Synthesis of anilino-monoindolylmaleimides as potent and selective PKCbeta inhibitors

Masahiro Tanaka; Shoichi Sagawa; Jun-ichi Hoshi; Fumito Shimoma; Isamu Matsuda; Kenji Sakoda; Tomohiko Sasase; Masanori Shindo; Takashi Inaba

doi:10.1016/j.bmcl.2004.07.061

Synthesis of anilino-monoindolylmaleimides as potent and selective PKCbeta inhibitors

Bioorg Med Chem Lett. 2004 Oct 18;14(20):5171-4. doi: 10.1016/j.bmcl.2004.07.061.

Authors

Masahiro Tanaka¹, Shoichi Sagawa, Jun-ichi Hoshi, Fumito Shimoma, Isamu Matsuda, Kenji Sakoda, Tomohiko Sasase, Masanori Shindo, Takashi Inaba

Affiliation

¹ Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.

PMID: 15380221
DOI: 10.1016/j.bmcl.2004.07.061

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).

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Aniline Compounds / chemical synthesis*
Aniline Compounds / chemistry
Humans
Indoles / chemical synthesis*
Indoles / chemistry
Isoenzymes / antagonists & inhibitors
Isoenzymes / chemistry
Maleimides / chemical synthesis*
Maleimides / chemistry
Protein Kinase C / antagonists & inhibitors*
Protein Kinase C / chemistry
Protein Kinase C beta
Structure-Activity Relationship

Substances

Aniline Compounds
Indoles
Isoenzymes
Maleimides
Protein Kinase C
Protein Kinase C beta