Design, synthesis, and evaluation of novel 3-amino-4-hydrazine-cyclobut-3-ene-1,2-diones as potent and selective CXCR2 chemokine receptor antagonists.
We describe herein a novel series of 3-amino-4-hydrazine-cyclobut-3-ene-1,2-diones as potent and selective inhibitors against the CXCR2 chemokine receptor and IL-8-mediated chemotaxis of a CXCR2-expressing cell line. Furthermore, these alkyl-hydrazine series inhibitors such as 5b demonstrated acceptable metabolic stability when incubated in human and rat microsomes.
Liu
Shilan
S
WuXi PharmaTech Co. Ltd, 288 FuTe Zhong Road, No. 1 Building, WaiGaoQiao Free Trade Zone, Shanghai 200131, PR China.
Liu
Yinhui
Y
Wang
Hongmei
H
Ding
Yili
Y
Wu
Hao
H
Dong
Jingchao
J
Wong
Angela
A
Chen
Shu-Hui
SH
Li
Ge
G
Chan
Manuel
M
Sawyer
Nicole
N
Gervais
Francois G
FG
Henault
Martin
M
Kargman
Stacia
S
Bedard
Leanne L
LL
Han
Yongxin
Y
Friesen
Rick
R
Lobell
Robert B
RB
Stout
David M
DM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D002633:Chemotaxis / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D006834:Hydrazines; D016209:Interleukin-8; D023063:Receptors, Interleukin-8B