- Efficient salt-induced kinase inhibitor and preparation method thereof
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The invention discloses an efficient salt-induced kinase inhibitor and a preparation method thereof, and the efficient salt-induced kinase inhibitor is characterized by comprising substances of a chemical formula in the invention. The salt-induced kinase inhibitor with excellent performance has high inhibitory activity for in-vitro experiments and also has high cell inhibitory activity.
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Paragraph 0136-0139
(2021/09/04)
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- Second-Generation Meridianin Analogues Inhibit the Formation of Mycobacterium smegmatis Biofilms and Sensitize Polymyxin-Resistant Gram-Negative Bacteria to Colistin
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Drug-resistant bacteria are rapidly becoming a significant problem across the globe. One element that factors into this crisis is the role played by bacterial biofilms in the recalcitrance of some infections to the effects of conventional antibiotics. Bacteria within a biofilm are highly tolerant of both antibiotic treatment and host immune responses. Biofilms are implicated in many chronic infections, including tuberculosis, in which they can act as bacterial reservoirs, requiring an arduous antibiotic regimen to eradicate the infection. A separate, compounding problem is that antibiotics once seen as last-resort drugs, such as the polymyxin colistin, are now seeing more frequent usage as resistance to front-line drugs in Gram-negative bacteria becomes more prevalent. The increased use of such antibiotics inevitably leads to an increased frequency of resistance. Drugs that inhibit biofilms and/or act as adjuvants to overcome resistance to existing antibiotics will potentially be an important component of future approaches to antibacterial treatment. We have previously demonstrated that analogues of the meridianin natural product family possess adjuvant and antibiofilm activities. In this study, we explore structural variation of the lead molecule from previous studies, and identify compounds showing both improved biofilm inhibition potency and synergy with colistin.
- Melander, Christian,Melander, Roberta J.,Zeiler, Michael J.
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supporting information
p. 1672 - 1679
(2020/08/05)
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- THIOINDIRUBINS
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Disclosed herein inter alia are compositions and methods for treating cancer using thioindirubin derivatives.
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Paragraph 0407-0409
(2019/03/17)
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- Facile synthesis of isatins by direct oxidation of indoles and 3-iodoindoles using NIS/IBX
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A facile one-pot access to a broad range of isatins by direct oxidation of indoles using NIS/IBX reagent in DMSO at 25 °C in very good isolated yields is reported. It is shown by mechanistic investigations that a number of substituted indoles react rapidly with NIS in DMSO to produce intermediary 3-iodoindoles, which undergo oxidation subsequently to isatins with IBX.
- Chandra, Ajeet,Yadav, Navin R.,Moorthy, Jarugu Narasimha
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supporting information
p. 2169 - 2174
(2019/03/04)
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- Mono-selective β-C-H arylation of: N -methylated amino acids and peptides promoted by the 2-(methylthio)aniline directing group
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2-(Methylthio)aniline (MTA) directed C(sp3)-H functionalisations are efficient and straightforward protocols for the selective β-modification of N-methylated amino acids. The decreased reactivity of MTA in comparison with the 8-aminoquinoline (AQ) directing group allows for selective monoarylations in high yields without the formation of side products. The protocol is also suitable for the introduction of highly functionalised side chains onto the C-terminal alanines of dipeptides. The MTA directing group can easily be removed, providing free carboxylic acids as valuable building blocks.
- Kinsinger, Thorsten,Kazmaier, Uli
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supporting information
p. 5595 - 5600
(2019/06/13)
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- Discovery and evaluation of 3,5-disubstituted indole derivatives as Pim kinase inhibitors
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Pim kinases are promising therapeutic targets for the treatment of hematological cancers. A potent Pim kinase inhibitor 7f, derived from meridianin C, was further optimized by the replacement of 2-aminopyrimidine with substituted benzene. The optimization of the C-3 and C-5 positions of indole yielded compound 43 with improved cellular potency and high selectivity against a panel of 14 different kinases.
- More, Kunal N.,Hong, Victor S.,Lee, Ahyeon,Park, Jongsung,Kim, Shin,Lee, Jinho
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supporting information
p. 2513 - 2517
(2018/06/06)
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- A Versatile C–H Halogenation Strategy for Indole Derivatives under Electrochemical Catalyst- and Oxidant-Free Conditions
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Halogenated indoles are essential structural motifs in bioactive natural products. Reported herein is an economical and scalable electrochemical protocol for regioselective 3C–H halogenation of indole derivatives. This strategy provides access to a host of 3-iodo-, 3-bromo-, 3-chloro-, and 3-thiocyanoindole derivatives under mild conditions using inexpensive (pseudo)halide salts as the sole reagent. The optimized conditions do not require any supplementary electrolyte salts.
