Identification of a sulfonamide series of CCR2 antagonists.
A series of sulfonamide CCR2 antagonists was identified by high-throughput screening. Management of molecular weight and physical properties, in particular moderation of lipophilicity and study of pK(a), yielded highly potent CCR2 antagonists exhibiting good pharmacokinetic properties and improved potency in the presence of human plasma.
Peace
Simon
S
GlaxoSmithKline Medicines Research Centre, Stevenage, UK. Simon.2.Peace@gsk.com
Philp
Joanne
J
Brooks
Carl
C
Piercy
Val
V
Moores
Kitty
K
Smethurst
Chris
C
Watson
Steve
S
Gaines
Simon
S
Zippoli
Mara
M
Mookherjee
Claudette
C
Ife
Robert
R
D000818:Animals; D004305:Dose-Response Relationship, Drug; D057166:High-Throughput Screening Assays; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
D054389:Receptors, CCR1; D054390:Receptors, CCR2; D013449:Sulfonamides