- Design, synthesis and evaluation of novel (S)-tryptamine derivatives containing an allyl group and an aryl sulfonamide unit as anticancer agents
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A series of (S)-tryptamine derivatives containing an allyl group and an aryl sulfonamide unit were designed, synthesized and evaluated for their potential application as anticancer agents. The structures of the synthesized compounds were characterized by 1H NMR, 13C NMR and ESI-MS spectral analyses. The target compounds were evaluated for their in vitro cytotoxicity against HepG2, HeLa, CNE1 and A549 human cancer cell lines. Some of the synthesized compounds showed moderate to good anticancer activities against four selected cancer cell lines, among of which 6ag was found to be the most active analogue possessing IC50 values 16.5–18.7 μM. Further mechanism studies revealed that compound 6ag could significantly induce HepG2 cell cycle arrest at G1 phase, promote cell apoptosis, and inhibit the colony formation as well.
- Guo, Zhenbo,Xu, Yiming,Peng, Yujie,Haroon ur Rashid,Quan, Wei,Xie, Peng,Wu, Lichuan,Jiang, Jun,Wang, Lisheng,Liu, Xu
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Read Online
- Copper-catalyzed carbonylative transformations of indoles with hexaketocyclohexane
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With hexaketocyclohexane octahydrate as the carbon monoxide source, a novel procedure for copper-catalyzed direct double carbonylation of indoles has been established. Using alcohols as reaction partners, moderate to good yields of the desired double carbonylation products have been obtained. Wide functional group tolerance and substrate scope can be observed.
- Wang, Zechao,Yin, Zhiping,Wu, Xiao-Feng
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Read Online
- Concise synthesis of the (±)-Nb-desmethyl-meso- chimonanthine
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The first total synthesis of the bis-pyrroloindoline alkaloid (±)-Nb-desmethyl-meso-chimonanthine, having a pseudo C 2-symmetry, was realised in a seven-step convergent sequence without the use of protecting groups. The Royal Society of Chemistry 2006.
- Menozzi, Candice,Dalko, Peter I.,Cossy, Janine
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Read Online
- S -indole benzamide derivative as well as preparation method and application thereof
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S - Indole benzamide derivatives as well as a preparation method and application thereof relate to the technical field of pharmacy. The derivative has a structural formula. The specific preparation method comprises the following steps: taking indole as a starting raw material and performing acylation reaction. Reaction, oxidation reaction, (R)- (+) -tert-butylsulfenamide asymmetric synthesis reaction, hydrolysis reaction and acylation reaction to give the target product. By means of the method, a novel antiviral drug with a development prospect can be obtained, and the yield is high.
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Paragraph 0030-0033
(2021/09/15)
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- 3-(7-Azaindolyl)-4-indolylmaleimides as a novel class of mutant isocitrate dehydrogenase-1 inhibitors: Design, synthesis, and biological evaluation
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A series of 3-(7-azainodyl)-4-indolylmaleimides was designed, synthesized, and evaluated for their isocitrate dehydrogenase 1 (IDH1)/R132H inhibitory activities. Many compounds such as 11a, 11c, 11e, 11g, and 11s exhibited favorable inhibitory effects on IDH1/R132H and were highly selective against the wild-type IDH1. Evaluation of the biological activities at the cellular level showed that compounds 11a, 11c, 11e, 11g, and 11s could effectively suppress the production of 2-hydroxyglutaric acid in U87MG cells expressing IDH1/R132H. Preliminary structure–activity relationship (SAR) and molecular modeling studies were discussed based on the experimental data obtained. These findings may provide new insights into the development of novel IDH1/R132H inhibitors.
