Design, synthesis, and evaluation of naphthalene-sulfonamide antagonists of human CCR8.
The design, synthesis, and structure-activity relationship development of naphthalene-derived human CCR8 antagonists is described. In vitro binding assay results of these investigations are reported, critical interactions of the antagonists with CCR8 are defined, and preliminary physicochemical and pharmacokinetic data for the naphthalene scaffold are presented.
Jenkins
Tracy J
TJ
Department of Medicinal Chemistry, Department of Pharmacology, and Drug Safety and Disposition, Millennium Pharmaceuticals, 40 Landsdowne Street, Cambridge, Massachusetts 02139, USA. tracy.jenkins@biogenidec.com
Guan
Bing
B
Dai
Mingshi
M
Li
Gang
G
Lightburn
Thomas E
TE
Huang
Shan
S
Freeze
B Scott
BS
Burdi
Douglas F
DF
Jacutin-Porte
Swanee
S
Bennett
Robert
R
Chen
Weirong
W
Minor
Charles
C
Ghosh
Shomir
S
Blackburn
Christopher
C
Gigstad
Kenneth M
KM
Jones
Matthew
M
Kolbeck
Roland
R
Yin
Wei
W
Smith
Sean
S
Cardillo
Daniel
D
Ocain
Timothy D
TD
Harriman
Geraldine C
GC
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
C103330:CCR8 protein, human; D009281:Naphthalenes; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D013449:Sulfonamides; D002118:Calcium