Design, Synthesis, and SAR of C-3 Benzoic Acid, C-17 Triterpenoid Derivatives. Identification of the HIV-1 Maturation Inhibitor 4-((1 R,3a S,5a R,5b R,7a R,11a S,11b R,13a R,13b R)-3a-((2-(1,1-Dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1 H-cyclopenta[ a]chrysen-9-yl)benzoic Acid (GSK3532795, BMS-955176).
Identifieur interne : 000988 ( PubMed/Corpus ); précédent : 000987; suivant : 000989Design, Synthesis, and SAR of C-3 Benzoic Acid, C-17 Triterpenoid Derivatives. Identification of the HIV-1 Maturation Inhibitor 4-((1 R,3a S,5a R,5b R,7a R,11a S,11b R,13a R,13b R)-3a-((2-(1,1-Dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1 H-cyclopenta[ a]chrysen-9-yl)benzoic Acid (GSK3532795, BMS-955176).
Auteurs : Alicia Regueiro-Ren ; Jacob J. Swidorski ; Zheng Liu ; Yan Chen ; Ny Sin ; Sing-Yuen Sit ; Jie Chen ; Brian L. Venables ; Juliang Zhu ; Beata Nowicka-Sans ; Tricia Protack ; Zeyu Lin ; Brian Terry ; Himadri Samanta ; Sharon Zhang ; Zhufang Li ; John Easter ; Brett R. Beno ; Vinod Arora ; Xiaohua S. Huang ; Sandhya Rahematpura ; Dawn D. Parker ; Roy Haskell ; Kenneth S. Santone ; Mark I. Cockett ; Mark Krystal ; Nicholas A. Meanwell ; Susan Jenkins ; Umesh Hanumegowda ; Ira B. DickerSource :
- Journal of medicinal chemistry [ 1520-4804 ] ; 2018.
English descriptors
- KwdEn :
- ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics), Administration, Oral, Animals, Anti-HIV Agents (chemistry), Anti-HIV Agents (pharmacokinetics), Anti-HIV Agents (pharmacology), Benzoic Acid (chemistry), Biological Availability, Chemistry Techniques, Synthetic, Chrysenes (chemistry), Chrysenes (pharmacology), Dogs, Drug Design, Drug Stability, HIV-1 (drug effects), HIV-1 (genetics), Humans, Macaca fascicularis, Male, Mice, Inbred Strains, Mice, Knockout, Microsomes, Liver (drug effects), Morpholines (chemistry), Morpholines (pharmacology), Polymorphism, Genetic, Rats, Sprague-Dawley, Structure-Activity Relationship, Triterpenes (chemistry), Triterpenes (pharmacology).
- MESH :
- chemical , chemistry : Anti-HIV Agents, Benzoic Acid, Chrysenes, Morpholines, Triterpenes.
- chemical , genetics : ATP Binding Cassette Transporter, Subfamily B, Member 1.
- chemical , pharmacokinetics : Anti-HIV Agents.
- chemical , pharmacology : Anti-HIV Agents, Chrysenes, Morpholines, Triterpenes.
- drug effects : HIV-1, Microsomes, Liver.
- genetics : HIV-1.
- Administration, Oral, Animals, Biological Availability, Chemistry Techniques, Synthetic, Dogs, Drug Design, Drug Stability, Humans, Macaca fascicularis, Male, Mice, Inbred Strains, Mice, Knockout, Polymorphism, Genetic, Rats, Sprague-Dawley, Structure-Activity Relationship.
Abstract
GSK3532795, formerly known as BMS-955176 (1), is a potent, orally active, second-generation HIV-1 maturation inhibitor (MI) that advanced through phase IIb clinical trials. The careful design, selection, and evaluation of substituents appended to the C-3 and C-17 positions of the natural product betulinic acid (3) was critical in attaining a molecule with the desired virological and pharmacokinetic profile. Herein, we highlight the key insights made in the discovery program and detail the evolution of the structure-activity relationships (SARs) that led to the design of the specific C-17 amine moiety in 1. These modifications ultimately enabled the discovery of 1 as a second-generation MI that combines broad coverage of polymorphic viruses (EC50 <15 nM toward a panel of common polymorphisms representative of 96.5% HIV-1 subtype B virus) with a favorable pharmacokinetic profile in preclinical species.
