title: Design, synthesis, and evaluation of novel 3-amino-4-hydrazine-cyclobut-3-ene-1,2-diones as potent and selective CXCR2 chemokine receptor antagonists.
abstract: 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.
authors.affiliation: WuXi PharmaTech Co. Ltd, 288 FuTe Zhong Road, No. 1 Building, WaiGaoQiao Free Trade Zone, Shanghai 200131, PR China.
authors.forename: Shilan
authors.initials: S
authors.lastname: Liu
authors.forename: Yinhui
authors.initials: Y
authors.lastname: Liu
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wang
authors.forename: Yili
authors.initials: Y
authors.lastname: Ding
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Jingchao
authors.initials: J
authors.lastname: Dong
authors.forename: Angela
authors.initials: A
authors.lastname: Wong
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Chen
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Manuel
authors.initials: M
authors.lastname: Chan
authors.forename: Nicole
authors.initials: N
authors.lastname: Sawyer
authors.forename: Francois G
authors.initials: FG
authors.lastname: Gervais
authors.forename: Martin
authors.initials: M
authors.lastname: Henault
authors.forename: Stacia
authors.initials: S
authors.lastname: Kargman
authors.forename: Leanne L
authors.initials: LL
authors.lastname: Bedard
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Han
authors.forename: Rick
authors.initials: R
authors.lastname: Friesen
authors.forename: Robert B
authors.initials: RB
authors.lastname: Lobell
authors.forename: David M
authors.initials: DM
authors.lastname: Stout
mesh_terms: 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
chemical_list: D000893:Anti-Inflammatory Agents; D006834:Hydrazines; D016209:Interleukin-8; D023063:Receptors, Interleukin-8B