- Studies on cyclin-dependent kinase inhibitors: Indolo-[2,3-a]pyrrolo[3,4-c]carbazoles versus bis-indolylmaleimides
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A series of indolo[2,3-a]pyrrolo[3,4-c]carbazoles and their bis-indolylmaleimides precursors have been prepared in order to compare their activity as D1-CDK4 inhibitors. Both enzymatic and antiproliferative assays have shown that the structurally more constrained indolo[2,3-a]pyrrolo[3,4-c]carbazoles are consistently more active (8-42-fold) in head-to-head comparison with their bis-indolylmaleimides counterparts. Cell-cycle analysis using flow cytometry have also shown that the indolocarbazoles are selective G1 blockers while the bis-indolylmaleimides arrest cells in the G2/M phase.
- Sanchez-Martinez, Concha,Shih, Chuan,Zhu, Guoxin,Li, Tiechao,Brooks, Harold B.,Patel, Bharvin K. R.,Schultz, Richard M.,DeHahn, Tammy B.,Spencer, Charles D.,Watkins, Scott A.,Ogg, Catherine A.,Considine, Eileen,Dempsey, Jack A.,Zhang, Faming
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p. 3841 - 3846
(2007/10/03)
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- Synthesis of bisindolylmaleimides
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The present invention provides for the reaction of optionally substituted indole-3-acetamides with optionally substituted methyl indole-3-glyoxyl reagent to prepare potent PKC inhibitors.
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- Design of new inhibitors for cdc2 kinase based on a multiple pseudosubstrate structure
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New inhibitors have been designed for cdc2 kinase based on a multiple pseudosubstrate structure. The new inhibitors have three different structural components: 3,4-bis(indol-3-yl)maleimide, Ac-Cys-(Ser)-Pro-Lys-Lys-NHMe, and ethyloxy group between the two components. Inhibitory activities toward cdc2 and other protein kinases were investigated, and the compound (21) with Ac- Cys-Pro-Lys-Lys-NHMe connected with the triethylene glycol spacer exhibited the most potent inhibition with relatively high selectivity.
- Sasaki, Shigeki,Hashimoto, Tomohiro,Obana, Norihiro,Yasuda, Hideyo,Uehara, Yoshimasa,Maeda, Minoru
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p. 1019 - 1022
(2007/10/03)
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- Synthesis of bisindolymaleimides
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The present invention provides for the reaction of optionally substituted indole-3-acetamides with optionally substituted methyl indole-3-glyoxyl reagent to prepare potent PKC inhibitors. The reaction is very efficient and robust macrocyclization methodology.
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- Bis-(1H-indol-3-YL)-maleinimide derivatives, processes for the preparation thereof and pharmaceutical compositions containing them
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The present invention provides bis-(1H-indol-3-yl)maleinimide derivatives and the pharmacologically acceptable salts thereof, processes for the preparation of these compounds, and pharmaceutical compositions containing them for the treatment of heart and blood vessel diseases, such as thromboses, arteriosclerosis, hypertension, of inflammatory processes, allergies, cancer, and certain degenerative damages of the central nervous system, as well as of diseases of the immune system and viral diseases.
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