- Synthesis and cytotoxic activities of a series of novel N -methyl-bisindolylmaleimide amide derivatives
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A novel series of N-methyl-bisindolylmaleimides were synthesized and evaluated for their inhibitory activities against nine tumor cell lines. Some of the compounds showed an interesting activity against the tested cell lines. The most potent compounds 5e
- Wang, Ke,Liu, Zhan-Zhu
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- Synthesis and properties of novel heat-resistant fluorescent conjugated polymers with bisindolylmaleimide
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Conjugated polymers with bisindolylmaleimide (BIM) backbone are obtained by the condensation polymerization of methyl and octanyl N-substituted BIMs with 4,4'-difluoro-diphenylsulfone and 4,4'-difluoro-diphenylketone. The structures of polymers are confirmed by FTIR and NMR spectroscopy. The polymers exhibit both high glass transition temperatures (Tg > 175 °C) and high decomposition temperatures (T5 > 395 °C). Meanwhile, The UV–vis absorption and fluorescence spectra of the polymers are similar to the corresponding substituted BIMs. The quantum chemistry calculations indicate that the first excited states of polymers are mostly contributed by BIM structures.
- Zhang, Qianfeng,Chang, Guanjun,Zhang, Lin
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- New synthesis of KT5823 indolocarbazole aglycone
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The indolo[2,3-α]pyrrolo[3,4-c]carbazole aglycone of the selective protein kinase G inhibitor KT5823 has been synthesised in four steps and 36percent overall yield from 2,3-dichloro-N-methylmaleimide by utilising an efficient new two step reduction sequen
- Burtin, Guillaume E.,Madge, David J.,Selwood, David L.
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- Synthesis of arcyriarubin a and arcyriaflavin a via cross-coupling of indolylboronic acid with dibromomaleimides
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Arcyriarubin A was first isolated by Steglich in 1980; it is also the key intermediate in the synthesis of indolocarbazole compounds. A new synthetic approach to the natural products arcyriaflavin A and arcyriarubin A is described. The key step is a Suzuk
- Wang, Ke,Liu, Zhanzhu
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- Friedel-Crafts alkylation on indolocarbazoles catalyzed by two dimethylallyltryptophan synthases from Aspergillus
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Prenylated indolocarbazoles have been reported neither from natural sources, nor by chemical synthetic approaches. In this Letter, we report a regiospecific prenylation of indolocarbazoles at the para-position of the indole N-atom by two recombinant enzymes from the dimethylallyltryptophan synthase (DMATS) superfamily, that is, 5-DMATS from Aspergillus clavatus and FgaPT2 from Aspergillus fumigatus.
- Yu, Xia,Yang, Aigang,Lin, Wenhan,Li, Shu-Ming
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- Structure-activity relationship of N-methyl-bisindolylmaleimide derivatives as cell death inhibitors
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A series of N-methyl-bisindolylmaleimide derivatives was synthesized and evaluated as cell death inhibitors. N-Methyl-2-[1-(3-aminopropyl)-1H-indol-3-yl] -3-(1H-indol-3-yl)maleimide (21) was the most potent inhibitor of H 2O2-induced necrotic death of human leukemia HL60 cells among them.
- Katoh, Miho,Dodo, Kosuke,Fujita, Mikako,Sodeoka, Mikiko
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- Macrocyclic bisindolylmaleimides as inhibitors of protein kinase C and glycogen synthase kinase-3
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Efficient methods were developed to synthesize a novel series of macrocyclic bisindolylmaleimides containing linkers with multiple heteroatoms. Potent inhibitors (single digit nanomolar IC50) for PKC-β and GSK-3β were identified, and compounds showed good selectivity over PKC-α, -γ, -δ, -ε, and -ζ. Representative compound 5a also had high selectivity in a screening panel of 10 other protein kinases. In cell-based functional assays, several compounds effectively blocked interleukin-8 release induced by PKC-βII and increased glycogen synthase activity by inhibiting GSK-3β.
- Zhang, Han-Cheng,White, Kimberly B.,Ye, Hong,McComsey, David F.,Derian, Claudia K.,Addo, Michael F.,Andrade-Gordon, Patricia,Eckardt, Annette J.,Conway, Bruce R.,Westover, Lori,Xu, Jun Z.,Look, Richard,Demarest, Keith T.,Emanuel, Stuart,Maryanoff, Bruce E.
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- Synthesis and Characterization of the Selective, Reversible PKCβ Inhibitor (9 S)-9-[(Dimethylamino)methyl]-6,7,10,11-tetrahydro-9 H,18 H-5,21:12,17-dimethenodibenzo[ e,k]pyrrolo[3,4- h][1,4,13]oxadiazacyclohexadecine-18,20(19 H)-dione, Ruboxistaurin (LY333531)
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The demonstrated role of PKCβ in mediating amphetamine-stimulated dopamine efflux, which regulates amphetamine-induced dopamine transporter trafficking and activity, has promoted the research use of the selective, reversible PKCβ inhibitor (9S)-9-[(dimethylamino)methyl]-6,7,10,11-tetrahydro-9H,18H-5,21:12,17-dimethenodibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecine-18,20(19H)-dione, ruboxistaurin. Despite the interest in development of ruboxistaurin as the mesylate monohydrate (Arxxant) for the treatment of diabetic retinopathy, macular edema, and nephoropathy, several crucial details in physicochemical characterization were erroneous or missing. This report describes the synthesis and full characterization of ruboxistaurin free base (as a monohydrate), including X-ray crystallography to confirm the absolute configuration, and of the mesylate salt, isolated as a hydrate containing 1.5 mol of water per mole.
- Lewin, Anita H.,Brieaddy, Larry,Deschamps, Jeffrey R.,Imler, Gregory H.,Mascarella, S. Wayne,Reddy, P. Anantha,Carroll, F. Ivy
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p. 246 - 251
(2018/09/25)
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- 3. 4 - b (3 - indole) - 2, 5 - dione -3 - pyrroline imine compound and its preparation method and application
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The invention discloses a 3,4-bi(3-indole)-2,5-dione-3-pyrrolineimine compound, a preparation method of the compound and application of the compound in an anti-cancer drug. The key points of the technical scheme are that the 3,4-bi(3-indole)-2,5-dione-3-pyrrolineimine compound is prepared by taking an aldehyde compound R-CHO and 1-amino-3,4-bi(3-indole)-3-pyrroline-2,5-dione with the structural formula which is as shown in the specification as raw materials; and the general structural formula of the compound is as shown in the specification. The invention also discloses a method for preparing the 3,4-bi(3-indole)-2,5-dione-3-pyrrolineimine compound and application of the compound in the anti-cancer drug. According to the preparation method disclosed by the invention, the raw materials are low in price and readily available, the operation is simple, and the prepared 3,4-bi(3-indole)-2,5-dione-3-pyrrolineimine compound has high biological activity and has good application prospects in the preparation of anti-cancer drug compounds.
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Paragraph 0048; 0049; 0053; 0054
(2017/07/25)
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- With anticancer activity of 3, 4 - b (3 - indole) - 2, 5 - dione - 1 - pyrrole thiourea compound and its preparation method and application
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The invention discloses a 3,4-bi(3-benzpyrole)-2,5-dione-1-pyrroleimine thiourea compound with antitumor activity and a preparation method and application thereof. The technical scheme of the invention is characterized in that the 3,4-bi(3-benzpyrole)-2,5-dione-1-pyrroleimine thiourea compound with antitumor activity is prepared by taking a substituted isothiocyanate compound R-NCS and 1-amino-3,4-bi(3-benzpyrole)-3-pyrroline-2,5-dione shown in the specification as raw materials, and the structural general formula is shown in the specification. The invention further discloses the preparation method and the antitumor activity of the 3,4-bi(3-benzpyrole)-2,5-dione-1-pyrroleimine thiourea compound with antitumor activity. The preparation method disclosed by the invention has the advantages that the raw material is low in price and easily available, the operation is simple, and the prepared 3,4-bi(3-benzpyrole)-2,5-dione-1-pyrroleimine thiourea compound has better biological activity, and has better application prospect in preparation of antitumor medical compounds.
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Paragraph 0043; 0044; 0045; 0046; 0047; 0048; 0049; 0050
(2017/08/25)
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- Indolo[2, 3-a]pyrrole[3, 4-c]carbazole-5, 7-dione-6-arylhydrazone compound and its preparation method and use in anti-cancer drug
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The invention discloses an indolo[2, 3-a]pyrrole[3, 4-c]carbazole-5, 7-dione-6-arylhydrazone compound and its preparation method and use. The indolo[2, 3-a]pyrrole[3, 4-c]carbazole-5, 7-dione-6-arylhydrazone compound is prepared from an aldehyde compound R-CHO and 6-amino-indolo[2, 3-a]pyrrole[3, 4-c]carbazole-5, 7-dione as raw materials and has a general structural formula shown in the description. The invention also discloses a preparation method of the indolo[2, 3-a]pyrrole[3, 4-c]carbazole-5, 7-dione-6-arylhydrazone compound and a use of the indolo[2, 3-a]pyrrole[3, 4-c]carbazole-5, 7-dione-6-arylhydrazone compound in preparation of anti-cancer drugs. The preparation method has the advantages of easily available raw materials and simple processes. The indolo[2, 3-a]pyrrole[3, 4-c]carbazole-5, 7-dione-6-arylhydrazone compound has good biological activity and has a good application prospect in preparation of anti-cancer drug compounds.
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Paragraph 0057; 0061; 0062
(2017/08/28)
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- A double-indole maleic imide compound of preparation method
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The invention relates to a preparation method of bisindolyl maleimide compounds, which comprises the following steps: adding indole, maleimide compounds and zinc chloride into a solvent, heating under reflux for 10-24 hours, adding water, stirring, extrac
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Paragraph 0050-0051
(2017/10/31)
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- Indole [2,3-a] pyrrole[3,4-c] carbazole-5,7-diketone-6-thiosemicarbazone compounds with antitumor activity as well as preparation method and application of compounds
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The invention discloses indole [2,3-a] pyrrole[3,4-c] carbazole-5,7-diketone-6-thiosemicarbazone compounds with antitumor activity as well as a preparation method and an application of the compounds. The technical scheme is characterized in that the indole [2,3-a] pyrrole[3,4-c] carbazole-5,7-diketone-6-thiosemicarbazone compounds with the antitumor activity are prepared from raw materials including substituent isothiocyanate compounds R-NCS and 6-amino-indole [2,3-a] pyrrole[3,4-c] carbazole-5,7-diketone shown in the specification and has a general structure formula shown in the specification. The invention further discloses the preparation method of the indole [2,3-a] pyrrole[3,4-c] carbazole-5,7-diketone-6-thiosemicarbazone compounds with the antitumor activity and the application of the indole [2,3-a] pyrrole[3,4-c] carbazole-5,7-diketone-6-thiosemicarbazone compounds with the antitumor activity in preparation of an antitumor drug. According to the preparation method, the raw materials are cheap and easy to obtain, the operation is simple, and the prepared indole [2,3-a] pyrrole[3,4-c] carbazole-5,7-diketone-6-thiosemicarbazone compounds have better biological activity and have better application prospect in preparation of an antitumor drug compound.
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Paragraph 0056; 0057; 0061; 0062
(2017/04/03)
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- Bisindolyl maleimide derivative and preparation method and application thereof
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The invention provides a bisindolyl maleimide derivative and a preparation method and application thereof. The bisindolyl maleimide derivative has an excellent alpha-glucosidase inhibition effect and can be used for preventing and treating diabetes.
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Paragraph 0487; 0488; 0684; 0685
(2017/01/02)
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- Bisindolylmaleimide derivative, and preparation method and use thereof
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The invention provides a bisindolylmaleimide derivative, and a preparation method and a use thereof. The bisindolylmaleimide derivative has a good tumor treatment effect, especially has a good treatment effect on some drug-resistant tumors, and can realize accurate treatment of the drug-resistant tumors.
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Paragraph 0490; 0491; 0687; 0688
(2017/04/03)
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- Synthesis and cytotoxic activities of a series of novel N-methylbisindolylmaleimide amino acid ester conjugates
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A series of novel N-methylbisindolylmaleimides and natural amino acid conjugates were synthesized and evaluated for their inhibitory activity against six tumor cell lines. Most of the compounds exhibited moderate in vitro cytotoxic activities in the range
- Wang, Ke,Yan, Zheng,Wang, Nan,Liu, Zhan Zhu
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p. 462 - 465
(2012/06/29)
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- Synthesis and antitumor activity of bisindolylmaleimide and amino acid ester conjugates
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A series of novel bisindolylmaleimide and natural amino acid ester conjugates were synthesized and evaluated for their inhibitory activity against six tumor cell lines. Some compounds displayed interesting cytotoxic profiles. The most active compound 8e s
- Wang, Ke,Li, Xiang-Yan,Chen, Xiao-Guang,Liu, Zhan-Zhu
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scheme or table
p. 36 - 42
(2010/09/04)
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- Synthesis of N-methyl-bisindolylmaleimide amino acid methyl ester conjugates and cytotoxicity study
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A novel series of N-methylbisindolylmaleimides derivatives bearing 2-acetamino acid moieties were synthesized. The cytotoxic activities of these compounds were tested in six tumor cell lines. The most potent compound 8d displayed cytotoxicity against six
- Wang, Ke,Liu, Zhan-Zhu
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scheme or table
p. 4175 - 4179
(2010/10/02)
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- Regioselective animation of 3-Bromoindolylmaleimide with amines
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3-Bromoindolylmaleimide and bisindolylmaleimide were synthesized from succinimide in three steps sequnence consisting of bromination, N-methylation and indole addition in the presence of magnesium and bromoethane. They were subjeced to the regioselective amination with substituted amines to provide 3-aminoindolylmaleimides, 3- amino-N-alkylated indolylmaleimides and N-alkylated bisindolylmaleimides in good yields. The resulting indolylmaleimides represent a new class of potentially bioactive compounds.
- Jiang, Di-Fa,Yang, Yan-Wu,Shao, Zhi-Yu,Zhao, Sheng-Yin
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scheme or table
p. 144 - 148
(2010/08/05)
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- Design and synthesis of N-methylmaleimide indolocarbazole bearing modified 2-acetamino acid moieties as Topoisomerase I inhibitors
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A novel series of N-methylmaleimide indolocarbazole derivatives bearing modified 2-acetamino acid moieties are first reported. The cytotoxic effects of these compounds were tested in five human tumor cell lines. The potent compounds 9a, 9b, 9d, and 9e have been further evaluated for their effect on Topoisomerase I (TOPO I) and cancer cell cycle. It is concluded that the indolocarbazoles with alkyl piperazine or morpholine substituent groups instead of esters or glycosyl residues would have better activities against tumors.
- Li, Zhiyu,Zhai, Fuming,Zhao, Li,Guo, Qinglong,You, Qidong
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scheme or table
p. 406 - 409
(2011/02/26)
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- Bisindolylmaleimides with large stokes shift and long-lasting chemiluminescence properties
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Various bisindolylmaleimides have fluorescence emission maxima wavelengths longer than 500 nm, large Stokes shifts longer than 200 nm, different fluorescence emission wavelengths at an excitation wavelength of 365 nm, and a long-lasting chemiluminescence.
