Hydrophobic benzoic acids as inhibitors of influenza neuraminidase
Identifieur interne : 000074 ( PascalFrancis/Corpus ); précédent : 000073; suivant : 000075Hydrophobic benzoic acids as inhibitors of influenza neuraminidase
Auteurs : V. R. Atigadda ; W. J. Brouillette ; F. Duarte ; Y. S. Babu ; S. Bantia ; P. Chand ; NAIMING CHU ; J. A. Montgomery ; D. A. Walsh ; E. Sudbeck ; J. Finley ; G. M. Air ; MING LUO ; G. W. LaverSource :
- Bioorganic & medicinal chemistry [ 0968-0896 ] ; 1999.
Descripteurs français
- Pascal (Inist)
- Relation structure activité, Antiviral, Influenzavirus A, Inhibiteur enzyme, Exo-α-sialidase, Sélectivité, Modélisation, Modèle moléculaire, Interaction hydrophobe, Site fixation, Complexe enzyme inhibiteur, Synthèse chimique, Composé benzénique, Acide carboxylique, Guanidines, Carboxamide, Benzoïque acide(4-acétamido-3-[1-éthylpropoxy]-5-guanidino).
English descriptors
- KwdEn :
Abstract
Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A new benzoic acid inhibitor (11) containing a lipophilic side chain at C-3 and a guanidine at C-5 was synthesized. The X-ray structure of 4-(N-acetylamino)-5-guanidino-3-(3-pentyloxy)benzoic acid in complex with NA revealed that the lipophilic side chain binds in a newly created hydrophobic pocket formed by the movement of Glu 278 to interact with Arg 226, whereas the guanidine of 11 interacts in a negatively charged pocket created by Asp 152, Glu 120 and Glu 229. Compound 11 was highly selective for type A (H2N2) influenza NA (IC50 1 μM) over type B (B/Lee/40) influenza NA (IC50 500 μM).
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Format Inist (serveur)
| NO : | PASCAL 00-0077154 INIST |
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| ET : | Hydrophobic benzoic acids as inhibitors of influenza neuraminidase |
| AU : | ATIGADDA (V. R.); BROUILLETTE (W. J.); DUARTE (F.); BABU (Y. S.); BANTIA (S.); CHAND (P.); NAIMING CHU; MONTGOMERY (J. A.); WALSH (D. A.); SUDBECK (E.); FINLEY (J.); AIR (G. M.); MING LUO; LAVER (G. W.) |
| AF : | Department of Chemistry, University of Alabama at Birmingham/Birmingham, AL 35294/Etats-Unis (1 aut., 2 aut., 3 aut.); Center for Macromolecular Crystallography, University of Alabama at Birmingham/Birmingham, AL 35294/Etats-Unis (2 aut., 10 aut., 11 aut., 13 aut.); BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive/Birmingham, AL 35244/Etats-Unis (4 aut., 5 aut., 6 aut., 7 aut., 8 aut., 9 aut.); Department of Biochemistry and Molecular Biology, University of Oklahoma/Oklahoma City, OK 73190/Etats-Unis (12 aut.); John Curtin School of Medical Research, Australian National University/Canberra 2601/Australie (14 aut.) |
| DT : | Publication en série; Niveau analytique |
| SO : | Bioorganic & medicinal chemistry; ISSN 0968-0896; Royaume-Uni; Da. 1999; Vol. 7; No. 11; Pp. 2487-2497; Bibl. 33 ref. |
| LA : | Anglais |
| EA : | Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A new benzoic acid inhibitor (11) containing a lipophilic side chain at C-3 and a guanidine at C-5 was synthesized. The X-ray structure of 4-(N-acetylamino)-5-guanidino-3-(3-pentyloxy)benzoic acid in complex with NA revealed that the lipophilic side chain binds in a newly created hydrophobic pocket formed by the movement of Glu 278 to interact with Arg 226, whereas the guanidine of 11 interacts in a negatively charged pocket created by Asp 152, Glu 120 and Glu 229. Compound 11 was highly selective for type A (H2N2) influenza NA (IC50 1 μM) over type B (B/Lee/40) influenza NA (IC50 500 μM). |
| CC : | 002B02S05 |
| FD : | Relation structure activité; Antiviral; Influenzavirus A; Inhibiteur enzyme; Exo-α-sialidase; Sélectivité; Modélisation; Modèle moléculaire; Interaction hydrophobe; Site fixation; Complexe enzyme inhibiteur; Synthèse chimique; Composé benzénique; Acide carboxylique; Guanidines; Carboxamide; Benzoïque acide(4-acétamido-3-[1-éthylpropoxy]-5-guanidin o) |
| FG : | Orthomyxoviridae; Virus; O-Glycosidases; Glycosidases; Hydrolases; Enzyme |
