title: Synthetic approaches to indolo[6,7-a]pyrrolo[3,4-c]carbazoles: potent cyclin D1/CDK4 inhibitors.
abstract: Synthesis of indolo[6,7-a]pyrrolo[3,4-c]carbazoles 1, a new class of cyclin D1/CDK4 inhibitors, by oxidation of the corresponding aryl indolylmaleimides 2, will be described. Two approaches to the synthesis of 2 were identified that required new methods for the synthesis of 7-substituted indole acetamides 3 and N-methyl (indol-7-yl)oxoacetates 6. The chemistry developed enabled introduction of functionality (-OR, NR(2)) at C(12) and N(13) facilitating structure-activity relationship (SAR) evaluation of this indolocarbazole platform.
authors.affiliation: Global Chemical Process Research and Development, Indianapolis, Indiana 46285, USA. mfaul@amgen.com
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Faul
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Engler
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Sullivan
authors.forename: John L
authors.initials: JL
authors.lastname: Grutsch
authors.forename: Marcella T
authors.initials: MT
authors.lastname: Clayton
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Martinelli
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Pawlak
authors.forename: Michael
authors.initials: M
authors.lastname: LeTourneau
authors.forename: D Scott
authors.initials: DS
authors.lastname: Coffey
authors.forename: Steven W
authors.initials: SW
authors.lastname: Pedersen
authors.forename: Stanley P
authors.initials: SP
authors.lastname: Kolis
authors.forename: Kelly
authors.initials: K
authors.lastname: Furness
authors.forename: Sushant
authors.initials: S
authors.lastname: Malhotra
authors.forename: Rima S
authors.initials: RS
authors.lastname: Al-awar
authors.forename: James E
authors.initials: JE
authors.lastname: Ray
mesh_terms: D000081:Acetamides / Q000737:chemistry; D000085:Acetates / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002227:Carbazoles / Q000138:chemical synthesis*; D019938:Cyclin D1 / Q000037:antagonists & inhibitors*; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D008301:Maleimides / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry; D010777:Photochemistry; D011518:Proto-Oncogene Proteins; D011758:Pyrroles / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D000085:Acetates; D000970:Antineoplastic Agents; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D016877:Oxidants; D011518:Proto-Oncogene Proteins; D011758:Pyrroles; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases