Synthesis and structure-activity relationships of new disubstituted phenyl-containing 3,4-diamino-3-cyclobutene-1,2-diones as CXCR2 receptor antagonists.
A series of 3,4- and 3,5-disubstituted phenyl-containing cyclobutenedione analogues were synthesized and evaluated as CXCR2 receptor antagonists. Variations in the disubstitution pattern of the phenyl ring afforded new compounds with potent CXCR2 binding affinity in the low nanomolar ranges. Moreover, two potent compounds 19 and 26 exhibited good oral pharmacokinetic profiles.
Lai
Gaifa
G
Pharmacopeia, Inc., 3000 Eastpark Boulevard, Cranbury, NJ 08512, USA. galai@pcop.com
Merritt
J Robert
JR
He
Zhenmin
Z
Feng
Daming
D
Chao
Jianhua
J
Czarniecki
Michael F
MF
Rokosz
Laura L
LL
Stauffer
Tara M
TM
Rindgen
Diane
D
Taveras
Arthur G
AG
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003503:Cyclobutanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000882:Haplorhini; D015394:Molecular Structure; D011485:Protein Binding; D051381:Rats; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D003503:Cyclobutanes; D023063:Receptors, Interleukin-8B