title: Synthesis and biological activities of 4-substituted pyrrolo[2,3-a]carbazole Pim kinase inhibitors.
abstract: Pyrrolo[2,3-a]carbazole-3-carbaldehydes are potent Pim kinase inhibitors with in vitro antiproliferative activities. In the present study, we report the synthesis and biological activities (Pim kinase inhibition and in vitro antiproliferative potency) of new 4-substituted pyrrolo[2,3-a]carbazoles. The results demonstrated that the Pim kinase inhibitory potency (especially Pim-3) can be conserved for pyrrolo[2,3-a]carbazoles bearing a methoxycarbonyl group at the 4-position without a formyl at the 3-position. Moreover, compound 27 that was found to be active against Pim-1 and Pim-3 kinases showed antiproliferative activities in the micromolar range.
authors.affiliation: Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Giraud
authors.forename: Rufine
authors.initials: R
authors.lastname: Akué-Gédu
authors.forename: Lionel
authors.initials: L
authors.lastname: Nauton
authors.forename: Nicolas
authors.initials: N
authors.lastname: Candelon
authors.forename: Eric
authors.initials: E
authors.lastname: Debiton
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: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim