Synthetic Approaches to Indolo[6,7-a]pyrrolo[3,4-c]carbazoles:  Potent Cyclin D1/CDK4 Inhibitors

Synthetic Approaches to Indolo[6,7-a]pyrrolo[3,4-c]carbazoles:  Potent Cyclin D1/CDK4 Inhibitors

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 acet...

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Veröffentlicht in:Journal of organic chemistry 2004-04, Vol.69 (9), p.2967-2975
Hauptverfasser: Faul, Margaret M, Engler, Thomas A, Sullivan, Kevin A, Grutsch, John L, Clayton, Marcella T, Martinelli, Michael J, Pawlak, Joseph M, LeTourneau, Michael, Coffey, D. Scott, Pedersen, Steven W, Kolis, Stanley P, Furness, Kelly, Malhotra, Sushant, Al-awar, Rima S, Ray, James E
Format: Artikel
Sprache:eng
Schlagworte:
Acetamides - chemistry
Acetates - chemistry
Antineoplastic Agents - chemical synthesis
Carbazoles - chemical synthesis
Chemistry
Cyclin D1 - antagonists & inhibitors
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinases - antagonists & inhibitors
Enzyme Inhibitors - chemical synthesis
Exact sciences and technology
Heterocyclic compounds
Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings
Humans
Indoles - chemistry
Maleimides - chemistry
Organic chemistry
Oxidants - chemistry
Photochemistry
Preparations and properties
Proto-Oncogene Proteins
Pyrroles - chemistry
Structure-Activity Relationship
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Zusammenfassung: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, NR2) at C12 and N13 facilitating structure−activity relationship (SAR) evaluation of this indolocarbazole platform.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo035606v