1036204-60-0Relevant articles and documents
Assembly of [2]Rotaxanes in Water
Aeschi, Yves,Drayss-Orth, Sylvie,Valá?ek, Michal,Raps, Felix,H?ussinger, Daniel,Mayor, Marcel
, p. 4091 - 4103 (2017)
Two [2]rotaxanes have been assembled in water from modular subunits through CuI-catalyzed azide–alkyne “click” chemistry. For this purpose, 2,6-disubstituted naphthalene axles with solubilizing oligo(ethylene glycol) (OEG) chains (n = 1–5) and propargyl terminal groups were synthesized and examined for their propensity to form inclusion complexes with a dicationic Diederich-type cyclophane host. The dependence of pseudorotaxane formation on the linkers between the naphthalene core and OEG chains, and in the case of ester linkers on different spacer lengths, was analyzed by titration experiments. In addition, the inclusion complexes of two [2]rotaxanes were trapped by using a water-soluble azide-functionalized stopper. Repetitive chromatography finally enabled the isolation of both mechanically interlocked [2]rotaxanes.
S-ANTIGEN TRANSPORT INHIBITING OLIGONUCLEOTIDE POLYMERS AND METHODS
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Paragraph 0061; 0392, (2021/06/22)
Various embodiments provide STOPS? polymers that are S-antigen transport inhibiting oligonucleotide polymers, processes for making them and methods of using them to treat diseases and conditions. In some embodiments the STOPS? modified oligonucleotides include an at least partially phosphorothioated sequence of alternating A and C units having modifications as described herein. The sequence independent antiviral activity against hepatitis B of embodiments of STOPS? modified oligonucleotides, as determined by HBsAg Secretion Assay, is an EC50 that is less than 100 nM.
The design, synthesis and anti-tumor mechanism study of new androgen receptor degrader
Xie, Hang,Liang, Jian-Jia,Wang, Ya-Lei,Hu, Tian-Xing,Wang, Jin-Yi,Yang, Rui-Hua,Yan, Jun-Ke,Zhang, Qiu-Rong,Xu, Xia,Liu, Hong-Min,Ke, Yu
, (2020/07/31)
Targeted protein degradation using small molecules is a novel strategy for drug development. In order to solve the problem of drug resistance in the treatment of prostate cancer, proteolysis-targeting chimeras (PROTAC) was introduced into the design of anti-prostate cancer derivatives. In this work, we synthesized two series of selective androgen receptor degraders (SARDs) containing the hydrophobic degrons with different linker, and then investigated the structure-activity relationships of these hybrid compounds. Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Among them, compound A9 displayed potent inhibitory activity against LNCaP prostate cancer cell line with IC50 values of 1.75 μM, as well as excellent AR degradation activity. Primary mechanism studies elucidated compound A9 arrested cell cycle at G0/G1 phase and induced a mild apoptotic response in LNCaP cells. Further study indicated that the degradation of AR was mediated through proteasome-mediated process. For all these reasons, compound A9 held promising potential as anti-proliferative agent for the development of highly efficient SARDs for drug-resistance prostate cancer therapies.
RAF-DEGRADING CONJUGATE COMPOUNDS
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Paragraph 0209; 0375-0376; 0388, (2018/11/22)
The present disclosure provides, inter alia, RAF-Degrading Conjugate Compounds that are useful in the treatment of cancer and other RAF related diseases. Also provided are, pharmaceutical compositions, methods of treatment, and kits comprising a RAF- Degrading Conjugate Compound.
Compounds and methods for inhibiting phosphate transport
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Page/Page column 562, (2016/05/02)
Compounds having activity as phosphate transport inhibitors, more specifically, inhibitors of intestinal apical membrane Na/phosphate co-transport, are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein X, Y, A, R1 and R2 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
A modular approach to triazole-containing chemical inducers of dimerisation for yeast three-hybrid screening
Tran, Fanny,Odell, Anahi V.,Ward, Gary E.,Westwood, Nicholas J.
supporting information, p. 11639 - 11657 (2013/10/22)
The yeast three-hybrid (Y3H) approach shows considerable promise for the unbiased identification of novel small molecule-protein interactions. In recent years, it has been successfully used to link a number of bioactive molecules to novel protein binding partners. However despite its potential importance as a protein target identification method, the Y3H technique has not yet been widely adopted, in part due to the challenges associated with the synthesis of the complex chemical inducers of dimerisation (CIDs). The development of a modular approach using potentially "off the shelf" synthetic components was achieved and allowed the synthesis of a family of four triazole-containing CIDs, MTX-Cmpd2.2-2.5. These CIDs were then compared using the Y3H approach with three of them giving a strong positive interaction with a known target of compound 2, TgCDPK1. These results showed that the modular nature of our synthetic strategy may help to overcome the challenges currently encountered with CID synthesis and should contribute to the Y3H approach reaching its full potential as an unbiased target identification strategy.
Synthesis of multivalent glycoclusters from 1-thio-β-D-galactose and their inhibitory activity against the β-galactosidase from E. coli
Cagnoni, Alejandro J.,Varela, Oscar,Gouin, Sebastien G.,Kovensky, Jose,Uhrig, Maria Laura
experimental part, p. 3064 - 3077 (2011/06/21)
The synthesis of multivalent glycoclusters, designed to be compatible with biological systems, is reported. A variety of 1-thio-β-d-galactosides linked to a terminal triple bond through oligoethyleneglycol chains of variable lengths has been synthesized. Also, azide-containing oligosaccharide scaffolds were prepared from trehalose, maltose, and maltotriose by direct azidation with NaN3/PPh3/CBr4. Click reaction between the thiogalactoside residues and the azide scaffolds under microwave irradiation afforded a family of glycoclusters containing 1 to 4 residues of 1-thio-β-D-galactose. The yields went from moderate to excellent, depending on the valency of the desired product. Deacetylation with Et 3N/MeOH/H2O led to the final products. Complete characterization of the products was performed by NMR spectroscopy and HR-MS techniques. Their activities as inhibitors of β-galactosidase from E. coli were determined by using the Lineweaver-Burk method. The use of hydrophilic carbohydrate scaffolds for the synthesis of multivalent galactosides represents an interesting approach to improve their pharmacokinetics and bioavailability. In addition, the presence of the thioglycosidic bond will improve their stability in biological fluids.
Multivalent iminosugars to modulate affinity and selectivity for glycosidases
Diot, Jennifer,Garcia-Moreno, M. Isabel,Gouin, Sebastien G.,Mellet, Carmen Ortiz,Haupt, Karsten,Kovensky, Jose
experimental part, p. 357 - 363 (2009/03/11)
A series of mono-, di- and tri-valent iminosugars based on oligoethylene scaffolds and N-substituted deoxynojirymicin epitopes have been synthesized by "click chemistry" to study the effect of multivalency on glycosidase inhibition. Biological evaluation evidenced differences in the inhibition trends as a function of the enzyme nature. The results demonstrate that multivalency can be used in some case to modulate both the affinity and the selectivity of glycosidase inhibition.
Synthesis of fluorescent probes based on stilbenes and diphenylacetylenes targeting β-amyloid plaques
Parhi, Ajit K.,Kung, Mei-Ping,Ploessl, Karl,Kung, Hank F.
, p. 3395 - 3399 (2008/09/21)
Three fluorescent probes were synthesized aiming for optical imaging to detect amyloid plaques present in the patients with Alzheimer's disease (AD). These compounds were prepared via Sonogashira coupling of a well-defined fluorophore (4-bora-3a,4a-diaza-
