title: Inhibition of IKK-2 by 2-[(aminocarbonyl)amino]-5-acetylenyl-3-thiophenecarboxamides.
abstract: A series of 21 novel 2-[(aminocarbonyl)amino]-5-acetylenyl-3-thiophenecarboxamides were synthesized and evaluated for the inhibition of IKK-2. In spite of their often modest activity on the enzyme, six selected analogs showed significant inhibition of the production of inflammatory cytokine IL-8 in IL-1beta stimulated rheumatoid arthritis-derived synovial fibroblasts, demonstrating their potential usefulness as NF-kappaB regulators.
authors.affiliation: Department of Medicinal Chemistry, Pfizer Inc., St Louis, MO 63017, USA. bonafoux@biogenidec.com
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonafoux
authors.forename: Sheri
authors.initials: S
authors.lastname: Bonar
authors.forename: Lori
authors.initials: L
authors.lastname: Christine
authors.forename: Michael
authors.initials: M
authors.lastname: Clare
authors.forename: Ann
authors.initials: A
authors.lastname: Donnelly
authors.forename: Julia
authors.initials: J
authors.lastname: Guzova
authors.forename: Nandini
authors.initials: N
authors.lastname: Kishore
authors.forename: Patrick
authors.initials: P
authors.lastname: Lennon
authors.forename: Adam
authors.initials: A
authors.lastname: Libby
authors.forename: Sumathy
authors.initials: S
authors.lastname: Mathialagan
authors.forename: William
authors.initials: W
authors.lastname: McGhee
authors.forename: Sharon
authors.initials: S
authors.lastname: Rouw
authors.forename: Cindy
authors.initials: C
authors.lastname: Sommers
authors.forename: Michael
authors.initials: M
authors.lastname: Tollefson
authors.forename: Catherine
authors.initials: C
authors.lastname: Tripp
authors.forename: Richard
authors.initials: R
authors.lastname: Weier
authors.forename: Serge
authors.initials: S
authors.lastname: Wolfson
authors.forename: Yao
authors.initials: Y
authors.lastname: Min
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016209:Interleukin-8; D013876:Thiophenes; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human