883-55-6Relevant academic research and scientific papers
Exploration of the antibiotic potentiating activity of indolglyoxylpolyamines
Cadelis, Melissa M.,Pike, Elliot I.W.,Kang, Weirong,Wu, Zimei,Bourguet-Kondracki, Marie-Lise,Blanchet, Marine,Vidal, Nicolas,Brunel, Jean Michel,Copp, Brent R.
, (2019/09/30)
A series of substituted di-indolglyoxylamido-spermine analogues were prepared and evaluated for intrinsic antimicrobial properties and the ability to enhance antibiotic action. As a compound class, intrinsic activity was typically observed towards Gram-positive bacteria and the fungus Cryptococcus neoformans, with notable exceptions being the 5-bromo- and 6-chloro-indole analogues which also exhibited modest activity (MIC 34–50 μM) towards the Gram-negative bacteria Escherichia coli and Klebsiella pneumoniae. Several analogues enhanced the activity of doxycycline towards the Gram-negative bacteria Pseudomonas aeruginosa, E. coli, K. pneumoniae and Acinetobacter baumannii. Of particular note was the identification of five antibiotic enhancing analogues (5-Br, 7-F, 5-Me, 7-Me, 7-OMe) which also exhibited low to no cytotoxicity and red blood cell haemolytic properties. The mechanisms of action of the 5-Br and 7-F analogues were attributed to the ability to disrupt the integrity of, and depolarize, bacterial membranes.
3-(7-Azaindolyl)-4-indolylmaleimides as a novel class of mutant isocitrate dehydrogenase-1 inhibitors: Design, synthesis, and biological evaluation
Hu, Yuanyuan,Gao, Anhui,Liao, Honghui,Zhang, Mengmeng,Xu, Gaoya,Gao, Lixin,Xu, Lei,Zhou, Yubo,Gao, Jianrong,Ye, Qing,Li, Jia
, (2018/09/06)
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.
Development of [18F]Maleimide-Based Glycogen Synthase Kinase-3β Ligands for Positron Emission Tomography Imaging
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
supporting information, p. 287 - 292 (2017/03/17)
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.
Use of indole compounds in radix isatidis, and derivatives thereof in preparation of anti-influenza virus medicines
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Paragraph 0542; 0544, (2017/09/21)
The invention discloses an application of indole compounds extracted from radix isatidis and represented by general formula (I), and derivatives and pharmaceutically acceptable salts thereof in the preparation of anti-influenza virus medicines or healthcare products, and discloses a preparation method of the compounds, and an application of medicinal compositions containing the compounds in the preparation of the anti-influenza virus medicines or healthcare products.
Indole compound with antivirus activity in radix isatidis and derivative of indole compound
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Paragraph 0544, (2017/09/29)
The invention discloses an indole compound extracted from radix isatidis shown in a general formula (I) and a derivative of the indole compound, as well as a salt acceptable on pharmacy, a preparation method of the compound, and a medicinal composite. The compound has apparent HIV-resisting activity and influenza virus-resisting activity, and can be used for preparing drugs or healthcare products for resisting HIV or influenza viruses. (The formula is shown in the description.).
Receptor binding profiles and quantitative structure-affinity relationships of some 5-substituted-N,N-diallyltryptamines
Cozzi, Nicholas V.,Daley, Paul F.