| ED : | Structure activity relation; Antiviral; Influenzavirus A; Enzyme inhibitor; Exo-α-sialidase; Selectivity; Modeling; Molecular model; Hydrophobic interaction; Binding site; Inhibitor enzyme complex; Chemical synthesis; Benzenic compound; Carboxylic acid; Guanidines; Carboxamide |
| EG : | Orthomyxoviridae; Virus; O-Glycosidases; Glycosidases; Hydrolases; Enzyme |
| SD : | Relación estructura actividad; Antiviral; Influenzavirus A; Inhibidor enzima; Exo-α-sialidase; Selectividad; Modelización; Modelo molecular; Sitio fijación; Complejo enzima inhibidor; Síntesis química; Compuesto bencénico; Acido carboxílico; Guanidinas; Carboxamida |
| LO : | INIST-26564.354000080560130230 |
| ID : | 00-0077154 |
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Pascal:00-0077154Le document en format XML
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Chand</name><affiliation><inist:fA14 i1="03"><s1>BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive</s1><s2>Birmingham, AL 35244</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Naiming Chu" sort="Naiming Chu" uniqKey="Naiming Chu" last="Naiming Chu">NAIMING CHU</name><affiliation><inist:fA14 i1="03"><s1>BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive</s1><s2>Birmingham, AL 35244</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Montgomery, J A" sort="Montgomery, J A" uniqKey="Montgomery J" first="J. A." last="Montgomery">J. A. Montgomery</name><affiliation><inist:fA14 i1="03"><s1>BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive</s1><s2>Birmingham, AL 35244</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Walsh, D A" sort="Walsh, D A" uniqKey="Walsh D" first="D. A." last="Walsh">D. A. Walsh</name><affiliation><inist:fA14 i1="03"><s1>BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive</s1><s2>Birmingham, AL 35244</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Sudbeck, E" sort="Sudbeck, E" uniqKey="Sudbeck E" first="E." last="Sudbeck">E. Sudbeck</name><affiliation><inist:fA14 i1="02"><s1>Center for Macromolecular Crystallography, University of Alabama at Birmingham</s1><s2>Birmingham, AL 35294</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Finley, J" sort="Finley, J" uniqKey="Finley J" first="J." last="Finley">J. Finley</name><affiliation><inist:fA14 i1="02"><s1>Center for Macromolecular Crystallography, University of Alabama at Birmingham</s1><s2>Birmingham, AL 35294</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Air, G M" sort="Air, G M" uniqKey="Air G" first="G. M." last="Air">G. M. Air</name><affiliation><inist:fA14 i1="04"><s1>Department of Biochemistry and Molecular Biology, University of Oklahoma</s1><s2>Oklahoma City, OK 73190</s2><s3>USA</s3><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ming Luo" sort="Ming Luo" uniqKey="Ming Luo" last="Ming Luo">MING LUO</name><affiliation><inist:fA14 i1="02"><s1>Center for Macromolecular Crystallography, University of Alabama at Birmingham</s1><s2>Birmingham, AL 35294</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Laver, G W" sort="Laver, G W" uniqKey="Laver G" first="G. W." last="Laver">G. W. Laver</name><affiliation><inist:fA14 i1="05"><s1>John Curtin School of Medical Research, Australian National University</s1><s2>Canberra 2601</s2><s3>AUS</s3><sZ>14 aut.</sZ></inist:fA14></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">00-0077154</idno><date when="1999">1999</date><idno type="stanalyst">PASCAL 00-0077154 INIST</idno><idno type="RBID">Pascal:00-0077154</idno><idno type="wicri:Area/PascalFrancis/Corpus">000074</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Hydrophobic benzoic acids as inhibitors of influenza neuraminidase</title><author><name sortKey="Atigadda, V R" sort="Atigadda, V R" uniqKey="Atigadda V" first="V. R." last="Atigadda">V. R. Atigadda</name><affiliation><inist:fA14 i1="01"><s1>Department of Chemistry, University of Alabama at Birmingham</s1><s2>Birmingham, AL 35294</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Brouillette, W J" sort="Brouillette, W J" uniqKey="Brouillette W" first="W. J." last="Brouillette">W. J. Brouillette</name><affiliation><inist:fA14 i1="01"><s1>Department of Chemistry, University of Alabama at Birmingham</s1><s2>Birmingham, AL 