Alberto" sort="Bergamini, Alberto" uniqKey="Bergamini A" first="Alberto" last="Bergamini">Alberto Bergamini</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Dipartimento di Medicina Sperimentale e Scienze Biochimiche (DMS&SB), Universita' degli Studi di Roma Tor Vergata, via Tor Vergata 135</s1><s2>00133 Roma</s2><s3>ITA</s3><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Marini, Stefano" sort="Marini, Stefano" uniqKey="Marini S" first="Stefano" last="Marini">Stefano Marini</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Dipartimento di Medicina Sperimentale e Scienze Biochimiche (DMS&SB), Universita' degli Studi di Roma Tor Vergata, via Tor Vergata 135</s1><s2>00133 Roma</s2><s3>ITA</s3><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Coletta, Massimo" sort="Coletta, Massimo" uniqKey="Coletta M" first="Massimo" last="Coletta">Massimo Coletta</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Dipartimento di Medicina Sperimentale e Scienze Biochimiche (DMS&SB), Universita' degli Studi di Roma Tor Vergata, via Tor Vergata 135</s1><s2>00133 Roma</s2><s3>ITA</s3><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Maga, Giovanni" sort="Maga, Giovanni" uniqKey="Maga G" first="Giovanni" last="Maga">Giovanni Maga</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Istituto di Genetica Molecolare (IGM) - CNR, via Abbiategrasso 207</s1><s2>27100 Pavia</s2><s3>ITA</s3><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>27100 Pavia</wicri:noRegion></affiliation></author><author><name sortKey="Spadari, Silvio" sort="Spadari, Silvio" uniqKey="Spadari S" first="Silvio" last="Spadari">Silvio Spadari</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Istituto di Genetica Molecolare (IGM) - CNR, via Abbiategrasso 207</s1><s2>27100 Pavia</s2><s3>ITA</s3><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>27100 Pavia</wicri:noRegion></affiliation></author><author><name sortKey="Campiani, Giuseppe" sort="Campiani, Giuseppe" uniqKey="Campiani G" first="Giuseppe" last="Campiani">Giuseppe Campiani</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Dipartimento Farmaco Chimico Tecnologico, via Aldo Moro, European Research Centre for Drug Discovery and Development, Universita' degli Studi di Siena</s1><s2>53100 Siena</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>53100 Siena</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Dipartimento di Chimica delle Sostanze Naturali e Dipartimento di Chimica Farmaceutica e Tossicologica, Universita' di Napoli "Federico II", via D. Montesano 49</s1><s2>80131 Napoli</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>80131 Napoli</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Journal of medicinal chemistry : (Print)</title><title level="j" type="abbreviated">J. med. chem. : (Print)</title><idno type="ISSN">0022-2623</idno><imprint><date when="2005">2005</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of medicinal chemistry : (Print)</title><title level="j" type="abbreviated">J. med. chem. : (Print)</title><idno type="ISSN">0022-2623</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Anti-HIV Agents (chemical synthesis)</term><term>Anti-HIV Agents (chemistry)</term><term>Anti-HIV Agents (pharmacology)</term><term>Antiviral</term><term>Binding Sites</term><term>Cells, Cultured</term><term>Chemical synthesis</term><term>Conserved Sequence</term><term>Drug Design</term><term>Drug Resistance, Viral</term><term>Drug Synergism</term><term>Drug combination</term><term>Drug interaction</term><term>Enzyme inhibitor</term><term>HIV Reverse Transcriptase (chemistry)</term><term>HIV-1 (drug effects)</term><term>HIV-1 (genetics)</term><term>HIV-1 virus</term><term>Humans</term><term>In vitro</term><term>Macrophages (drug effects)</term><term>Macrophages (virology)</term><term>Mice</term><term>Models, Molecular</term><term>Mutation</term><term>Non nucleoside compound</term><term>Oxazepines (chemical synthesis)</term><term>Oxazepines (chemistry)</term><term>Oxazepines (pharmacology)</term><term>Pyrroles (chemical synthesis)</term><term>Pyrroles (chemistry)</term><term>Pyrroles (pharmacology)</term><term>RNA-directed DNA polymerase</term><term>Reverse Transcriptase Inhibitors (chemical synthesis)</term><term>Reverse Transcriptase Inhibitors (chemistry)</term><term>Reverse Transcriptase Inhibitors (pharmacology)</term><term>Reverse transcriptase inhibitor</term><term>Stereoisomerism</term><term>Structure activity relation</term><term>Structure-Activity