- Hu, Yuanyuan,Gao, Anhui,Liao, Honghui,Zhang, Mengmeng,Xu, Gaoya,Gao, Lixin,Xu, Lei,Zhou, Yubo,Gao, Jianrong,Ye, Qing,Li, Jia
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- Design and synthesis of (aza)indolyl maleimide-based covalent inhibitors of glycogen synthase kinase 3β
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As an important kinase in multiple signal transduction pathways, GSK-3β has been an attractive target for chemical probe discovery and drug development. Compared to numerous reversible inhibitors that have been developed, covalent inhibitors of GSK-3β are
- Yang, Zhimin,Liu, Hui,Pan, Botao,He, Fengli,Pan, Zhengying
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supporting information
p. 4127 - 4140
(2018/06/12)
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- A convenient synthesis of indole and 1,4-dihydropyridine hybrid macromolecules by dimerization of [2-(1h-indol-3-yl)ethyl]pyridinium salts
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The design and synthesis of a novel type of macrocyclic compounds containing indole and 1,4-dihydropyridine heterocyclic subunits is presented. The key reaction involved in the synthesis was a base-mediated dimerization of [2-(1H-indol-3-yl)ethyl]pyridinium salts. The structure of the macrocycles was unambiguously confirmed by NMR and HRMS spectroscopic and X-ray single crystal diffraction.
- Ling, Gang,Zhang, Jing,Zhang, Rong-Zheng,Han, Fu-She
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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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supporting information
p. 513 - 516
(2017/09/13)
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- An indole-based conjugated microporous polymer: A new and stable lithium storage anode with high capacity and long life induced by cation-π interactions and a N-rich aromatic structure
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An indole-based conjugated microporous polymer, poly(bisindolylmaleimide) (PBIM), with superior electrochemical performance as an anode material for LIBs has been obtained by FeCl3-promoted oxidative coupling polymerization. Benefiting from reversible cation-π interactions and a unique aromatic structure containing N heteroatoms, the prepared PBIM anode shows high capacity (1172 mA h g-1, 50 mA g-1), outstanding cycle life (1000 cycles), and remarkable rate performance (214 mA h g-1, 2.5C).
- Wei, Wenxuan,Chang, Guanjun,Xu, Yewei,Yang, Li
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supporting information
p. 18794 - 18798
(2018/10/20)
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- [18F]MALEIMIDE-BASED GLYCOGEN SYNTHASE KINASE-3BETA LIGANDS FOR POSITRON EMISSION TOMOGRAPHY IMAGING AND RADIOSYNTHESIS METHOD
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The present invention provides a compound having the structure: (Formula I), and a method of inhibiting Glycogen synthase kinase-3 β (GSK-3β) in a subject comprising administering to the subject said compound, so as to thereby inhibit the GSK-3β in the subject.
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Page/Page column 41
(2018/08/03)
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- Development of [18F]Maleimide-Based Glycogen Synthase Kinase-3β Ligands for Positron Emission Tomography Imaging
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Dysregulation of glycogen synthase kinase-3β (GSK-3β) is implicated in the pathogenesis of neurodegenerative and psychiatric disorders. Thus, development of GSK-3β radiotracers for positron emission tomography (PET) imaging is of paramount importance, because such a noninvasive imaging technique would allow better understanding of the link between the activity of GSK-3β and central nervous system disorders in living organisms, and it would enable early detection of the enzyme’s aberrant activity. Herein, we report the synthesis and biological evaluation of a series of fluorine-substituted maleimide derivatives that are high-affinity GSK-3β inhibitors. Radiosynthesis of a potential GSK-3β tracer [18F]10a is achieved. Preliminary in vivo PET imaging studies in rodents show moderate brain uptake, although no saturable binding was observed in the brain. Further refinement of the lead scaffold to develop potent [18F]-labeled GSK-3 radiotracers for PET imaging of the central nervous system is warranted.
