title: Identification of pyrrolo[2,3-g]indazoles as new Pim kinase inhibitors.
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.
authors.affiliation: Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, 63000 Clermont-Ferrand, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gavara
authors.forename: Virginie
authors.initials: V
authors.lastname: Suchaud
authors.forename: Lionel
authors.initials: L
authors.lastname: Nauton
authors.forename: Vincent
authors.initials: V
authors.lastname: Théry
authors.forename: Fabrice
authors.initials: F
authors.lastname: Anizon
authors.forename: Pascale
authors.initials: P
authors.lastname: Moreau
mesh_terms: D018360:Crystallography, X-Ray; D007191:Indazoles / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim