Evaluation of amide replacements in CCR5 antagonists as a means to increase intrinsic permeability. Part 2: SAR optimization and pharmacokinetic profile of a homologous azacyle series
In our CCR5 program, piperidine and azetidine amide replacements as means to improve intrinsic permeability were evaluated. This led to new series of potent CCR5 antagonists, with improved PK behavior. Replacement of a secondary amide with a piperidine or azetidine moiety in a series of CCR5 antagon...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2010-11, Vol.20 (22), p.6802-6807 |
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| container_issue | 22 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 20 |
| creator | Wanner, Jutta Chen, Lijing Lemoine, Rémy C. Kondru, Rama Jekle, Andreas Heilek, Gabrielle deRosier, André Ji, Changhua Berry, Pamela W. Rotstein, David M. |
| description | In our CCR5 program, piperidine and azetidine amide replacements as means to improve intrinsic permeability were evaluated. This led to new series of potent CCR5 antagonists, with improved PK behavior.
Replacement of a secondary amide with a piperidine or azetidine moiety in a series of CCR5 antagonists led to the discovery of compounds with increased intrinsic permeability. This effort led to the identification of a potent CCR5 antagonist which exhibited an improved in vivo pharmacokinetic profile. |
| doi_str_mv | 10.1016/j.bmcl.2010.08.118 |
| format | Article |
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Replacement of a secondary amide with a piperidine or azetidine moiety in a series of CCR5 antagonists led to the discovery of compounds with increased intrinsic permeability. This effort led to the identification of a potent CCR5 antagonist which exhibited an improved in vivo pharmacokinetic profile.</description><subject>Amides - chemistry</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Aza Compounds - chemistry</subject><subject>Aza Compounds - pharmacokinetics</subject><subject>Aza Compounds - pharmacology</subject><subject>Biological and medical sciences</subject><subject>CCR5 antagonist</subject><subject>CCR5 Receptor Antagonists</subject><subject>HIV entry inhibition</subject><subject>Medical sciences</subject><subject>Permeability</subject><subject>Pharmacology. 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Part 2: SAR optimization and pharmacokinetic profile of a homologous azacyle series</title><author>Wanner, Jutta ; Chen, Lijing ; Lemoine, Rémy C. ; Kondru, Rama ; Jekle, Andreas ; Heilek, Gabrielle ; deRosier, André ; Ji, Changhua ; Berry, Pamela W. ; Rotstein, David M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-2f9a06579f84f318e69ddfdba0abb675c5f089b569ddbb2319c336b68a4c3d793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Amides - chemistry</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Aza Compounds - chemistry</topic><topic>Aza Compounds - pharmacokinetics</topic><topic>Aza Compounds - pharmacology</topic><topic>Biological and medical sciences</topic><topic>CCR5 antagonist</topic><topic>CCR5 Receptor Antagonists</topic><topic>HIV entry inhibition</topic><topic>Medical sciences</topic><topic>Permeability</topic><topic>Pharmacology. 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Part 2: SAR optimization and pharmacokinetic profile of a homologous azacyle series</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2010-11-15</date><risdate>2010</risdate><volume>20</volume><issue>22</issue><spage>6802</spage><epage>6807</epage><pages>6802-6807</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>In our CCR5 program, piperidine and azetidine amide replacements as means to improve intrinsic permeability were evaluated. This led to new series of potent CCR5 antagonists, with improved PK behavior.
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Amides - chemistry Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Aza Compounds - chemistry Aza Compounds - pharmacokinetics Aza Compounds - pharmacology Biological and medical sciences CCR5 antagonist CCR5 Receptor Antagonists HIV entry inhibition Medical sciences Permeability Pharmacology. Drug treatments Structure-Activity Relationship |
| title | Evaluation of amide replacements in CCR5 antagonists as a means to increase intrinsic permeability. Part 2: SAR optimization and pharmacokinetic profile of a homologous azacyle series |
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