title: First generation 5-vinyl-3-pyridinecarbonitrile PKCtheta inhibitors.
abstract: A series of 5-vinyl-3-pyridinecarbonitriles were synthesized and evaluated as PKCtheta inhibitors. The systematic optimization of 4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-phenylvinyl]-3-pyridinecarbonitrile 3 resulted in the identification of compound 23e as a potent PKCtheta inhibitor with good selectivity over PKCdelta.
authors.affiliation: Wyeth Research, Chemical Sciences, 401 N. Middletown Road, Pearl River, NY 10965, USA. niuc@wyeth.com
authors.forename: Chuansheng
authors.initials: C
authors.lastname: Niu
authors.forename: Diane H
authors.initials: DH
authors.lastname: Boschelli
authors.forename: L Nathan
authors.initials: LN
authors.lastname: Tumey
authors.forename: Niala
authors.initials: N
authors.lastname: Bhagirath
authors.forename: Joan
authors.initials: J
authors.lastname: Subrath
authors.forename: Jaechul
authors.initials: J
authors.lastname: Shim
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Biqi
authors.initials: B
authors.lastname: Wu
authors.forename: Clark
authors.initials: C
authors.lastname: Eid
authors.forename: Julie
authors.initials: J
authors.lastname: Lee
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Yang
authors.forename: Agnes
authors.initials: A
authors.lastname: Brennan
authors.forename: Divya
authors.initials: D
authors.lastname: Chaudhary
mesh_terms: D000818:Animals; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D000074121:Protein Kinase C-theta; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D007527:Isoenzymes; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D000074121:Protein Kinase C-theta