Relationship</term><term>Synergism</term><term>Targeting</term><term>Virus Replication (drug effects)</term><term>Zidovudine</term><term>Zidovudine (pharmacology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Agents antiVIH ()</term><term>Agents antiVIH (pharmacologie)</term><term>Agents antiVIH (synthèse chimique)</term><term>Animaux</term><term>Cellules cultivées</term><term>Conception de médicament</term><term>Humains</term><term>Inhibiteurs de la transcriptase inverse ()</term><term>Inhibiteurs de la transcriptase inverse (pharmacologie)</term><term>Inhibiteurs de la transcriptase inverse (synthèse chimique)</term><term>Macrophages ()</term><term>Macrophages (virologie)</term><term>Modèles moléculaires</term><term>Mutation</term><term>Oxazépines ()</term><term>Oxazépines (pharmacologie)</term><term>Oxazépines (synthèse chimique)</term><term>Pyrroles ()</term><term>Pyrroles (pharmacologie)</term><term>Pyrroles (synthèse chimique)</term><term>Relation structure-activité</term><term>Réplication virale ()</term><term>Résistance virale aux médicaments</term><term>Sites de fixation</term><term>Souris</term><term>Stéréoisomérie</term><term>Synergie des médicaments</term><term>Séquence conservée</term><term>Séquence d'acides aminés</term><term>Transcriptase inverse du VIH ()</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) ()</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (génétique)</term><term>Zidovudine (pharmacologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Anti-HIV Agents</term><term>Oxazepines</term><term>Pyrroles</term><term>Reverse Transcriptase Inhibitors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Anti-HIV Agents</term><term>HIV Reverse Transcriptase</term><term>Oxazepines</term><term>Pyrroles</term><term>Reverse Transcriptase Inhibitors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-HIV Agents</term><term>Oxazepines</term><term>Pyrroles</term><term>Reverse Transcriptase Inhibitors</term><term>Zidovudine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>HIV-1</term><term>Macrophages</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>HIV-1</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Agents antiVIH</term><term>Inhibiteurs de la transcriptase inverse</term><term>Oxazépines</term><term>Pyrroles</term><term>Zidovudine</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Agents antiVIH</term><term>Inhibiteurs de la transcriptase inverse</term><term>Oxazépines</term><term>Pyrroles</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Macrophages</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Binding Sites</term><term>Cells, Cultured</term><term>Conserved Sequence</term><term>Drug Design</term><term>Drug Resistance, Viral</term><term>Drug Synergism</term><term>Humans</term><term>Mice</term><term>Models, Molecular</term><term>Mutation</term><term>Stereoisomerism</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Agents antiVIH</term><term>Animaux</term><term>Cellules cultivées</term><term>Ciblage</term><term>Conception de médicament</term><term>Humains</term><term>Inhibiteurs de la transcriptase inverse</term><term>Macrophages</term><term>Modèles moléculaires</term><term>Mutation</term><term>Oxazépines</term><term>Pyrroles</term><term>Relation structure-activité</term><term>Réplication virale</term><term>Résistance virale aux médicaments</term><term>Sites de fixation</term><term>Souris</term><term>Stéréoisomérie</term><term>Synergie des médicaments</term><term>Séquence conservée</term><term>Séquence d'acides aminés</term><term>Transcriptase inverse du VIH</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term><term>Virus HIV1</term><term>RNA-directed DNA polymerase</term><term>Synthèse chimique</term><term>Relation structure activité</term><term>Inhibiteur reverse transcriptase</term><term>Composé non nucléoside</term><term>Antiviral</term><term>In vitro</term><term>Association médicamenteuse</term><term>Interaction médicamenteuse</term><term>Synergie</term><term>Zidovudine</term><term>Inhibiteur enzyme</term><term>Pyrrolobenzooxazépine</term><term>Pyrrolo[2,1-d][1,5]benzooxazépin-7-one(6-éthyl-6-[4-(phénoxyméthyl)phényl])</term><term>Lignée C8166</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Pyrrolobenzoxazepinones (PBOs) represent a new class of human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) whose prototype is 5. Molecular modeling studies based on the X-ray structures of HIV-1 RT prompted the synthesis of novel analogues which were tested as anti-HIV agents. The PBO derivatives specifically designed to target the highly conserved amino acid residues within the β12-β13 hairpin, namely primer grip, proved to be very potent against the most common mutant enzymes, including the highly resistant K103N mutant strain. Structure-activity relationships (SARs) are discussed in terms of a possible interaction with the RT binding site, depending on the nature of the substituents at C-6. Among the pyrrolobenzoxazepines investigated, 15c appeared to be the most promising NNRTI of the series characterized by potent antiviral activity, broad spectrum, and low cytotoxicity. 