35294</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="02"><s1>Center for Macromolecular Crystallography, University of Alabama at Birmingham</s1><s2>Birmingham, AL 35294</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Duarte, F" sort="Duarte, F" uniqKey="Duarte F" first="F." last="Duarte">F. Duarte</name><affiliation><inist:fA14 i1="01"><s1>Department of Chemistry, University of Alabama at Birmingham</s1><s2>Birmingham, AL 35294</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Babu, Y S" sort="Babu, Y S" uniqKey="Babu Y" first="Y. S." last="Babu">Y. S. Babu</name><affiliation><inist:fA14 i1="03"><s1>BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive</s1><s2>Birmingham, AL 35244</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Bantia, S" sort="Bantia, S" uniqKey="Bantia S" first="S." last="Bantia">S. Bantia</name><affiliation><inist:fA14 i1="03"><s1>BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive</s1><s2>Birmingham, AL 35244</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Chand, P" sort="Chand, P" uniqKey="Chand P" first="P." last="Chand">P. Chand</name><affiliation><inist:fA14 i1="03"><s1>BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive</s1><s2>Birmingham, AL 35244</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Naiming Chu" sort="Naiming Chu" uniqKey="Naiming Chu" last="Naiming Chu">NAIMING CHU</name><affiliation><inist:fA14 i1="03"><s1>BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive</s1><s2>Birmingham, AL 35244</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Montgomery, J A" sort="Montgomery, J A" uniqKey="Montgomery J" first="J. A." last="Montgomery">J. A. Montgomery</name><affiliation><inist:fA14 i1="03"><s1>BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive</s1><s2>Birmingham, AL 35244</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Walsh, D A" sort="Walsh, D A" uniqKey="Walsh D" first="D. A." last="Walsh">D. A. Walsh</name><affiliation><inist:fA14 i1="03"><s1>BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive</s1><s2>Birmingham, AL 35244</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Sudbeck, E" sort="Sudbeck, E" uniqKey="Sudbeck E" first="E." last="Sudbeck">E. Sudbeck</name><affiliation><inist:fA14 i1="02"><s1>Center for Macromolecular Crystallography, University of Alabama at Birmingham</s1><s2>Birmingham, AL 35294</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Finley, J" sort="Finley, J" uniqKey="Finley J" first="J." last="Finley">J. Finley</name><affiliation><inist:fA14 i1="02"><s1>Center for Macromolecular Crystallography, University of Alabama at Birmingham</s1><s2>Birmingham, AL 35294</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Air, G M" sort="Air, G M" uniqKey="Air G" first="G. M." last="Air">G. M. Air</name><affiliation><inist:fA14 i1="04"><s1>Department of Biochemistry and Molecular Biology, University of Oklahoma</s1><s2>Oklahoma City, OK 73190</s2><s3>USA</s3><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Ming Luo" sort="Ming Luo" uniqKey="Ming Luo" last="Ming Luo">MING LUO</name><affiliation><inist:fA14 i1="02"><s1>Center for Macromolecular Crystallography, University of Alabama at Birmingham</s1><s2>Birmingham, AL 35294</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Laver, G W" sort="Laver, G W" uniqKey="Laver G" first="G. W." last="Laver">G. W. Laver</name><affiliation><inist:fA14 i1="05"><s1>John Curtin School of Medical Research, Australian National University</s1><s2>Canberra 2601</s2><s3>AUS</s3><sZ>14 aut.</sZ></inist:fA14></affiliation></author></analytic><series><title level="j" type="main">Bioorganic & medicinal chemistry</title><title level="j" type="abbreviated">Bioorg. med. chem.</title><idno type="ISSN">0968-0896</idno><imprint><date when="1999">1999</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Bioorganic & medicinal chemistry</title><title level="j" type="abbreviated">Bioorg. med. chem.