- Hu, Kongzhen,Patnaik, Debasis,Collier, Thomas Lee,Lee, Katarzyna N.,Gao, Han,Swoyer, Matthew R.,Rotstein, Benjamin H.,Krishnan, Hema S.,Liang, Steven H.,Wang, Jin,Yan, Zhiqiang,Hooker, Jacob M.,Vasdev, Neil,Haggarty, Stephen J.,Ngai, Ming-Yu
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p. 287 - 292
(2017/03/17)
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- An environmentally friendly protocol for oxidative halocyclization of tryptamine and tryptophol derivatives
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An environmentally friendly and efficient protocol (KX/oxone) for oxidative halocyclization of tryptamine/tryptophol derivatives was developed and demonstrated with 28 examples and concise total synthesis of cyclotryptamine alkaloid protubonines A and B. The distinct advantage of this protocol over all previous methods is that no organic byproduct is generated from a halogenating agent or oxidant, thus greatly reducing the environmental impact of halocyclization and facilitating the post-reaction purification.
- Xu, Jun,Tong, Rongbiao
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p. 2952 - 2956
(2017/07/24)
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- 3 - (1, 2, 4 - triazole [4, 3 - a] pyridine - 3 - yl) - 4 - (1H - Indol - 3 - yl) maleimide derivatives and its preparation method and application
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The invention provides a 3-(1,2,4-triazolo(4,3-a)pyridine-3-yl)-4-(1H-indole-3-yl)maleimide derivative with a novel structure and a preparation method and application of the derivative. The compound can be used for treating ischemic cerebral apoplexy. The general structural formula of the compound is shown in the specification.
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Paragraph 0035; 0036
(2017/08/25)
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- Synthesis and biological evaluation of 3-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides as potent, selective GSK-3β inhibitors and neuroprotective agents
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A series of novel 3-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides were designed, prepared and evaluated for their GSK-3β inhibitory activities. Most compounds showed high potency to GSK-3β inhibition with high selectivity. Among them, compounds 7c, 7f, 7h, 7l and 7m significantly reduced GSK-3β substrate Tau phosphorylation at Ser396 in primary neurons, showing the inhibition of cellular GSK-3β. In the in vitro neuronal injury models, compounds 7c, 7f, 7h, 7l and 7m prevented neuronal death against glutamate, oxygen-glucose deprivation and nutrient serum deprivation which are associated with cerebral ischemic stroke. In the in vivo cerebral ischemia animal model, compound 7f reduced infarct size by 15% and improved the neurological deficit following focal cerebral ischemia. These findings may provide new insights into the development of novel GSK-3β inhibitors with potential neuroprotective activity.
- Ye, Qing,Mao, Weili,Zhou, Yubo,Xu, Lei,Li, Qiu,Gao, Yuanxue,Wang, Jing,Li, Chenhui,Xu, Yazhou,Xu, Yuan,Liao, Hong,Zhang, Luyong,Gao, Jianrong,Li, Jia,Pang, Tao
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p. 1179 - 1188
(2015/03/04)
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- Synthesis and Evaluation of 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides as Novel GSK-3β Inhibitors and Anti-Ischemic Agents
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A series of novel 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides were designed, synthesized, and biologically evaluated for their GSK-3β inhibitory activities. Most compounds showed favorable inhibitory activities against GSK-3β protein. Among them, compounds 5n, 5o, and 5p significantly reduced GSK-3β substrate tau phosphorylation at Ser396 in primary neurons, indicating inhibition of cellular GSK-3β activity. In the in vitro neuronal injury models, compounds 5n, 5o, and 5p prevented neuronal death against glutamate, oxygen-glucose deprivation, and nutrient serum deprivation which are closely associated with cerebral ischemic stroke. In the in vivo cerebral ischemia animal model, compound 5o reduced infarct size by 10% and improved the neurological deficit. The results may provide new insights into the development of novel GSK-3β inhibitors with potential neuroprotective activity against brain ischemic stroke.
- Ye, Qing,Li, Qiu,Zhou, Yubo,Xu, Lei,Mao, Weili,Gao, Yuanxue,Li, Chenhui,Xu, Yuan,Xu, Yazhou,Liao, Hong,Zhang, Luyong,Gao, Jianrong,Li, Jia,Pang, Tao
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p. 746 - 752
(2015/03/30)
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- Dearomatization of tryptophols via a vanadium-catalyzed asymmetric epoxidation and ring-opening cascade
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An enantioselective epoxidation of tryptophols followed by an intramolecular epoxide opening reaction was realized by chiral vanadium catalysts derived from C2 symmetric bis-hydroxamic acid (BHA) ligands. 3a-Hydroxyfuroindoline derivatives with up to 89% yield and 90% ee were obtained under mild reaction conditions.
- Han, Long,Liu, Chuan,Zhang, Wei,Shi, Xiao-Xin,You, Shu-Li
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p. 1231 - 1233
(2014/02/14)
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- Pd(0)-catalyzed alkenylation and allylic dearomatization reactions between nucleophile-bearing indoles and propargyl carbonate
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Spiroindolenine derivatives were synthesized by intermolecular Pd-catalyzed dearomatization of indoles. The reaction between nucleophile bearing indoles and propargyl carbonate proceeds in a cascade fashion providing spiroindolenines or spiroindolines in
- Gao, Run-Duo,Liu, Chuan,Dai, Li-Xin,Zhang, Wei,You, Shu-Li
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supporting information
p. 3919 - 3921
(2014/08/18)
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- Dissecting metabolic puzzles through isotope feeding: A novel amino acid in the biosynthetic pathway of the cruciferous phytoalexins rapalexin A and isocyalexin A
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Understanding defence pathways of plants is crucial to develop disease-resistant agronomic crops, an important element of sustainable agriculture. For this reason, natural plant defenses such as phytoalexins, involved in protecting plants against microbial pathogens, have enormous biotechnological appeal. Crucifers are economically important plants, with worldwide impact as oilseeds, vegetables of great dietetic value and even nutraceuticals. Notably, the intermediates involved in the biosynthetic pathways of unique cruciferous phytoalexins such as rapalexin A and isocyalexin A remain unknown. Toward this end, using numerous perdeuterated compounds, we have established the potential precursors of these unique phytoalexins and propose for the first time their detailed biosynthetic pathway. This pathway involves a variety of intermediates and a novel amino acid as the central piece of this complex puzzle. This work has set the stage for the discovery of enzymes and genes of the biosynthetic pathway of cruciferous phytoalexins of unique scaffolds.
- Pedras, M. Soledade C.,Yaya, Estifanos E.
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p. 1149 - 1166
(2013/03/29)
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- Synthesis and biological evaluation of 3-benzisoxazolyl-4-indolylmaleimides as potent, selective inhibitors of glycogen synthase kinase-3β
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A series of novel 3-benzisoxazolyl-4-indolyl-maleimides were synthesized and evaluated for their GSK-3β inhibitory activity. Most compounds exhibited high inhibitory potency towards GSK-3β. Among them, compound 7j with an IC50 value of 0.73 nM was the most promising GSK-3β inhibitor. Preliminary structure-activity relationships were examined and showed that different substituents on the indole ring and N1-position of the indole ring had varying degrees of influence on the GSK-3β inhibitory potency. Compounds 7c, 7f, 7j-l and 7o-q could obviously reduce Aβ-induced Tau hyperphosphorylation by inhibiting GSK-3β in a cell-based functional assay.
- Ye, Qing,Li, Meng,Zhou, Yubo,Pang, Tao,Xu, Lei,Cao, Jiayi,Han, Liang,Li, Yujin,Wang, Weisi,Gao, Jianrong,Li, Jia
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p. 5498 - 5516
(2013/06/27)
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- Metal-free, mild, nonepimerizing, chemo- and enantio- or diastereoselective N-alkylation of amines by alcohols via oxidation/imine-iminium formation/reductive amination: A pragmatic synthesis of octahydropyrazinopyridoindoles and higher ring analogues
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A mild step and atom-economical nonepimerizing chemo- and enantioselective N-alkylating procedure has been developed via oxidation/imine-iminium formation/reduction cascade using TEMPO-BAIB-HEH-Bronsted acid catalysis in DMPU as solvent and a stoichiometric amount of amine. The optimized conditions were further extended for the nonenzymatic kinetic resolution of the chiral amine thus formed under nonenzymatic in situ hydrogen-transfer conditions using VAPOL-derived phosphoric acid (VAPOL-PA) as the Bronsted acid catalyst. The enantioselective cascade of the presented reaction was successfully utilized in the synthesis of octahydropyrazinopyridoindole and its higher ring analogues.
- Khan, Imran A.,Saxena, Anil K.
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p. 11656 - 11669
(2014/01/06)
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- Design, synthesis, and evaluation of 3-aryl-4-pyrrolyl-maleimides as glycogen synthase kinase-3β inhibitors
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A series of 3-aryl-4-pyrrolyl-maleimides were designed, synthesized, and evaluated for their glycogen synthase kinase-3β (GSK-3β) inhibitory activity. Most compounds exhibited potent activity against GSK-3β. Among them, compounds 11a, 11c, 11h, 11i, and 11j significantly reduced Aβ-induced Tau hyperphosphorylation, showing the inhibition of GSK-3β at the cellular level. Structure-activity relationships were discussed based on the experimental data obtained. Most compounds in a new series of 3-aryl-4-pyrrolyl-maleimides exhibited potent glycogen synthase kinase-3β (GSK-3β) inhibitory activity. Compounds 11a, 11c, 11h, 11i, and 11j reduced Aβ-induced Tau hyperphosphorylation, showing inhibition of GSK-3β at the cellular level. Copyright
- Ye, Qing,Li, Meng,Zhou, Yu-Bo,Cao, Jia-Yu,Xu, Lei,Li, Yu-Jin,Han, Liang,Gao, Jian-Rong,Hu, Yong-Zhou,Li, Jia
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p. 349 - 358
(2013/07/19)
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- Rhodium-catalyzed enantioselective 1,2-addition of arylboronic acids to heteroaryl α-ketoesters for synthesis of heteroaromatic α-hydroxy esters
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The first example of catalytic asymmetric 1,2-addition of arylboronic acids to heteroaryl α-ketoesters has been developed for the highly efficient and enantioselective synthesis of quaternary carbon-containing heteroaromatic α-hydroxy esters. The reaction works well with a variety of α-ketoesters including 3-indoleglyoxylates, 3-benzofuranglyoxylates and 3-benzothiopheneglyoxylates under very mild conditions, affording the corresponding products in moderate to good yields with high enantiomeric excesses (up to 97%).
- Wang, Hui,Zhu, Ting-Shun,Xu, Ming-Hua
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p. 9158 - 9164,7
(2012/12/12)
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- Rhodium-catalyzed enantioselective 1,2-addition of arylboronic acids to heteroaryl α-ketoesters for synthesis of heteroaromatic α-hydroxy esters
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The first example of catalytic asymmetric 1,2-addition of arylboronic acids to heteroaryl α-ketoesters has been developed for the highly efficient and enantioselective synthesis of quaternary carbon-containing heteroaromatic α-hydroxy esters. The reaction works well with a variety of α-ketoesters including 3-indoleglyoxylates, 3-benzofuranglyoxylates and 3-benzothiopheneglyoxylates under very mild conditions, affording the corresponding products in moderate to good yields with high enantiomeric excesses (up to 97%).
- Wang, Hui,Zhu, Ting-Shun,Xu, Ming-Hua
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p. 9158 - 9164
(2013/01/15)
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- [11C]Enzastaurin, the first design and radiosynthesis of a new potential PET agent for imaging of protein kinase C
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Enzastaurin (LY317615) is a potent and selective protein kinase C (PKC) inhibitor with an IC50 value of ~6 nM. [11C] Enzastaurin (3-(1-[11C]methyl-1H-indol-3-yl)-4-[1-[1-(2- pyridinylmethyl)-4-piperidinyl]-1H-indol-3-yl]-1H-pyrrole-2,5-dione), a new potential PET agent for imaging of PKC, was first designed and synthesized in 20-25% decay corrected radiochemical yield and 370-555 GBq/μmol specific activity at end of bombardment (EOB). The synthetic strategy was to prepare a carbon-11-labeled maleic anhydride intermediate followed by the conversion to maleimide.
- Wang, Min,Xu, Lu,Gao, Mingzhang,Miller, Kathy D.,Sledge, George W.,Zheng, Qi-Huang
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p. 1649 - 1653
(2011/05/11)
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- The first synthesis of [11C]SB-216763, a new potential PET agent for imaging of glycogen synthase kinase-3 (GSK-3)
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SB-216763 is a novel, potent and selective glycogen synthase kinase-3 (GSK-3) inhibitor with an IC50 value of 34 nM. [11C]SB- 216763 (3-(2,4-dichlorophenyl)-4-(1-[11C]methyl-1H-indol-3-yl)-1H- pyrrole-2,5-dione), a new potential PET agent for imaging of GSK-3, was first designed and synthesized in 20-30% decay corrected radiochemical yield and 370-555 GBq/μmol specific activity at end of bombardment (EOB). The synthetic strategy was to prepare a carbon-11-labeled maleic anhydride intermediate followed by the conversion to maleimide.
- Wang, Min,Gao, Mingzhang,Miller, Kathy D.,Sledge, George W.,Hutchins, Gary D.,Zheng, Qi-Huang
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experimental part
p. 245 - 249
(2011/02/27)
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- Labeled 3-aryl-4-indolylmaleimide derivatives and their potential as angiogenic PET biomarkers
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In a continued effort to find a suitable PET tracer for visualization of angiogenic processes, we explored the 3,4-diarylmaleimide family, known to have high affinity and selectivity towards the VEGFR-TKs. One previously reported agent and three new halogen-containing 3,4-diarylmaleimide derivatives were synthesized. The four maleimide derivatives were evaluated for their affinity and selectivity towards the VEGFRs and exhibited promising results. An automated carbon-11 radiolabeling route with a total synthesis time of 50 min successfully labeled the lead compound, resulting in 1.55 ± 0.15 GBq of tracer with a radiochemical yield of 20 ± 2%, 96% radiochemical purity and a SA of 111 ± 22 GBq/μmol (EOB, n = 5). The tracer possessed high stability in in vitro blood stability tests and specific VEGFR-TK binding profiles in intact cell binding experiments. Tracer lipophilicity was evaluated in an n-octanol/phosphate buffer system giving a Log D7.4 of 1.99 ± 0.04. For the in vivo experiments, two animal models were used. The first was a U87 glioma tumor model, frequently reported in the literature and the second, a newly developed 293/KDR tumor model. Both models were validated for VEGFR-2 expression and used in in vivo biodistribution studies. These studies revealed low accumulation and rapid washout of the tracer from tumor tissue. High accumulation of activity in the liver prompted us to examine the tracer's in vitro stability to liver microsomes, revealing low resistance to P450 metabolism. In spite of encouraging in vitro results, the labeled lead tracer failed to accumulate in VEGFR-2 overexpressing tumors. It is possible that poor resistance to P450 metabolism reduces tracer's circulation leading to low tumor accumulation.
- Ilovich, Ohad,Billauer, Hana,Dotan, Sharon,Mishani, Eyal
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experimental part
p. 612 - 620
(2010/05/02)
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- Cleavage of alkoxycarbonyl protecting groups from carbamates by t-BuNH2
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An efficient, simple protocol for the selective cleavage of a variety of N-alkoxycarbonyl protecting groups by t-BuNH2/MeOH is described. The scope of the procedure was explored for a series of indole, aniline and pyrrolidine carbamate derivatives containing other potentially reactive functional groups affording a clean cleavage of the carbamate group.
- Suárez-Castillo, Oscar R.,Montiel-Ortega, Luis Alberto,Meléndez-Rodríguez, Myriam,Sánchez-Zavala, Maricruz
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- DRUG FOR NERVE REGENERATION
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An object of the present invention is to provide a nerve regenerating drug, an agent for the promotion of neuropoiesis of a neural stem cell, a neuron obtained by culturing a neural stem cell in the presence of the agent for the promotion of neuropoiesis,
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Page/Page column 26
(2011/04/19)
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- Novel indolylindazolylmaleimides as inhibitors of protein kinase C-β: Synthesis, biological activity, and cardiovascular safety
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Novel indolylindazolylmaleimides were synthesized and examined for kinase inhibition. We identified low-nanomolar inhibitors of PKC-β with good to excellent selectivity vs other PKC isozymes and GSK-3β. In a cell-based functional assay, 8f and 8i effectiv
- Zhang, Han-Cheng,Derian, Claudia K.,McComsey, David F.,White, Kimberly B.,Ye, Hong,Hecker, Leonard R.,Li, Jian,Addo, Michael F.,Croll, Diane,Eckardt, Annette J.,Smith, Charles E.,Li, Quan,Cheung, Wai-Man,Conway, Bruce R.,Emanuel, Stuart,Demarest, Keith T.,Andrade-Gordon, Patricia,Damiano, Bruce P.,Maryanoff, Bruce E.
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p. 1725 - 1728
(2007/10/03)
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- Neuroprotective and anti-proliferative compounds
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This invention features ring-substituted pyrrolo-β-carboline derivatives and ring-substitution and structural derivatives of 3-(1H-indol-3-yl)-1H-pyrrole-2,5-dione of formulas (I-III), which are useful as neuroprotective and anti-proliferative compounds. Also disclosed are methods for the preparation of these compounds, selected biological profiles and uses of these compounds in the treatment of various neurodegenerative and inflammatory diseases of the human nervous system and in the treatment of various other proliferative disorders characterized by loss of growth or cellular differentiation control including, but not limited to, cancer and inflammation.
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- Novel, potent and selective cyclin D1/CDK4 inhibitors: Indolo[6,7-a]pyrrolo[3,4-c]carbazoles
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The synthesis and CDK inhibitory properties of a series of indolo[6,7-a]pyrrolo[3,4-c]carbazoles is reported. In addition to their potent CDK activity, the compounds display antiproliferative activity against two human cancer cell lines. These inhibitors also effect strong G1 arrest in these cell lines and inhibit Rb phosphorylation at Ser780 consistent with inhibition of cyclin D1/CDK4.
- Engler, Thomas A.,Furness, Kelly,Malhotra, Sushant,Sanchez-Martinez, Concha,Shih, Chuan,Xie, Walter,Zhu, Guoxin,Zhou, Xun,Conner, Scott,Faul, Margaret M.,Sullivan, Kevin A.,Kolis, Stanley P.,Brooks, Harold B.,Patel, Bharvin,Schultz, Richard M.,DeHahn, Tammy B.,Kirmani, Kashif,Spencer, Charles D.,Watkins, Scott A.,Considine, Eileen L.,Dempsey, Jack A.,Ogg, Catherine A.,Stamm, Nancy B.,Anderson, Bryan D.,Campbell, Robert M.,Vasudevan, Vasu,Lytle, Michelle L.
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p. 2261 - 2267
(2007/10/03)
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- SUBSTITUTED PYRROLINES AS KINASE INHIBITORS
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The present invention is directed to novel substituted pyrroline compounds useful as kinase or dual-kinase inhibitors, methods for producing such compounds and methods for treating or ameliorating a kinase or dual-kinase mediated disorder.
