title: Hit-to-lead studies: the discovery of potent, orally active, thiophenecarboxamide IKK-2 inhibitors.
abstract: A hit-to-lead optimisation programme was carried out on the thiophenecarboxamide high throughput screening hits 1 and 2 resulting in the discovery of the potent and orally bioavailable IKK-2 inhibitor 22.
authors.affiliation: AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK. andrew.jg.baxter@astrazeneca.com
authors.forename: Andrew
authors.initials: A
authors.lastname: Baxter
authors.forename: Steve
authors.initials: S
authors.lastname: Brough
authors.forename: Anne
authors.initials: A
authors.lastname: Cooper
authors.forename: Eike
authors.initials: E
authors.lastname: Floettmann
authors.forename: Steve
authors.initials: S
authors.lastname: Foster
authors.forename: Christine
authors.initials: C
authors.lastname: Harding
authors.forename: Jason
authors.initials: J
authors.lastname: Kettle
authors.forename: Tom
authors.initials: T
authors.lastname: McInally
authors.forename: Craig
authors.initials: C
authors.lastname: Martin
authors.forename: Michelle
authors.initials: M
authors.lastname: Mobbs
authors.forename: Maurice
authors.initials: M
authors.lastname: Needham
authors.forename: Pete
authors.initials: P
authors.lastname: Newham
authors.forename: Stuart
authors.initials: S
authors.lastname: Paine
authors.forename: Steve
authors.initials: S
authors.lastname: St-Gallay
authors.forename: Sylvia
authors.initials: S
authors.lastname: Salter
authors.forename: John
authors.initials: J
authors.lastname: Unitt
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Xue
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D051550:I-kappa B Kinase; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D040081:Protein Array Analysis; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D008024:Ligands; D013876:Thiophenes; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human