- Sun, Linhao,Zhang, Xing,Li, Zilong,Ma, Jimei,Zeng, Zhen,Jiang, Hong
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supporting information
p. 4949 - 4952
(2018/05/15)
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- PhI(OAc)2/NaX-mediated halogenation providing access to valuable synthons 3-haloindole derivatives
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This paper describes a mild phenyliodine diacetate mediated method for selective chlorination, bromination, and iodination of indole C-H bonds using sodium halide as a source for analogous halogenations. The combination of NaX and phenyliodine diacetate provides an invincible system for halogenation of indoles. This protocol was compatible with a wide array of indole substrates and provides straight forward access to potential halogenated arenes.
- Himabindu, Vittam,Parvathaneni, Sai Prathima,Rao, Vaidya Jayathirtha
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p. 18889 - 18893
(2018/11/27)
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- Synthesis of furan-fused 1,4-dihydrocarbazoles via an unusual Garratt-Braverman Cyclization of indolyl propargyl ethers and their antifungal activity
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The reactivity of indole based bis-propargyl ethers 4a-4g under Garratt-Braverman condition (KOBut in refluxing toluene) has been studied. Interestingly, these propargyl systems with one arm attached with substituted 3-indolyl derivatives leavi
- Mandal, Arundhoti,Mandal, Santi M.,Jana, Saibal,Bag, Subhendu Sekhar,Das, Amit K.,Basak, Amit
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p. 3543 - 3556
(2018/05/25)
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- Structural Optimization and Pharmacological Evaluation of Inhibitors Targeting Dual-Specificity Tyrosine Phosphorylation-Regulated Kinases (DYRK) and CDC-like kinases (CLK) in Glioblastoma
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The DYRK family contains kinases that are up-regulated in malignancy and control several cancer hallmarks. To assess the anticancer potential of inhibitors targeting DYRK kinases, we developed a series of novel DYRK inhibitors based on the 7-azaindole scaffold. All compounds were tested for their ability to inhibit DYRK1A, DYRK1B, DYRK2, and the structurally related CLK1. The library was screened for anticancer efficacy in established and stem cell-like glioblastoma cell lines. The most potent inhibitors (IC50 ≤ 50 nM) significantly decreased viability, clonogenic survival, migration, and invasion of glioblastoma cells. Target engagement was confirmed with genetic knockdown and the cellular thermal shift assay. We demonstrate that DYRK1A’s thermal stability in cells is increased upon compound treatment, confirming binding in cells. In summary, we present synthesis, structure-activity relationship, and efficacy in glioblastoma-relevant models for a library of novel 7-azaindoles.
- Zhou, Qingqing,Phoa, Athena F.,Abbassi, Ramzi H.,Hoque, Monira,Reekie, Tristan A.,Font, Josep S.,Ryan, Renae M.,Stringer, Brett W.,Day, Bryan W.,Johns, Terrance G.,Munoz, Lenka,Kassiou, Michael
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p. 2052 - 2070
(2017/03/17)
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- Araf51 with improved transglycosylation activities: One engineered biocatalyst for one specific acceptor
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A random mutagenesis of the arabinofuranosyl hydrolase Araf51 has been run in order to have access to efficient biocatalysts for the synthesis of alkyl arabinofuranosides. The mutants were selected on their ability to catalyze the transglycosylation reaction of p-nitrophenyl α-l-arabinofuranoside (pNP-Araf) used as a donor and various aliphatic alcohols as acceptors. This screening strategy underlined 5 interesting clones, each one corresponding to one acceptor. They appeared to be much more efficient in the transglycosylation reaction compared to the wild type enzyme whereas no self-condensation or hydrolysis products could be detected. Moreover, the high specificity of the mutants toward the alcohols for which they have been selected validates the screening process. Sequence analysis of the mutated enzymes revealed that, despite their location far from the active site, the mutations affect significantly the kinetics properties as well as the substrate affinity of these mutants toward the alcohol acceptors in the transglycosylation reaction.
- Pennec, Alizé,Daniellou, Richard,Loyer, Pascal,Nugier-Chauvin, Caroline,Ferrières, Vincent
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supporting information
p. 50 - 55
(2015/02/19)
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- An iodine effect in ambipolar organic field-effect transistors based on indigo derivatives
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5,5′-Diiodoindigo (4) exhibits excellent ambipolar transistor properties with hole/electron mobilities of μh/μe = 0.42/0.85 cm2 V-1 s-1. The halogen substituted indigos show decreasing tilt angles from F to I in the crystals. In addition, the iodine-iodine interaction provides extraordinarily large interchain interaction. However, the X-ray diffraction suggests that the indigo molecules are arranged approximately perpendicular to the substrate in the thin films, probably due to the extra iodine-iodine interaction. The remarkable performance is ascribed to this characteristic supramolecular interaction.
