Modulators of the human CCR5 receptor. Part 3: SAR of substituted 1-[3-(4-methanesulfonylphenyl)-3-phenylpropyl]-piperidinyl phenylacetamides.
SAR and PK studies led to the identification of N-(1-{(3R)-3-(3,5-difluorophenyl)-3-[4-methanesulfonylphenyl] propyl}piperidin-4-yl)-N-ethyl-2-[4-methanesulfonylphenyl]acetamide as a highly potent and selective ligand for the human CCR5 chemokine receptor with good oral pharmacokinetic properties.
Cumming
John G
JG
Respiratory and Inflammation Research Area, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. john.cumming@astrzeneca.com
Brown
Simon J
SJ
Cooper
Anne E
AE
Faull
Alan W
AW
Flynn
Anthony P
AP
Grime
Ken
K
Oldfield
John
J
Shaw
John S
JS
Shepherd
Emma
E
Tucker
Howard
H
Whittaker
David
D
D000083:Acetanilides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D000818:Animals; D065100:CCR5 Receptor Antagonists; D018360:Crystallography, X-Ray; D004285:Dogs; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013997:Time Factors
D000083:Acetanilides; D065100:CCR5 Receptor Antagonists; D010880:Piperidines; D013450:Sulfones