title: The design and discovery of novel amide CCR5 antagonists.
abstract: 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.
authors.affiliation: Department of Chemistry, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. David.Pryde@pfizer.com
authors.forename: David C
authors.initials: DC
authors.lastname: Pryde
authors.forename: Martin
authors.initials: M
authors.lastname: Corless
authors.forename: David R
authors.initials: DR
authors.lastname: Fenwick
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Mason
authors.forename: Blanda C
authors.initials: BC
authors.lastname: Stammen
authors.forename: Peter T
authors.initials: PT
authors.lastname: Stephenson
authors.forename: David
authors.initials: D
authors.lastname: Ellis
authors.forename: David
authors.initials: D
authors.lastname: Bachelor
authors.forename: David
authors.initials: D
authors.lastname: Gordon
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Barber
authors.forename: Anthony
authors.initials: A
authors.lastname: Wood
authors.forename: Donald S
authors.initials: DS
authors.lastname: Middleton
authors.forename: David C
authors.initials: DC
authors.lastname: Blakemore
authors.forename: Gemma C
authors.initials: GC
authors.lastname: Parsons
authors.forename: Rachel
authors.initials: R
authors.lastname: Eastwood
authors.forename: Michelle Y
authors.initials: MY
authors.lastname: Platts
authors.forename: Keith
authors.initials: K
authors.lastname: Statham
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Paradowski
authors.forename: Catherine
authors.initials: C
authors.lastname: Burt
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Klute
mesh_terms: 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
chemical_list: D000577:Amides; D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D010880:Piperidines