Combinatorial synthesis of CCR5 antagonists
Herein we report the preparation of a combinatorial library of compounds with potent CCR5 binding affinity. The library design was aided by SAR generated in a traditional medicinal chemistry effort. Compounds with novel combinations of subunits were discovered that have high binding affinity for the...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2001-12, Vol.11 (24), p.3137-3141 |
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| container_end_page | 3141 |
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| container_issue | 24 |
| container_start_page | 3137 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 11 |
| creator | Willoughby, Christopher A Berk, Scott C Rosauer, Keith G Degrado, Silvia Chapman, Kevin T Gould, Sandra L Springer, Martin S Malkowitz, Lorraine Schleif, William A Hazuda, Daria Miller, Michael Kessler, Joseph Danzeisen, Renee Holmes, Karen Lineberger, Janet Carella, Anthony Carver, Gwen Emini, Emilio A |
| description | Herein we report the preparation of a combinatorial library of compounds with potent CCR5 binding affinity. The library design was aided by SAR generated in a traditional medicinal chemistry effort. Compounds with novel combinations of subunits were discovered that have high binding affinity for the CCR5 receptor. A potent CCR5 antagonist from the library, compound
11 was found to have moderate anti-HIV-1 activity.
The synthesis of the combinatorial library of CCR5 antagonists is reported. Compound
2 was discovered, which has a 1
nM IC
50 in a CCR5 binding assay and inhibits HIV-1 replication with an IC
95 of 580
nM. |
| doi_str_mv | 10.1016/S0960-894X(01)00652-7 |
| format | Article |
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11 was found to have moderate anti-HIV-1 activity.
The synthesis of the combinatorial library of CCR5 antagonists is reported. Compound
2 was discovered, which has a 1
nM IC
50 in a CCR5 binding assay and inhibits HIV-1 replication with an IC
95 of 580
nM.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/S0960-894X(01)00652-7</identifier><identifier>PMID: 11720860</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Biological and medical sciences ; CCR5 Receptor Antagonists ; Combinatorial Chemistry Techniques ; HIV-1 - drug effects ; Medical sciences ; Pharmacology. Drug treatments ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry letters, 2001-12, Vol.11 (24), p.3137-3141</ispartof><rights>2001 Elsevier Science Ltd</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-fe3ef7a9f68543d410a07dcdfed62de1ecdbe536467ac81a5bc8509b4ab790f13</citedby><cites>FETCH-LOGICAL-c391t-fe3ef7a9f68543d410a07dcdfed62de1ecdbe536467ac81a5bc8509b4ab790f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0960-894X(01)00652-7$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14118682$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11720860$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Willoughby, Christopher A</creatorcontrib><creatorcontrib>Berk, Scott C</creatorcontrib><creatorcontrib>Rosauer, Keith G</creatorcontrib><creatorcontrib>Degrado, Silvia</creatorcontrib><creatorcontrib>Chapman, Kevin T</creatorcontrib><creatorcontrib>Gould, Sandra L</creatorcontrib><creatorcontrib>Springer, Martin S</creatorcontrib><creatorcontrib>Malkowitz, Lorraine</creatorcontrib><creatorcontrib>Schleif, William A</creatorcontrib><creatorcontrib>Hazuda, Daria</creatorcontrib><creatorcontrib>Miller, Michael</creatorcontrib><creatorcontrib>Kessler, Joseph</creatorcontrib><creatorcontrib>Danzeisen, Renee</creatorcontrib><creatorcontrib>Holmes, Karen</creatorcontrib><creatorcontrib>Lineberger, Janet</creatorcontrib><creatorcontrib>Carella, Anthony</creatorcontrib><creatorcontrib>Carver, Gwen</creatorcontrib><creatorcontrib>Emini, Emilio A</creatorcontrib><title>Combinatorial synthesis of CCR5 antagonists</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Herein we report the preparation of a combinatorial library of compounds with potent CCR5 binding affinity. The library design was aided by SAR generated in a traditional medicinal chemistry effort. Compounds with novel combinations of subunits were discovered that have high binding affinity for the CCR5 receptor. A potent CCR5 antagonist from the library, compound
11 was found to have moderate anti-HIV-1 activity.
The synthesis of the combinatorial library of CCR5 antagonists is reported. Compound
2 was discovered, which has a 1
nM IC
50 in a CCR5 binding assay and inhibits HIV-1 replication with an IC
95 of 580
nM.</description><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>CCR5 Receptor Antagonists</subject><subject>Combinatorial Chemistry Techniques</subject><subject>HIV-1 - drug effects</subject><subject>Medical sciences</subject><subject>Pharmacology. 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The library design was aided by SAR generated in a traditional medicinal chemistry effort. Compounds with novel combinations of subunits were discovered that have high binding affinity for the CCR5 receptor. A potent CCR5 antagonist from the library, compound
11 was found to have moderate anti-HIV-1 activity.
The synthesis of the combinatorial library of CCR5 antagonists is reported. Compound
2 was discovered, which has a 1
nM IC
50 in a CCR5 binding assay and inhibits HIV-1 replication with an IC
95 of 580
nM.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>11720860</pmid><doi>10.1016/S0960-894X(01)00652-7</doi><tpages>5</tpages></addata></record> |
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| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences CCR5 Receptor Antagonists Combinatorial Chemistry Techniques HIV-1 - drug effects Medical sciences Pharmacology. Drug treatments Structure-Activity Relationship |
| title | Combinatorial synthesis of CCR5 antagonists |
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