</title><idno type="ISSN">0968-0896</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral</term><term>Benzenic compound</term><term>Binding site</term><term>Carboxamide</term><term>Carboxylic acid</term><term>Chemical synthesis</term><term>Enzyme inhibitor</term><term>Exo-α-sialidase</term><term>Guanidines</term><term>Hydrophobic interaction</term><term>Influenzavirus A</term><term>Inhibitor enzyme complex</term><term>Modeling</term><term>Molecular model</term><term>Selectivity</term><term>Structure activity relation</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Relation structure activité</term><term>Antiviral</term><term>Influenzavirus A</term><term>Inhibiteur enzyme</term><term>Exo-α-sialidase</term><term>Sélectivité</term><term>Modélisation</term><term>Modèle moléculaire</term><term>Interaction hydrophobe</term><term>Site fixation</term><term>Complexe enzyme inhibiteur</term><term>Synthèse chimique</term><term>Composé benzénique</term><term>Acide carboxylique</term><term>Guanidines</term><term>Carboxamide</term><term>Benzoïque acide(4-acétamido-3-[1-éthylpropoxy]-5-guanidino)</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A new benzoic acid inhibitor (11) containing a lipophilic side chain at C-3 and a guanidine at C-5 was synthesized. The X-ray structure of 4-(N-acetylamino)-5-guanidino-3-(3-pentyloxy)benzoic acid in complex with NA revealed that the lipophilic side chain binds in a newly created hydrophobic pocket formed by the movement of Glu 278 to interact with Arg 226, whereas the guanidine of 11 interacts in a negatively charged pocket created by Asp 152, Glu 120 and Glu 229. Compound 11 was highly selective for type A (H2N2) influenza NA (IC<sub>50</sub> 1 μM) over type B (B/Lee/40) influenza NA (IC<sub>50</sub> 500 μM).</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0968-0896</s0></fA01><fA03 i2="1"><s0>Bioorg. med. chem.</s0></fA03><fA05><s2>7</s2></fA05><fA06><s2>11</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Hydrophobic benzoic acids as inhibitors of influenza neuraminidase</s1></fA08><fA11 i1="01" i2="1"><s1>ATIGADDA (V. R.)</s1></fA11><fA11 i1="02" i2="1"><s1>BROUILLETTE (W. J.)</s1></fA11><fA11 i1="03" i2="1"><s1>DUARTE (F.)</s1></fA11><fA11 i1="04" i2="1"><s1>BABU (Y. S.)</s1></fA11><fA11 i1="05" i2="1"><s1>BANTIA (S.)</s1></fA11><fA11 i1="06" i2="1"><s1>CHAND (P.)</s1></fA11><fA11 i1="07" i2="1"><s1>NAIMING CHU</s1></fA11><fA11 i1="08" i2="1"><s1>MONTGOMERY (J. A.)</s1></fA11><fA11 i1="09" i2="1"><s1>WALSH (D. A.)</s1></fA11><fA11 i1="10" i2="1"><s1>SUDBECK (E.)</s1></fA11><fA11 i1="11" i2="1"><s1>FINLEY (J.)</s1></fA11><fA11 i1="12" i2="1"><s1>AIR (G. M.)</s1></fA11><fA11 i1="13" i2="1"><s1>MING LUO</s1></fA11><fA11 i1="14" i2="1"><s1>LAVER (G. W.)</s1></fA11><fA14 i1="01"><s1>Department of Chemistry, University of Alabama at Birmingham</s1><s2>Birmingham, AL 35294</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ></fA14><fA14 i1="02"><s1>Center for Macromolecular Crystallography, University of Alabama at Birmingham</s1><s2>Birmingham, AL 35294</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></fA14><fA14 i1="03"><s1>BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive</s1><s2>Birmingham, AL 35244</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Biochemistry and Molecular Biology, University of Oklahoma</s1><s2>Oklahoma City, OK 73190</s2><s3>USA</s3><sZ>12 aut.</sZ></fA14><fA14 i1="05"><s1>John Curtin School of Medical Research, Australian National University</s1><s2>Canberra 2601</s2><s3>AUS</s3><sZ>14 aut.</sZ></fA14><fA20><s1>2487-2497</s1></fA20><fA21><s1>1999</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>26564</s2><s5>354000080560130230</s5></fA43><fA44><s0>0000</s0><s1>© 2000 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>33 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>00-0077154</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Bioorganic & medicinal chemistry</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A new benzoic acid inhibitor (11) containing a lipophilic side chain at C-3 and a guanidine at C-5 was synthesized. The X-ray structure of 4-(N-acetylamino)-5-guanidino-3-(3-pentyloxy)benzoic acid in complex with NA revealed that the lipophilic side chain binds in a newly created hydrophobic pocket formed by the movement of Glu 278 to interact with Arg 226, whereas the guanidine of 11 interacts in a negatively charged pocket created by Asp 152, Glu 120 and Glu 229. Compound 11 was highly selective for type A (H2N2) influenza NA (IC<sub>50</sub> 1 μM) over type B (B/Lee/40) influenza NA (IC<sub>50</sub> 500 μM).</s0></fC01><fC02 i1="01" i2="X"><s0>002B02S05</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Relation structure activité</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Structure activity relation</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Relación estructura actividad</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Antiviral</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Antiviral</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Antiviral</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Influenzavirus A</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Influenzavirus A</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Influenzavirus A</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Inhibiteur enzyme</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Enzyme inhibitor</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Inhibidor enzima</s0><s5>04</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Exo-α-sialidase</s0><s2>FE</s2><s5>05</s5><s6>Exo-«α»-sialidase</s6></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Exo-α-sialidase</s0><s2>FE</s2><s5>05</s5><s6>Exo-«α»-sialidase</s6></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Exo-α-sialidase</s0><s2>FE</s2><s5>05</s5><s6>Exo-«α»-sialidase</s6></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Sélectivité</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Selectivity</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Selectividad</s0><s5>06</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Modélisation</s0><s5>08</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Modeling</s0><s5>08</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Modelización</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Modèle moléculaire</s0><s5>09</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Molecular model</s0><s5>09</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Modelo molecular</s0><s5>09</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Interaction hydrophobe</s0><s5>10</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Hydrophobic interaction</s0><s5>10</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Site fixation</s0><s5>11</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Binding site</s0><s5>11</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Sitio fijación</s0><s5>11</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>Complexe enzyme inhibiteur</s0><s5>12</s5></fC03><fC03 i1="11" i2="X" l="ENG"><s0>Inhibitor enzyme complex</s0><s5>12</s5></fC03><fC03 i1="11" i2="X" l="SPA"><s0>Complejo enzima inhibidor</s0><s5>12</s5></fC03><fC03 i1="12" i2="X" l="FRE"><s0>Synthèse chimique</s0><s5>13</s5></fC03><fC03 i1="12" i2="X" l="ENG"><s0>Chemical synthesis</s0><s5>13</s5></fC03><fC03 i1="12" i2="X" l="SPA"><s0>Síntesis química</s0><s5>13</s5></fC03><fC03 i1="13" i2="X" l="FRE"><s0>Composé benzénique</s0><s5>15</s5></fC03><fC03 i1="13" i2="X" l="ENG"><s0>Benzenic compound</s0><s5>15</s5></fC03><fC03 i1="13" i2="X" l="SPA"><s0>Compuesto bencénico</s0><s5>15</s5></fC03><fC03 i1="14" i2="X" l="FRE"><s0>Acide carboxylique</s0><s5>16</s5></fC03><fC03 i1="14" i2="X" l="ENG"><s0>Carboxylic acid</s0><s5>16</s5></fC03><fC03 i1="14" i2="X" l="SPA"><s0>Acido carboxílico</s0><s5>16</s5></fC03><fC03 i1="15" i2="X" l="FRE"><s0>Guanidines</s0><s5>17</s5></fC03><fC03 i1="15" i2="X" l="ENG"><s0>Guanidines</s0><s5>17</s5></fC03><fC03 i1="15" i2="X" l="SPA"><s0>Guanidinas</s0><s5>17</s5></fC03><fC03 i1="16" i2="X" l="FRE"><s0>Carboxamide</s0><s5>18</s5></fC03><fC03 i1="16" i2="X" l="ENG"><s0>Carboxamide</s0><s5>18</s5></fC03><fC03 i1="16" i2="X" l="SPA"><s0>Carboxamida</s0><s5>18</s5></fC03><fC03 i1="17" i2="X" l="FRE"><s0>Benzoïque acide(4-acétamido-3-[1-éthylpropoxy]-5-guanidino)</s0><s2>NK</s2><s2>FR</s2><s4>INC</s4><s5>62</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>O-Glycosidases</s0><s2>FE</s2><s6>«O»-Glycosidases</s6></fC07><fC07 i1="03" i2="X" l="ENG"><s0>O-Glycosidases</s0><s2>FE</s2><s6>«O»-Glycosidases</s6></fC07><fC07 i1="03" i2="X" l="SPA"><s0>O-Glycosidases</s0><s2>FE</s2><s6>«O»-Glycosidases</s6></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Glycosidases</s0><s2>FE</s2></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Glycosidases</s0><s2>FE</s2></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Glycosidases</s0><s2>FE</s2></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Hydrolases</s0><s2>FE</s2></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Hydrolases</s0><s2>FE</s2></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Hydrolases</s0><s2>FE</s2></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Enzyme</s0></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Enzyme</s0></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Enzima</s0></fC07><fN21><s1>052</s1></fN21></pA></standard><server><NO>PASCAL 00-0077154 INIST</NO><ET>Hydrophobic benzoic acids as inhibitors of influenza neuraminidase</ET><AU>ATIGADDA (V. R.); BROUILLETTE (W. J.); DUARTE (F.); BABU (Y. S.); BANTIA (S.); CHAND (P.); NAIMING CHU; MONTGOMERY (J. A.); WALSH (D. A.); SUDBECK (E.); FINLEY (J.); AIR (G. M.); MING LUO; LAVER (G. W.)</AU><AF>Department of Chemistry, University of Alabama at Birmingham/Birmingham, AL 35294/Etats-Unis (1 aut., 2 aut., 3 aut.); Center for Macromolecular Crystallography, University of Alabama at Birmingham/Birmingham, AL 35294/Etats-Unis (2 aut., 10 aut., 11 aut., 13 aut.); BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive/Birmingham, AL 35244/Etats-Unis (4 aut., 5 aut., 6 aut., 7 aut., 8 aut., 9 aut.); Department of Biochemistry and Molecular Biology, University of Oklahoma/Oklahoma City, OK 73190/Etats-Unis (12 aut.); John Curtin School of Medical Research, Australian National University/Canberra 2601/Australie (14 aut.)</AF><DT>Publication en série; Niveau analytique</DT><SO>Bioorganic & medicinal chemistry; ISSN 0968-0896; Royaume-Uni; Da. 1999; Vol. 7; No. 11; Pp. 2487-2497; Bibl. 33 ref.</SO><LA>Anglais</LA><EA>Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A new benzoic acid inhibitor (11) containing a lipophilic side chain at C-3 and a guanidine at C-5 was synthesized. The X-ray structure of 4-(N-acetylamino)-5-guanidino-3-(3-pentyloxy)benzoic acid in complex with NA revealed that the lipophilic side chain binds in a newly created hydrophobic pocket formed by the movement of Glu 278 to interact with Arg 226, whereas the guanidine of 11 interacts in a negatively charged pocket created by Asp 152, Glu 120 and Glu 229. Compound 11 was highly selective for type A (H2N2) influenza NA (IC<sub>50</sub> 1 μM) over type B (B/Lee/40) influenza NA (IC<sub>50</sub> 500 μM).</EA><CC>002B02S05</CC><FD>Relation structure activité; Antiviral; Influenzavirus A; Inhibiteur enzyme; Exo-α-sialidase; Sélectivité; Modélisation; Modèle moléculaire; Interaction hydrophobe; Site fixation; Complexe enzyme inhibiteur; Synthèse chimique; Composé benzénique; Acide carboxylique; Guanidines; Carboxamide; Benzoïque acide(4-acétamido-3-[1-éthylpropoxy]-5-guanidin o)</FD><FG>Orthomyxoviridae; Virus; O-Glycosidases; Glycosidases; Hydrolases; Enzyme</FG><ED>Structure activity relation; Antiviral; Influenzavirus A; Enzyme inhibitor; Exo-α-sialidase; Selectivity; Modeling; Molecular model; Hydrophobic interaction; Binding site; Inhibitor enzyme complex; Chemical synthesis; Benzenic compound; Carboxylic acid; Guanidines; Carboxamide</ED><EG>Orthomyxoviridae; Virus; O-Glycosidases; Glycosidases; Hydrolases; Enzyme</EG><SD>Relación estructura actividad; Antiviral; Influenzavirus A; Inhibidor enzima; Exo-α-sialidase; Selectividad; Modelización; Modelo molecular; Sitio fijación; Complejo enzima inhibidor; Síntesis química; Compuesto bencénico; Acido carboxílico; Guanidinas; Carboxamida</SD><LO>INIST-26564.354000080560130230</LO><ID>00-0077154</ID></server></inist></record>Pour manipuler ce document sous Unix (Dilib)
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