- Nakazono, Manabu,Nanbu, Shinkoh,Uesaki, Akihiro,Kuwano, Ryoichi,Kashiwabara, Manabu,Zaitsu, Kiyoshi
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p. 3583 - 3586
(2008/02/11)
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- Syntheses and biological activities of rebeccamycin analogues with uncommon sugars
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Rebeccamycin analogues containing uncommon sugars and substitutions on the imide nitrogen have been synthesized. Their cytotoxicities were tested in colon cancer and leukemia cells. Their ability to target topoisomerase I was examined using the in vivo co
- Zhang, Guisheng,Shen, Jie,Cheng, Hao,Zhu, Lizhi,Fang, Lanyan,Luo, Sanzhong,Muller, Mark T.,Lee, Gun Eui,Wei, Lijun,Du, Yuguo,Sun, Duxin,Wang, Peng George
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p. 2600 - 2611
(2007/10/03)
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- Synthesis of indolo[2,3-a]pyrrolo[3,4-c]carbazoles by oxidative cyclization of bisindolylmaleimides with a rhodium(III)-copper(II) catalytic system
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A novel catalytic protocol for the synthesis of a series of indolo[2,3-a]pyrrplo[3,4-c]carbazoles based on the bimetallic system RhCl 3·3H2O and Cu(OAc)2·H 2O in the presence of molecular oxygen was investigated
- Witulski, Bernhard,Schweikert, Torsten
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p. 1959 - 1966
(2007/10/03)
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- A mild and selective method for N-Boc deprotection
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A new mild method to remove N-tert-butyloxycarbonyl groups using TBAF in refluxing THF is reported. In all cases, the corresponding N-free products are obtained in good yields. The reactions are selective for acid- and base-sensitive groups, such as tert-butyl and alkyl esters, aldehydes.
- Routier, Sylvain,Saugé, Laurence,Ayerbe, Nathalie,Coudert, Gérard,Mérour, Jean-Yves
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p. 589 - 591
(2007/10/03)
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- Use of bisindolylmaleimide compounds to induce Fas-mediated apoptosis
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The present invention provides a method of inducing apoptosis in target cells of a subject by administering, to the subject a pharmaceutically effective amount of at least one compound of the formula: wherein: R1is hydrogen, C1-C12alkyl, C1-C12substituted alkyl, C3-C7heterocycle, or C3-C7substituted heterocycle, R2and R3are independently H or C1-C12alkyl, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof, wherein following the administration of the compound of Formula I, the target cell is caused to undergo apoptosis.
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- Indolocarbazoles: Potent, selective inhibitors of human cytomegalovirus replication
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In our search for new, safer anti-HCMV agents, we discovered that the natural product Arcyriaflavin A (1a) was a potent inhibitor of HCMV replication in cell culture. A series of analogues (symmetrical indolocarbazoles) was synthesised to investigate structure-activity relationships in this series against a range of herpes viruses (HCMV, VZV, HSV1, and 2). This identified a number of novel, selective and potent inhibitors of HCMV, 12,13-dihydro-2,10-difluoro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-(6H)-dione (1d) being the best example (IC50=40nM, therapeutic index >1450). Compounds described in this series were generally poor inhibitors of protein kinase C βII, and no correlation was found between the ability to inhibit HCMV and the enzyme PKC. Copyright (C) 1999 Elsevier Science Ltd.
- Slater, Martin J.,Cockerill, Stuart,Baxter, Robert,Bonser, Robert W.,Gohil, Kam,Gowrie, Clare,Robinson, J. Edward,Littler, Edward,Parry, Nigel,Randall, Roger,Snowden, Wendy
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p. 1067 - 1074
(2007/10/03)
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- A general approach to the synthesis of bisindolylmaleimides: Synthesis of staurosporine aglycone
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Bisindolylmaleimides are prepared in 65-95% yield by reaction of an indole Grignard with either 2,3-dichloro-N-methylmaleimide or 2,3-dichloromaleimide. A one-step synthesis of arcyriarubin A in 72% yield affords ready access to the staurosporine aglycone
- Faul,Sullivan,Winneroski
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p. 1511 - 1516
(2007/10/02)
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- Inhibitors of Protein Kinase C. 1. 2,3-Bisarylmaleimides
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The design and synthesis of a series of novel inhibitors of protein kinase C (PKC) is described.These 2,3-bisarylmaleimides were derived from the structural lead provided by the indolocarbazoles, staurosporine and K252a.Optimum activity required the imide NH, both carbonyl groups, and the olefinic bond of the maleimide ring. 2,3-Bisindolylmaleimides were the most active, and the potency of these was improved by a chloro substituent at the 5-position of one indole ring (compound 28, IC50 0.11 μM).In a series of (phenylindolyl)maleimides, nitro compound 74 was most active (IC50 0.67 μM).Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA).
- Davis, Peter D.,Hill, Christopher H.,Lawton, Geoffrey,Nixon, John S.,Wilkinson, Sandra E.,et al.
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p. 177 - 184
(2007/10/02)
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