title: Synthesis of anilino-monoindolylmaleimides as potent and selective PKCbeta inhibitors.
abstract: We report herein synthesis of PKCbeta-selective inhibitors possessing the novel pharmacophore of anilino-monoindolylmaleimide. Several compounds of this series exhibited IC50's as low as 50 nM against human PKCbeta2. One of the most potent compounds, 6l, inhibited PKCbeta1 and PKCbeta2 with IC50 of 21 and 5 nM, respectively, and exhibited selectivity of more than 60-fold in favor of PKCbeta2 relative to other PKC isozymes (PKCalpha, PKCgamma, and PKCepsilon).
authors.affiliation: Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tanaka
authors.forename: Shoichi
authors.initials: S
authors.lastname: Sagawa
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Hoshi
authors.forename: Fumito
authors.initials: F
authors.lastname: Shimoma
authors.forename: Isamu
authors.initials: I
authors.lastname: Matsuda
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakoda
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sasase
authors.forename: Masanori
authors.initials: M
authors.lastname: Shindo
authors.forename: Takashi
authors.initials: T
authors.lastname: Inaba
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D008301:Maleimides / Q000138:chemical synthesis* / Q000737:chemistry; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000737:chemistry; D064546:Protein Kinase C beta; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D011493:Protein Kinase C; D064546:Protein Kinase C beta