Identification of pyrrolo[2,3-g]indazoles as new Pim kinase inhibitors

Laurent Gavara; Virginie Suchaud; Lionel Nauton; Vincent Théry; Fabrice Anizon; Pascale Moreau

doi:10.1016/j.bmcl.2013.02.074

Identification of pyrrolo[2,3-g]indazoles as new Pim kinase inhibitors

Bioorg Med Chem Lett. 2013 Apr 15;23(8):2298-301. doi: 10.1016/j.bmcl.2013.02.074. Epub 2013 Feb 26.

Authors

Laurent Gavara¹, Virginie Suchaud, Lionel Nauton, Vincent Théry, Fabrice Anizon, Pascale Moreau

Affiliation

¹ Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, 63000 Clermont-Ferrand, France.

PMID: 23499503
DOI: 10.1016/j.bmcl.2013.02.074

Abstract

The synthesis and Pim kinase inhibition potency of a new series of pyrrolo[2,3-g]indazole derivatives is described. The results obtained in this preliminary structure-activity relationship study pointed out that sub-micromolar Pim-1 and Pim-3 inhibitory potencies could be obtained in this series, more particularly for compounds 10 and 20, showing that pyrrolo[2,3-g]indazole scaffold could be used for the development of new potent Pim kinase inhibitors. Molecular modeling experiments were also performed to study the binding mode of these compounds in Pim-3 ATP-binding pocket.

Publication types

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

MeSH terms

Crystallography, X-Ray
Indazoles / chemistry*
Indazoles / pharmacology*
Models, Molecular
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology*
Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
Proto-Oncogene Proteins c-pim-1 / chemistry
Pyrroles / chemistry*
Pyrroles / pharmacology*
Structure-Activity Relationship

Substances

Indazoles
Protein Kinase Inhibitors
Pyrroles
Proto-Oncogene Proteins c-pim-1
proto-oncogene proteins pim