15c showed synergistic antiviral activity with AZT.</div></front></TEI><affiliations><list><country><li>Italie</li></country><region><li>Latium</li></region><settlement><li>Rome</li></settlement></list><tree><country name="Italie"><noRegion><name sortKey="Fattorusso, Caterina" sort="Fattorusso, Caterina" uniqKey="Fattorusso C" first="Caterina" last="Fattorusso">Caterina Fattorusso</name></noRegion><name sortKey="Bergamini, Alberto" sort="Bergamini, Alberto" uniqKey="Bergamini A" first="Alberto" last="Bergamini">Alberto Bergamini</name><name sortKey="Butini, Stefania" sort="Butini, Stefania" uniqKey="Butini S" first="Stefania" last="Butini">Stefania Butini</name><name sortKey="Butini, Stefania" sort="Butini, Stefania" uniqKey="Butini S" first="Stefania" last="Butini">Stefania Butini</name><name sortKey="Campiani, Giuseppe" sort="Campiani, Giuseppe" uniqKey="Campiani G" first="Giuseppe" last="Campiani">Giuseppe Campiani</name><name sortKey="Campiani, Giuseppe" sort="Campiani, Giuseppe" uniqKey="Campiani G" first="Giuseppe" last="Campiani">Giuseppe Campiani</name><name sortKey="Catalanotti, Bruno" sort="Catalanotti, Bruno" uniqKey="Catalanotti B" first="Bruno" last="Catalanotti">Bruno Catalanotti</name><name sortKey="Catalanotti, Bruno" sort="Catalanotti, Bruno" uniqKey="Catalanotti B" first="Bruno" last="Catalanotti">Bruno Catalanotti</name><name sortKey="Coletta, Massimo" sort="Coletta, Massimo" uniqKey="Coletta M" first="Massimo" last="Coletta">Massimo Coletta</name><name sortKey="De Angelis, Meri" sort="De Angelis, Meri" uniqKey="De Angelis M" first="Meri" last="De Angelis">Meri De Angelis</name><name sortKey="De Angelis, Meri" sort="De Angelis, Meri" uniqKey="De Angelis M" first="Meri" last="De Angelis">Meri De Angelis</name><name sortKey="Fiorini, Isabella" sort="Fiorini, Isabella" uniqKey="Fiorini I" first="Isabella" last="Fiorini">Isabella Fiorini</name><name sortKey="Fiorini, Isabella" sort="Fiorini, Isabella" uniqKey="Fiorini I" first="Isabella" last="Fiorini">Isabella Fiorini</name><name sortKey="Gemma, Sandra" sort="Gemma, Sandra" uniqKey="Gemma S" first="Sandra" last="Gemma">Sandra Gemma</name><name sortKey="Gemma, Sandra" sort="Gemma, Sandra" uniqKey="Gemma S" first="Sandra" last="Gemma">Sandra Gemma</name><name sortKey="Greco, Giovanni" sort="Greco, Giovanni" uniqKey="Greco G" first="Giovanni" last="Greco">Giovanni Greco</name><name sortKey="Huleatt, Paul" sort="Huleatt, Paul" uniqKey="Huleatt P" first="Paul" last="Huleatt">Paul Huleatt</name><name sortKey="Huleatt, Paul" sort="Huleatt, Paul" uniqKey="Huleatt P" first="Paul" last="Huleatt">Paul Huleatt</name><name sortKey="Maga, Giovanni" sort="Maga, Giovanni" uniqKey="Maga G" first="Giovanni" last="Maga">Giovanni Maga</name><name sortKey="Marini, Stefano" sort="Marini, Stefano" uniqKey="Marini S" first="Stefano" last="Marini">Stefano Marini</name><name sortKey="Nacci, V Ito" sort="Nacci, V Ito" uniqKey="Nacci V" first="V Ito" last="Nacci">V Ito Nacci</name><name sortKey="Nacci, V Ito" sort="Nacci, V Ito" uniqKey="Nacci V" first="V Ito" last="Nacci">V Ito Nacci</name><name sortKey="Novellino, Ettore" sort="Novellino, Ettore" uniqKey="Novellino E" first="Ettore" last="Novellino">Ettore Novellino</name><name sortKey="Persico, Marco" sort="Persico, Marco" uniqKey="Persico M" first="Marco" last="Persico">Marco Persico</name><name sortKey="Ramunno, Anna" sort="Ramunno, Anna" uniqKey="Ramunno A" first="Anna" last="Ramunno">Anna Ramunno</name><name sortKey="Rodriquez, Manuela" sort="Rodriquez, Manuela" uniqKey="Rodriquez M" first="Manuela" last="Rodriquez">Manuela Rodriquez</name><name sortKey="Spadari, Silvio" sort="Spadari, Silvio" uniqKey="Spadari S" first="Silvio" last="Spadari">Silvio Spadari</name><name sortKey="Spadari, Silvio" sort="Spadari, Silvio" uniqKey="Spadari S" first="Silvio" last="Spadari">Silvio Spadari</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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