The design and discovery of novel amide CCR5 antagonists.
The synthesis of a range of novel amine-containing structures and their primary potency as inhibitors of HIV-1 fusion via blocking of the CCR5 receptor is described. The development of the medicinal chemistry strategy and SAR's which led to the identification of the piperidine amide compounds 33 and 36 as excellent leads for further evaluation is described, along with key physicochemical data which highlighted their lead potential.
Pryde
David C
DC
Department of Chemistry, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. David.Pryde@pfizer.com
Corless
Martin
M
Fenwick
David R
DR
Mason
Helen J
HJ
Stammen
Blanda C
BC
Stephenson
Peter T
PT
Ellis
David
D
Bachelor
David
D
Gordon
David
D
Barber
Christopher G
CG
Wood
Anthony
A
Middleton
Donald S
DS
Blakemore
David C
DC
Parsons
Gemma C
GC
Eastwood
Rachel
R
Platts
Michelle Y
MY
Statham
Keith
K
Paradowski
Kerry A
KA
Burt
Catherine
C
Klute
Wolfgang
W
D000577:Amides / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D055808:Drug Discovery; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000577:Amides; D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D010880:Piperidines