, p. 959 - 964 (2016/05/24)
N,N-Diallyltryptamine (DALT) and 5-methoxy-N,N-diallyltryptamine (5-MeO-DALT) are two tryptamines synthesized and tested by Alexander Shulgin. In self-experiments, 5-MeO-DALT was reported to be psychoactive in the 12-20 mg range, while the unsubstituted compound DALT had few discernible effects in the 42-80 mg range. Recently, 5-MeO-DALT has been used in nonmedical settings for its psychoactive effects, but these effects have been poorly characterized and little is known of its pharmacological properties. We extended the work of Shulgin by synthesizing additional 5-substituted-DALTs. We then compared them to DALT and 5-MeO-DALT for their binding affinities at 45 cloned receptors and transporter proteins. Based on in vitro binding affinity, we identified 27 potential receptor targets for the 5-substituted-DALT compounds. Five of the DALT compounds had affinity in the 10-80 nM range for serotonin 5-HT1Aand 5-HT2Breceptors, while the affinity of DALT itself at 5-HT1Areceptors was slightly lower at 100 nM. Among the 5-HT2subtypes, the weakest affinity was at 5-HT2Areceptors, spanning 250-730 nM. Five of the DALT compounds had affinity in the 50-400 nM range for serotonin 5-HT1D, 5-HT6, and 5-HT7receptors; again, it was the unsubstituted DALT that had the weakest affinity at all three subtypes. The test drugs had even weaker affinity for 5-HT1B, 5-HT1E, and 5-HT5Asubtypes and little or no affinity for the 5-HT3subtype. These compounds also had generally nanomolar affinities for adrenergic α2A, α2B, and α2Creceptors, sigma receptors σ1and σ2, histamine H1receptors, and norepinephrine and serotonin uptake transporters. They also bound to other targets in the nanomolar-to-low micromolar range. Based on these binding results, it is likely that multiple serotonin receptors, as well as several nonserotonergic sites are important for the psychoactive effects of DALT drugs. To learn whether any quantitative structure-affinity relationships existed, we evaluated correlations among physicochemical properties of the congeneric 5-substituted-DALT compounds. The descriptors included electronic (σp), hydrophobic (π), and steric (CMR) parameters. The binding affinity at 5-HT1A, 5-HT1D, 5-HT7, and κ opioid receptors was positively correlated with the steric volume parameter CMR. At α2A, α2B, and α2Creceptors, and at the histamine H1receptor, binding affinity was correlated with the Hammett substituent parameter σp; higher affinity was associated with larger σpvalues. At the σ2receptor, higher affinity was correlated with increasing π. These correlations should aid in the development of more potent and selective drugs within this family of compounds.
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
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
, p. 1179 - 1188 (2015/03/04)
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.
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
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
, p. 746 - 752 (2015/03/30)
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.
Breaking and Making of Rings: A Method for the Preparation of 4-Quinolone-3-carboxylic Acid Amides and the Expensive Drug Ivacaftor
Vasudevan,Jachak, Gorakhnath R.,Reddy, D. Srinivasa
supporting information, p. 7433 - 7437 (2016/01/25)
A simple and convenient method to access 4-quinolone-3-carboxylic acid amides from indole-3-acetic acid amides through one-pot oxidative cleavage of the indole ring followed by condensation (Witkop-Winterfeldt type oxidation) was explored. The scope of the method was confirmed with more than 20 examples and was successfully applied to the synthesis of the drug Ivacaftor, the most expensive drug on the market.
A facile synthesis of novel 3-(aryl/alkyl-2-ylmethyl)-2-thioxothiazolidin- 4-ones using microwave heating
Kamila, Sukanta,Ankati, Haribabu,Harry, Emily,Biehl, Edward R.
scheme or table, p. 2195 - 2198 (2012/05/20)
(Z)-5-(2-(1H-Indol-3-yl)-2-oxoethylidene)-3-(aryl/alkyl-2-ylmethyl) -2-thioxothiazolidin-4-ones (7a-w) have been synthesized by the Knoevenagel condensation reaction of 3-(aryl/alkyl-2-ylmethyl)-2-thioxothiazolidin-4-ones (3a-d) with suitably substituted 2-(1H-indol-3-yl)2-oxoacetaldehydes (6a-g) under microwave conditions. The thioxothiazolidin-4-ones were prepared from the corresponding aryl/alkyl amines (1a-d) and di-(carboxymethyl)-trithiocarbonyl (2). The aldehydes (6a-g) were synthesized from the corresponding acid chlorides (5a-g) using HsnBu3.
