1-Amido-1-phenyl-3-piperidinylbutanes — CCR5 antagonists for the treatment of HIV. Part 1

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 4; pp. 1075 - 1079
• Main Authors: Barber, Christopher G., Blakemore, David C., Chiva, Jean-Yves, Eastwood, Rachel L., Middleton, Donald S., Paradowski, Kerry A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.02.2009
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Antagonist; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Antiviral; Butanes - chemical synthesis; Butanes - chemistry; Butanes - pharmacology; CCR5; CCR5 Receptor Antagonists; Combinatorial Chemistry Techniques; Ether-A-Go-Go Potassium Channels - drug effects; HIV; HIV - drug effects; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Molecular Structure; Piperidines - pharmacology; Structure-Activity Relationship; Tropanes - chemistry; Antiviral; Antagonist; HIV; CCR5
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.01.009

The development of a new class of CCR5 antagonist replacing the tropane core of maraviroc by piperidine with a branched N-substituent is described. Compound 15h shows good whole cell antiviral activity together with microsomal stability and only weak activity at the hERG ion channel. The development of a new class of CCR5 antagonist replacing the tropane core of maraviroc by piperidine with a branched N-substituent is described. Compound 15h shows good whole cell antiviral activity together with microsomal stability and only weak activity at the hERG ion channel.