1-Amido-1-phenyl-3-piperidinylbutanes - CCR5 antagonists for the treatment of HIV. Part 1.
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.
Barber
Christopher G
CG
Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. christopher.barber@pfizer.com
Blakemore
David C
DC
Chiva
Jean-Yves
JY
Eastwood
Rachel L
RL
Middleton
Donald S
DS
Paradowski
Kerry A
KA
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002073:Butanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D020650:Combinatorial Chemistry Techniques; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D015394:Molecular Structure; D010880:Piperidines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000737:chemistry
D019380:Anti-HIV Agents; D002073:Butanes; D065100:CCR5 Receptor Antagonists; D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D010880:Piperidines; D014326:Tropanes