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- Improved Synthesis of Isogranulatimide, a G2 Checkpoint Inhibitor. Syntheses of Didemnimide C, Isodidemnimide A, Neodidemnimide A, 17-Methylgranulatimide, and Isogranulatimides A-C
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A concise, improved synthesis of isogranulatimide (6), a naturally occurring substance with G2 checkpoint inhibition activity, is described. Also reported are the syntheses of didemnimide C (18), isodidemnimide A (24), neodidemnimide A (36), 17-methylgranulatimide (9), and isogranulatimides A (10), B (11), and C (12). Compounds 9-12, congeners of isogranulatimide (6), are now available for biological evaluation.
- Piers, Edward,Britton, Robert,Andersen, Raymond J.
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p. 530 - 535
(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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- Synthesis and antimicrobial activities of monoindolyl- and bisindolyloximes
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Six monoindolyl- and bisindolyloximes structurally related to protein kinase C inhibitors bisindolylmaleimides were synthezised. They did not have protein kinase C inhibitory properties but exhibited interesting antimicrobial activities. Their antibacterial activities against several strains of pathogenic and non-pathogenic Gram-positive and Gram-negative bacteria are described. The bisindolyl monooxime isomers exhibited a marked activity against the three strains of Staphylococcus aureus tested and against Escherichia coli 1507E.
- Prudhomme, Michelle,Sancelme, Martine,Bonnefoy, Alain,Fabbro, Doriano,Meyer, Thomas
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p. 161 - 165
(2007/10/03)
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- Synthesis of rebeccamycin and 11-dechlororebeccamycin
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Glycosylated 7-chloroindole-3-acetamide 9, prepared in four steps and 26% yield from 7-chloroindole (1), was condensed with methyl 7-chloroindole- 3-glyoxylate 11 and methyl indole-3-glyoxylate 12 to provide bisindolylmaleimides 7 and 8 in 86% and 84% yield, respectively. Oxidation of 7 and 8 followed by debenzylation provided a new approach to the synthesis of rebeccamycin and completed for the first time a synthesis of 11- dechlororebeccamycin.
- Faul,Winneroski,Krumrich
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p. 2465 - 2470
(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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- Total synthesis of didemnimide A and B
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The total synthesis of didemnimide A and didemnimide B, novel predator- deterrent alkaloids from the Caribbean mangrove ascidian Didemnum conchyliatum, is described.
- Hughes, Terry V.,Cava, Michael P.
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p. 9629 - 9630
(2007/10/03)
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- Alboinon, an oxadiazinone alkaloid from the ascidian Dendrodoa grossularia
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The ascidian Dendrodoa grossularia, collected in the Baltic Sea, contains the new 1,3,5-oxadiazin-2-one alkaloid alboinon (1).
- Bergmann, Tanja,Schories, Dirk,Steffan, Bert
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p. 2055 - 2060
(2007/10/03)
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- Hexahydropyrroloindoles - Attempts to Synthesize 2-Indolyl Thioethers
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The N-tryptamine derivatives 9, 11, 12, and 19 with the functional groups CN, CONH2, CO2H, and CO2Me, respectively, in the α position to the indole ring have been synthesized.Sensitized photooxiation of 9, 12, 19, N-Boc--tryptophan (21), and N-Boc-tryptamine (22) affords the hexahydropyrroloindoles 23-27, in the case of 11 the ring closure occurs at the amine nitrogen to give the ketone 28, N-Boc-homotryptamine (31) yields the hexahydropyridoindole 32, whereas no azetidine formation from 2-(3-indolyl)glycine (36) is observed.The oxi mes 34a and 34 b, intermediates in the synthesis of 36, have been separated chromatographically and characterized NMR spectroscopically as E and Z-isomers, respectively.- Attempts to introduce with cysteine derivatives a thioether group in position 2 of the compounds described above, failed. 21, 22, 26, 27, and N-Boc-2-(3-indolyl)propylamine (43), bearing a methyl group in the α position to the indole ring, and its photooxidation product 44 show only thin-layer chromatographically detectable thioether formation.
- Droste, Holger,Wieland, Theodor
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p. 901 - 910
(2007/10/02)
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