title: Use of copper(I) catalyzed azide alkyne cycloaddition (CuAAC) for the preparation of conjugated pyrrolo[2,3-a]carbazole Pim kinase inhibitors.
abstract: We have previously demonstrated that 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 of new pyrrolocarbazoles substituted at the N-10 position. When their ability to inhibit Pim kinase activities were evaluated in in vitro assays, we observed that this nitrogen atom can be substituted without loss of Pim-1 and Pim-3 inhibitory potencies. Moreover, when we added a fluorescent dansyl group (compound 13), we were able to show that 13 penetrates the plasma membrane and enters the cytoplasm.
authors.affiliation: Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, 63000 Clermont-Ferrand, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Letribot
authors.forename: Rufine
authors.initials: R
authors.lastname: Akué-Gédu
authors.forename: Niina M
authors.initials: NM
authors.lastname: Santio
authors.forename: Malika
authors.initials: M
authors.lastname: El-Ghozzi
authors.forename: Daniel
authors.initials: D
authors.lastname: Avignant
authors.forename: Federico
authors.initials: F
authors.lastname: Cisnetti
authors.forename: Päivi J
authors.initials: PJ
authors.lastname: Koskinen
authors.forename: Arnaud
authors.initials: A
authors.lastname: Gautier
authors.forename: Fabrice
authors.initials: F
authors.lastname: Anizon
authors.forename: Pascale
authors.initials: P
authors.lastname: Moreau
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D002227:Carbazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D002462:Cell Membrane / Q000378:metabolism; D003300:Copper / Q000494:pharmacology*; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008297:Male; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013347:Subcellular Fractions; D014407:Tumor Cells, Cultured
chemical_list: D000480:Alkynes; D001386:Azides; D002227:Carbazoles; D047428:Protein Kinase Inhibitors; D003300:Copper; D051573:Proto-Oncogene Proteins c-pim-1