DOI: 10.1021/acs.jmedchem.8b00854
PubMed: 30067361
Links to Exploration step
pubmed:30067361Le document en format XML
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Swidorski</name></author><author><name sortKey="Liu, Zheng" sort="Liu, Zheng" uniqKey="Liu Z" first="Zheng" last="Liu">Zheng Liu</name></author><author><name sortKey="Chen, Yan" sort="Chen, Yan" uniqKey="Chen Y" first="Yan" last="Chen">Yan Chen</name></author><author><name sortKey="Sin, Ny" sort="Sin, Ny" uniqKey="Sin N" first="Ny" last="Sin">Ny Sin</name></author><author><name sortKey="Sit, Sing Yuen" sort="Sit, Sing Yuen" uniqKey="Sit S" first="Sing-Yuen" last="Sit">Sing-Yuen Sit</name></author><author><name sortKey="Chen, Jie" sort="Chen, Jie" uniqKey="Chen J" first="Jie" last="Chen">Jie Chen</name></author><author><name sortKey="Venables, Brian L" sort="Venables, Brian L" uniqKey="Venables B" first="Brian L" last="Venables">Brian L. 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Identification of the HIV-1 Maturation Inhibitor 4-((1 R,3a S,5a R,5b R,7a R,11a S,11b R,13a R,13b R)-3a-((2-(1,1-Dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1 H-cyclopenta[ a]chrysen-9-yl)benzoic Acid (GSK3532795, BMS-955176).</title><author><name sortKey="Regueiro Ren, Alicia" sort="Regueiro Ren, Alicia" uniqKey="Regueiro Ren A" first="Alicia" last="Regueiro-Ren">Alicia Regueiro-Ren</name></author><author><name sortKey="Swidorski, Jacob J" sort="Swidorski, Jacob J" uniqKey="Swidorski J" first="Jacob J" last="Swidorski">Jacob J. 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Beno</name></author><author><name sortKey="Arora, Vinod" sort="Arora, Vinod" uniqKey="Arora V" first="Vinod" last="Arora">Vinod Arora</name></author><author><name sortKey="Huang, Xiaohua S" sort="Huang, Xiaohua S" uniqKey="Huang X" first="Xiaohua S" last="Huang">Xiaohua S. Huang</name></author><author><name sortKey="Rahematpura, Sandhya" sort="Rahematpura, Sandhya" uniqKey="Rahematpura S" first="Sandhya" last="Rahematpura">Sandhya Rahematpura</name></author><author><name sortKey="Parker, Dawn D" sort="Parker, Dawn D" uniqKey="Parker D" first="Dawn D" last="Parker">Dawn D. Parker</name></author><author><name sortKey="Haskell, Roy" sort="Haskell, Roy" uniqKey="Haskell R" first="Roy" last="Haskell">Roy Haskell</name></author><author><name sortKey="Santone, Kenneth S" sort="Santone, Kenneth S" uniqKey="Santone K" first="Kenneth S" last="Santone">Kenneth S. Santone</name></author><author><name sortKey="Cockett, Mark I" sort="Cockett, Mark I" uniqKey="Cockett M" first="Mark I" last="Cockett">Mark I. Cockett</name></author><author><name sortKey="Krystal, Mark" sort="Krystal, Mark" uniqKey="Krystal M" first="Mark" last="Krystal">Mark Krystal</name></author><author><name sortKey="Meanwell, Nicholas A" sort="Meanwell, Nicholas A" uniqKey="Meanwell N" first="Nicholas A" last="Meanwell">Nicholas A. Meanwell</name></author><author><name sortKey="Jenkins, Susan" sort="Jenkins, Susan" uniqKey="Jenkins S" first="Susan" last="Jenkins">Susan Jenkins</name></author><author><name sortKey="Hanumegowda, Umesh" sort="Hanumegowda, Umesh" uniqKey="Hanumegowda U" first="Umesh" last="Hanumegowda">Umesh Hanumegowda</name></author><author><name sortKey="Dicker, Ira B" sort="Dicker, Ira B" uniqKey="Dicker I" first="Ira B" last="Dicker">Ira B. Dicker</name></author></analytic><series><title level="j">Journal of medicinal chemistry</title><idno type="eISSN">1520-4804</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)</term><term>Administration, Oral</term><term>Animals</term><term>Anti-HIV Agents (chemistry)</term><term>Anti-HIV Agents (pharmacokinetics)</term><term>Anti-HIV Agents (pharmacology)</term><term>Benzoic Acid (chemistry)</term><term>Biological Availability</term><term>Chemistry Techniques, Synthetic</term><term>Chrysenes (chemistry)</term><term>Chrysenes (pharmacology)</term><term>Dogs</term><term>Drug Design</term><term>Drug Stability</term><term>HIV-1 (drug effects)</term><term>HIV-1 (genetics)</term><term>Humans</term><term>Macaca fascicularis</term><term>Male</term><term>Mice, Inbred Strains</term><term>Mice, Knockout</term><term>Microsomes, Liver (drug effects)</term><term>Morpholines (chemistry)</term><term>Morpholines (pharmacology)</term><term>Polymorphism, Genetic</term><term>Rats, Sprague-Dawley</term><term>Structure-Activity Relationship</term><term>Triterpenes (chemistry)</term><term>Triterpenes (pharmacology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Anti-HIV Agents</term><term>Benzoic Acid</term><term>Chrysenes</term><term>Morpholines</term><term>Triterpenes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>ATP Binding Cassette Transporter, Subfamily B, Member 1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Anti-HIV Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-HIV