Abstract
The synthesis, SAR and biological evaluation of symmetrical amide analogues of our clinical candidate SCH 351125 are described. A series of potent and orally bioavailable CCR5 antagonists containing symmetrical 2,6-dimethyl isonicotinamides and 2, 6-dimethyl pyrimidines amides were generated with enhanced affinity for the CCR5 receptor.
MeSH terms
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Amides / chemical synthesis*
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Amides / pharmacokinetics
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Amides / pharmacology
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Animals
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / pharmacokinetics
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Anti-HIV Agents / pharmacology
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CCR5 Receptor Antagonists*
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Chemokine CCL5 / antagonists & inhibitors
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Cyclic N-Oxides
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Drug Evaluation, Preclinical
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HIV-1 / drug effects
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Heterocyclic Compounds, 3-Ring / chemical synthesis*
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Heterocyclic Compounds, 3-Ring / pharmacokinetics
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Heterocyclic Compounds, 3-Ring / pharmacology
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Humans
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Inhibitory Concentration 50
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Oximes
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Piperidines / chemical synthesis*
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Piperidines / pharmacokinetics
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Piperidines / pharmacology
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Pyridines
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Rats
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Structure-Activity Relationship
Substances
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Amides
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Anti-HIV Agents
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CCR5 Receptor Antagonists
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Chemokine CCL5
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Cyclic N-Oxides
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Heterocyclic Compounds, 3-Ring
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Oximes
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Piperidines
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Pyridines
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Ancriviroc