- Pitayatanakul, Oratai,Iijima, Kodai,Ashizawa, Minoru,Kawamoto, Tadashi,Matsumoto, Hidetoshi,Mori, Takehiko
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supporting information
p. 8612 - 8617
(2015/08/24)
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- High performance ambipolar organic field-effect transistors based on indigo derivatives
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A bio-inspired organic semiconductor 5,5′-diphenylindigo shows excellent and well-balanced ambipolar transistor properties; its hole and electron mobilities are 0.56 and 0.95 cm2 V-1 s-1, respectively. The enhanced performance is attributed to the extended π-π overlap of the phenyl groups as well as the characteristic packing pattern that is a hybrid of the herringbone and brickwork structures. The ambipolar transistor characteristics are analyzed considering its operating regions, where a large unipolar saturated region appears due to the difference of the electron and hole threshold voltages.
- Pitayatanakul, Oratai,Higashino, Toshiki,Kadoya, Tomofumi,Tanaka, Masaki,Kojima, Hirotaka,Ashizawa, Minoru,Kawamoto, Tadashi,Matsumoto, Hidetoshi,Ishikawa, Ken,Mori, Takehiko
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supporting information
p. 9311 - 9317
(2015/01/09)
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- Araf51 with improved transglycosylation activities: One engineered biocatalyst for one specific acceptor
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A random mutagenesis of the arabinofuranosyl hydrolase Araf51 has been run in order to have access to efficient biocatalysts for the synthesis of alkyl arabinofuranosides. The mutants were selected on their ability to catalyze the transglycosylation reaction of p-nitrophenyl α-l-arabinofuranoside (pNP-Araf) used as a donor and various aliphatic alcohols as acceptors. This screening strategy underlined 5 interesting clones, each one corresponding to one acceptor. They appeared to be much more efficient in the transglycosylation reaction compared to the wild type enzyme whereas no self-condensation or hydrolysis products could be detected. Moreover, the high specificity of the mutants toward the alcohols for which they have been selected validates the screening process. Sequence analysis of the mutated enzymes revealed that, despite their location far from the active site, the mutations affect significantly the kinetics properties as well as the substrate affinity of these mutants toward the alcohol acceptors in the transglycosylation reaction.
- Pennec, Aliz,Daniellou, Richard,Loyer, Pascal,Nugier-Chauvin, Caroline,Ferrires, Vincent
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supporting information
p. 50 - 55
(2015/02/19)
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- One-pot synthesis of camalexins and 3,3′-biindoles by the Masuda borylation-Suzuki arylation (MBSA) sequence
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The Masuda borylation/Suzuki arylation (MBSA) sequence starting from N-protected 3-iodoindoles has successfully been extended to the coupling of five-membered heterocycles and indoles in the arylation step, which could not be achieved with previously developed MBSA methods. By this approach the one-pot nature of the method as well as the use of a simple catalyst system has been retained. The applicability of the method has been demonstrated by the facile synthesis of camalexins and 3,3′-biindoles, compounds of special interest due to their pronounced antifungal, antimicrobial and cytotoxic activities. The Masuda borylation/Suzuki arylation sequence furnishes in a concise one-pot manner camalexins and 3,3′-biindoles, compounds that show pronounced antifungal, antimicrobial, and cytotoxic activities. Copyright
- Tasch, Boris O. A.,Antovic, Dragutin,Merkul, Eugen,Mueller, Thomas J. J.
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supporting information
p. 4564 - 4569
(2013/07/26)
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- A convenient iodination of indoles and derivatives
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We report a direct iodination of indole and derivative compounds with iodine monochloride (ICl) in the presence of Celite. This procedure has now been extended to the iodination of substituted indoles, azaindoles and pyrroles. The scope of this procedure
- Hamri, Salha,Rodríguez, Jose,Basset, Joan,Guillaumet, Gérald,Dolors Pujol
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supporting information; experimental part
p. 6269 - 6275
(2012/08/28)
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- Synthesis of 2-(3-indolyl)-1,4-naphthoquinones using 3-iodoindoles
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The usefulness of 3-iodoindoles available for introduction of an indole unit is presented. The reaction of various halo-3-iodoindoles with 1,4-naphthoquinone gave the corresponding 2-(3-indolyl)-1,4-naphthoquinones in moderate yields. The 3-iodoindole was used for synthesis of a compound containing both naphthazarin and indole skeletons.
- Tanoue, Yasuhiro,Hamada, Moritsugu,Kai, Norihisa,Sakata, Kazunori,Hashimoto, Mamoru,Nagai, Takeshi
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p. 1195 - 1199
(2007/10/03)
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