325800-39-3Relevant academic research and scientific papers
Synthesis of new 5-bromo derivatives of indole and spiroindole phytoalexins
O?ená?ová, Lucia,Kutschy, Peter,Gonda, Jozef,Pilátová, Martina,G?nciová, Gabriela,Moj?i?, Ján,Pazdera, Pavel
, p. 635 - 648 (2016)
Electrophilic aromatic substitution is one of the most thoroughly studied reactions in organic chemistry. In the present paper, the 5-brominated spirobrassinol methyl ethers VII, VIII were obtained by electrophilic substitution of the aromatic core of indoline at the C-5 position in the presence of various brominating agents. The same products were also prepared from 5-bromoindole (IX) following the sequence for the synthesis 1-methoxyspirobrassinol methyl ether (V) from indoline. In addition, the new related 5-bromospiroindoline derivatives XX-XXIII were synthesised and their biological activity on human tumour cell lines was examined. The presence of bromine in the indole or indoline skeleton at the C-5 position resulted in the partial increase in anticancer activity on leukaemia cell lines (Jurkat, CEM). The structures of the newly prepared products were determined by 1H and 13C NMR spectroscopy, including HSQC, HMBC, COSY, NOESY and DEPT measurements.
Structure-guided design, synthesis, and biological evaluation of (2-(1 H-Indol-3-yl)-1 H-imidazol-4-yl)(3,4,5-trimethoxyphenyl) methanone (ABI-231) analogues targeting the colchicine binding site in Tubulin
Wang, Qinghui,Arnst, Kinsie E.,Wang, Yuxi,Kumar, Gyanendra,Ma, Dejian,White, Stephen W.,Miller, Duane D.,Li, Wei,Li, Weimin
, p. 6734 - 6750 (2019/08/20)
ABI-231 is a potent, orally bioavailable tubulin inhibitor that interacts with the colchicine binding site and is currently undergoing clinical trials for prostate cancer. Guided by the crystal structure of ABI-231 in complex with tubulin, we performed structure-activity relationship studies around the 3-indole moiety that led to the discovery of several potent ABI-231 analogues, most notably 10ab and 10bb. The crystal structures of 10ab and 10bb in complex with tubulin confirmed their improved molecular interactions to the colchicine site. In vitro, biological studies showed that new ABI-231 analogues disrupt tubulin polymerization, promote microtubule fragmentation, and inhibit cancer cell migration. In vivo, analogue 10bb not only significantly inhibits primary tumor growth and decreases tumor metastasis in melanoma xenograft models but also shows a significant ability to overcome paclitaxel resistance in a taxane-resistant PC-3/TxR model. In addition, pharmacological screening suggested that 10bb has a low risk of potential off-target function.
Indole-substituted hydrazide derivatives and uses thereof
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Paragraph 0166; 0199-0202, (2018/11/03)
The invention discloses indole-substituted hydrazide derivatives and a use thereof, concretely relates to novel indole-substituted hydrazide derivatives and a medicinal composition including the abovecompounds, a use of the derivatives and the medicinal composition in the protection of nerve cells, and also relates to a method for preparing the compounds and the medicinal composition, and a use of the compounds and the medicinal composition in the preparation of drugs for treating diseases associated with glutamate excitotoxicity and oxidative stress damage or free radicals, or neurodegenerative diseases, especially the Alzheimer disease.
Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents
Pedada, Srinivasa Rao,Yarla, Nagendra Sastry,Tambade, Pawan J.,Dhananjaya, Bhadrapura Lakkappa,Bishayee, Anupam,Arunasree, Kalle M.,Philip, Gundala Harold,Dharmapuri, Gangappa,Aliev, Gjumrach,Putta, Swathi,Rangaiah, Gururaja
, p. 289 - 297 (2018/04/19)
Secretory phospholipase A2 (sPLA2) is an important enzyme that plays a key role in various inflammatory diseases including cancer and its inhibitors have been developed as preventive or therapeutic agents. In the present study, a series of new indole containing isoxazole derivatives (10a–10o) is synthesized and evaluated for their sPLA2 inhibitory activities. All compounds (10a–10o) showed significant sPLA2 inhibition activities both in vitro and in vivo studies which is substantiated in in silico studies. Among all the tested compounds, 10o showed potent sPLA2 inhibition activity, that is comparable or more to ursolic acid (positive control). Further studies demonstrated that 10o showed in vitro antiproliferative activity when tested against MCF-7 breast and DU145 prostate cancer cells. Furthermore, compounds 10a–10o obeyed lipinsky's rule of 5 and suggesting druggable properties. The in vitro, in vivo and in silico results are encouraging and warrant pre-clinical studies to develop sPLA2-inhibitory compound 10o as novel therapeutic agent for various inflammatory disorders and several malignancies.
Metal-free trifluoromethylation of aromatic and heteroaromatic aldehydes and ketones
Qiao, Yupu,Si, Tuda,Yang, Ming-Hsiu,Altman, Ryan A.
, p. 7122 - 7131 (2014/08/18)
The ability to convert simple and common substrates into fluoroalkyl derivatives under mild conditions remains an important goal for medicinal and agricultural chemists. One representative example of a desirable transformation involves the conversion of aromatic and heteroaromatic ketones and aldehydes into aryl and heteroaryl β,β,β-trifluoroethylarenes and -heteroarenes. The traditional approach for this net transformation involves stoichiometric metals and/or multistep reaction sequences that consume excessive time, material, and labor resources while providing low yields of products. To complement these traditional strategies, we report a one-pot metal-free decarboxylative procedure for accessing β,β,β- trifluoroethylarenes and -heteroarenes from readily available ketones and aldehydes. This method features several benefits, including ease of operation, readily available reagents, mild reaction conditions, high functional-group compatibility, and scalability.
Practical, asymmetric synthesis of aromatic-substituted bulky and hydrophobic tryptophan and phenylalanine derivatives
Wang, Wei,Xiong, Chiyi,Zhang, Junyi,Hruby, Victor J
, p. 3101 - 3110 (2007/10/03)
Aromatic ring substituted tryptophans and phenylalanines can provide valuable tools in developing highly potent and selective peptide ligands with specific structural features in addition to providing a large lipophilic surface for binding to receptors and for crossing membrane barriers. An efficient method for the synthesis of these novel amino acids has been developed. In the approach, asymmetric hydrogenations of α-enamides using Burk's DuPHOS-based Rh (I) catalysts generated high enantiomerically pure α-amino acid derivatives, which subsequently underwent Suzuki cross couplings with boronic acid derivatives to afford these aromatic substituted amino acids in high yields and high enantioselectivity. The method can allow for the preparation of such amino acids in large scales for extensive structure-activity studies.
Practical, asymmetric synthesis of aromatic-substituted bulky and hydrophobic tryptophan derivatives
Wang, Wei,Xiong, Chiyi,Yang, Jianqing,Hruby, Victor J
, p. 7717 - 7719 (2007/10/03)
An efficient method for the synthesis of novel aromatic substituted, bulky and hydrophobic tryptophan derivatives has been developed. Asymmetric hydrogenations of α-enamide 5 using Burk's DuPHOS-based catalysts generated high enantiomerically pure D- and L-α-amino acid derivatives 6, which subsequently underwent Suzuki cross couplings with boronic acid derivatives to afford aromatic substituted tryptophan derivatives 7 and 8 in high yields. The method can allow for the preparation of such amino acids in large-scales for extensive structure-activity studies.
