Synthesis and structure-activity relationship of 2-amino-3-heteroaryl-quinoxalines as non-peptide, small-molecule antagonists for interleukin-8 receptor.
Interleukin-8 modulation is implicated in many inflammatory and cancer diseases. Starting from a mass-screening hit, the synthesis and structure-activity relationship of 2-amino-3-heteroarylquinoxalines as non-peptide, small molecule interleukine-8 receptor antagonists have been developed. The optimized derivatives, PD 0210293 (13y) and PD 0220245 (13r), show inhibition of both IL-8 receptor binding and IL-8-mediated neutrophil chemotaxis.
Li
Jie Jack
JJ
Chemistry Department, Pfizer Global R&D, 2800 Plymouth Rd., Ann Arbor, MI 48105, USA. jack.li@pfizer.com
Carson
Kenneth G
KG
Trivedi
Bharat K
BK
Yue
Wen Song
WS
Ye
Qing
Q
Glynn
Roberta A
RA
Miller
Steven R
SR
Connor
David T
DT
Roth
Bruce D
BD
Luly
Jay R
JR
Low
Joseph E
JE
Heilig
David J
DJ
Yang
Weixing
W
Qin
Shixin
S
Hunt
Stephen
S
D000893:Anti-Inflammatory Agents / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D003959:Diamines; D011810:Quinoxalines; D023062:Receptors, Interleukin-8A; D002118:Calcium