title: Synthesis of pyrazolo[4,3-a]phenanthridines, a new scaffold for Pim kinase inhibition.
abstract: A new series of nitro or amino substituted pyrazolo[4,3-a]phenanthridines was synthesized in 6 steps from 5-bromo-6-nitroindazole. The evaluation of their inhibitory potency toward Pim kinases demonstrated that the nitro series could be considered as an interesting starting point for the development of new Pim kinase inhibitors, especially Pim-3. A preferential binding mode was suggested by molecular modeling experiments for nitro series and Pim-1/Pim-3 ATP-binding sites. Moreover, the most active compounds exhibited antiproliferative activities toward PC3 cells in the micromolar range.
authors.affiliation: Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, 63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, BP 80026, 63171 Aubière, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Suchaud
authors.affiliation: Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, 63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, BP 80026, 63171 Aubière, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gavara
authors.affiliation: Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, 63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, BP 80026, 63171 Aubière, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Giraud
authors.affiliation: Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, 63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, BP 80026, 63171 Aubière, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Nauton
authors.affiliation: Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, 63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, BP 80026, 63171 Aubière, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Théry
authors.affiliation: Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, 63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, BP 80026, 63171 Aubière, France. Electronic address: Fabrice.ANIZON@univ-bpclermont.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Anizon
authors.affiliation: Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, 63000 Clermont-Ferrand, France; CNRS, UMR 6296, ICCF, BP 80026, 63171 Aubière, France. Electronic address: Pascale.MOREAU@univ-bpclermont.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Moreau
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010617:Phenanthridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010617:Phenanthridines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim
keywords: In vitro antiproliferative activities; Kinase inhibitors; Pim kinases; Pyrazolo[4,3-a]phenanthridines