Agents</term><term>Chrysenes</term><term>Morpholines</term><term>Triterpenes</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>HIV-1</term><term>Microsomes, Liver</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>HIV-1</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Oral</term><term>Animals</term><term>Biological Availability</term><term>Chemistry Techniques, Synthetic</term><term>Dogs</term><term>Drug Design</term><term>Drug Stability</term><term>Humans</term><term>Macaca fascicularis</term><term>Male</term><term>Mice, Inbred Strains</term><term>Mice, Knockout</term><term>Polymorphism, Genetic</term><term>Rats, Sprague-Dawley</term><term>Structure-Activity Relationship</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">GSK3532795, formerly known as BMS-955176 (1), is a potent, orally active, second-generation HIV-1 maturation inhibitor (MI) that advanced through phase IIb clinical trials. The careful design, selection, and evaluation of substituents appended to the C-3 and C-17 positions of the natural product betulinic acid (3) was critical in attaining a molecule with the desired virological and pharmacokinetic profile. Herein, we highlight the key insights made in the discovery program and detail the evolution of the structure-activity relationships (SARs) that led to the design of the specific C-17 amine moiety in 1. These modifications ultimately enabled the discovery of 1 as a second-generation MI that combines broad coverage of polymorphic viruses (EC<sub>50</sub> <15 nM toward a panel of common polymorphisms representative of 96.5% HIV-1 subtype B virus) with a favorable pharmacokinetic profile in preclinical species.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30067361</PMID><DateCompleted><Year>2019</Year><Month>10</Month><Day>14</Day></DateCompleted><DateRevised><Year>2020</Year><Month>03</Month><Day>17</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1520-4804</ISSN><JournalIssue CitedMedium="Internet"><Volume>61</Volume><Issue>16</Issue><PubDate><Year>2018</Year><Month>08</Month><Day>23</Day></PubDate></JournalIssue><Title>Journal of medicinal chemistry</Title><ISOAbbreviation>J. Med. Chem.</ISOAbbreviation></Journal><ArticleTitle>Design, Synthesis, and SAR of C-3 Benzoic Acid, C-17 Triterpenoid Derivatives. Identification of the HIV-1 Maturation Inhibitor 4-((1 R,3a S,5a R,5b R,7a R,11a S,11b R,13a R,13b R)-3a-((2-(1,1-Dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1 H-cyclopenta[ a]chrysen-9-yl)benzoic Acid (GSK3532795, BMS-955176).</ArticleTitle><Pagination><MedlinePgn>7289-7313</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1021/acs.jmedchem.8b00854</ELocationID><Abstract><AbstractText>GSK3532795, formerly known as BMS-955176 (1), is a potent, orally active, second-generation HIV-1 maturation inhibitor (MI) that advanced through phase IIb clinical trials. The careful design, selection, and evaluation of substituents appended to the C-3 and C-17 positions of the natural product betulinic acid (3) was critical in attaining a molecule with the desired virological and pharmacokinetic profile. Herein, we highlight the key insights made in the discovery program and detail the evolution of the structure-activity relationships (SARs) that led to the design of the specific C-17 amine moiety in 1. These modifications ultimately enabled the discovery of 1 as a second-generation MI that combines broad coverage of polymorphic viruses (EC<sub>50</sub> <15 nM toward a panel of common polymorphisms representative of 96.5% HIV-1 subtype B virus) with a favorable pharmacokinetic profile in preclinical species.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Regueiro-Ren</LastName><ForeName>Alicia</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0003-2991-719X</Identifier></Author><Author ValidYN="Y"><LastName>Swidorski</LastName><ForeName>Jacob J</ForeName><Initials>JJ</Initials></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Zheng</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Yan</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Sin</LastName><ForeName>Ny</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Sit</LastName><ForeName>Sing-Yuen</ForeName><Initials>SY</Initials></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Jie</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Venables</LastName><ForeName>Brian L</ForeName><Initials>BL</Initials></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Juliang</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Nowicka-Sans</LastName><ForeName>Beata</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Protack</LastName><ForeName>Tricia</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Zeyu</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>Terry</LastName><ForeName>Brian</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Samanta</LastName><ForeName>Himadri</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Sharon</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Zhufang</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>Easter</LastName><ForeName>John</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Beno</LastName><ForeName>Brett R</ForeName><Initials>BR</Initials></Author><Author ValidYN="Y"><LastName>Arora</LastName><ForeName>Vinod</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Xiaohua S</ForeName><Initials>XS</Initials></Author><Author ValidYN="Y"><LastName>Rahematpura</LastName><ForeName>Sandhya</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Parker</LastName><ForeName>Dawn D</ForeName><Initials>DD</Initials></Author><Author ValidYN="Y"><LastName>Haskell</LastName><ForeName>Roy</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Santone</LastName><ForeName>Kenneth S</ForeName><Initials>KS</Initials></Author><Author ValidYN="Y"><LastName>Cockett</LastName><ForeName>Mark I</ForeName><Initials>MI</Initials></Author><Author ValidYN="Y"><LastName>Krystal</LastName><ForeName>Mark</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Meanwell</LastName><ForeName>Nicholas A</ForeName><Initials>NA</Initials><Identifier Source="ORCID">0000-0002-8857-1515</Identifier></Author><Author ValidYN="Y"><LastName>Jenkins</LastName><ForeName>Susan</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Hanumegowda</LastName><ForeName>Umesh</ForeName><Initials>U</Initials></Author><Author ValidYN="Y"><LastName>Dicker</LastName><ForeName>Ira B</ForeName><Initials>IB</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>08</Month><Day>01</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Med Chem</MedlineTA><NlmUniqueID>9716531</NlmUniqueID><ISSNLinking>0022-2623</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D020168">ATP Binding Cassette Transporter, Subfamily B, Member 1</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019380">Anti-HIV Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002911">Chrysenes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009025">Morpholines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014315">Triterpenes</NameOfSubstance></Chemical><Chemical><RegistryNumber>4CA9IAU7RJ</RegistryNumber><NameOfSubstance UI="C000627567">BMS-955176</NameOfSubstance></Chemical><Chemical><RegistryNumber>8SKN0B0MIM</RegistryNumber><NameOfSubstance UI="D019817">Benzoic Acid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D020168" MajorTopicYN="N">ATP Binding Cassette Transporter, Subfamily B, Member 1</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000284" MajorTopicYN="N">Administration, Oral</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019380" MajorTopicYN="N">Anti-HIV Agents</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019817" MajorTopicYN="N">Benzoic Acid</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001682" MajorTopicYN="N">Biological Availability</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D060326" MajorTopicYN="N">Chemistry Techniques, Synthetic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002911" MajorTopicYN="N">Chrysenes</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004285" MajorTopicYN="N">Dogs</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015195" MajorTopicYN="N">Drug Design</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004355" MajorTopicYN="N">Drug Stability</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015497" MajorTopicYN="N">HIV-1</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008252" MajorTopicYN="N">Macaca fascicularis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008815" MajorTopicYN="N">Mice, Inbred Strains</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008862" MajorTopicYN="N">Microsomes, Liver</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009025" MajorTopicYN="N">Morpholines</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011110" MajorTopicYN="N">Polymorphism, Genetic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013329" MajorTopicYN="Y">Structure-Activity Relationship</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014315" MajorTopicYN="N">Triterpenes</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>8</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>10</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>8</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30067361</ArticleId><ArticleId IdType="doi">10.1021/acs.jmedchem.8b00854</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Design, Synthesis, and SAR of C-3 Benzoic Acid, C-17 Triterpenoid Derivatives. Identification of the HIV-1 Maturation Inhibitor 4-((1 R,3a S,5a R,5b R,7a R,11a S,11b R,13a R,13b R)-3a-((2-(1,1-Dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1 H-cyclopenta[ a]chrysen-9-yl)benzoic Acid (GSK3532795, BMS-955176).
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