214468-37-8Relevant articles and documents
Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity
Recio, Rocío,Lerena, Patricia,Pozo, Esther,Calderón-Monta?o, José Manuel,Burgos-Morón, Estefanía,López-Lázaro, Miguel,Valdivia, Victoria,Pernia Leal, Manuel,Mouillac, Bernard,Organero, Juan ángel,Khiar, Noureddine,Fernández, Inmaculada
, p. 10350 - 10370 (2021/07/28)
NK1R antagonists, investigated for the treatment of several pathologies, have shown encouraging results in the treatment of several cancers. In the present study, we report on the synthesis of carbohydrate-based NK1R antagonists and their evaluation as anticancer agents against a wide range of cancer cells. All of the prepared compounds, derived from either-arabinose, have shown high affinity and NK1R antagonistic activity with a broad-spectrum anticancer activity and an important selectivity, comparable to Cisplatin. This strategy has allowed us to identify the galactosyl derivative 14α , as an interesting hit exhibiting significant NK1R antagonist effect (kinact0.209 ± 0.103 μM) and high binding affinity for NK1R (IC50= 50.4 nM,Ki= 22.4 nM by measuring the displacement of [125I] SP from NK1R). Interestingly, this galactosyl derivative has shown marked selective cytotoxic activity against 12 different types of cancer cell lines.
ANTAGONISTS OF NK1 RECEPTORS DERIVED FROM CARBOHYDRATES, PRODUCTION METHOD AND MEDICAL USE
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, (2018/04/19)
The invention relates to a compound of general formula (I), and to the use thereof in medicine, or for the production of a medicament for the treatment of different diseases, preferably a cancer such as melanoma, lung carcinoma or breast cancer. For this purpose, the invention also relates to a pharmaceutical composition comprising said compound. In addition, the invention relates to a method for producing the compound of general formula (I).
Epimeric and amino disaccharide analogs as probes of an α-(1→6)mannosyltransferase involved in mycobacterial lipoarabinomannan biosynthesist
Tam, Pui Hang,Lowary, Todd L.
supporting information; experimental part, p. 181 - 192 (2010/04/06)
Mycobacterial lipoarabinomannan (LAM) is an important, immunologically active glycan found in the cell wall of mycobacteria, including the human pathogen Mycobacterium tuberculosis. At the core of LAM is a mannan domain comprised of α-(1→6)-linked-mannopyranose (Manp) residues. Previously, we and others have demonstrated that α-Manp-(1→6)- α-Manp disaccharides (e.g., Manp-(1→6)-α-ManpOctyl, 1) are the minimum acceptor substrates for enzymes involved in the assembly of the LAM mannan core. We report here the synthesis five epimeric and three amino analogs of 1, and their subsequent biochemical evaluation against an α-(1→6)-ManT activity present in a membrane preparation from M. smegmatis. Changing the manno- configuration of either residue of 1 to talo- or gluco- led to a reduction or loss of activity, thus confirming earlier work showing that the C-2 and C-4 hydroxyl groups of each monosaccharide were important for enzymatic recognition. Characterization of the products formed from these analogs was done using a combination of mass spectrometry and glycosidase digestion, and full substrate kinetics were also performed. The analogs in which the acceptor hydroxyl group had been replaced with an amino group were, as expected, not substrates for the enzyme, but were weak inhibitors. The Royal Society of Chemistry 2010.
Synthesis of a Blocked Tetrasaccharide Related to the Repeating Unit of the Antigen from Shigella dysenteriae Type 9 in the Form of Its Methyl (R)-Pyruvate Ester and 2-(Trimethylsilyl)Ethyl Glycoside
Roy, Samarpita,Roy, Nirmolendu
, p. 521 - 535 (2007/10/03)
Starting from D-mannose, D-galactose and D-glucosamine hydrochloride, two disaccharide blocks were synthesized. Schmidt's inverse addition technique of tricbloroacetimidate was utilized for the construction of a disaccharide with a β-mannosidic linkage in
Total synthesis and biological evaluation of glycolipids plakosides A, B, and their analogs
Nicolaou, Kyriacos C.,Li, Jim,Zenke, Gerhard
, p. 1977 - 2006 (2007/10/03)
The total synthesis of plakosides A (1) and B (2), and their designed analogs 3-10 was accomplished. The convergent strategy employed involved construction of the individual building blocks employing the Sharpless asymmetric dihydroxylation and the Charette asymmetric cyclopropanation reactions to introduce the desired configuration, followed by their couplings and final elaboration. Thus, key intermediates 12-14 were prepared in their optically active forms and joined through a glycosidation reaction and amide-bond formation to yield the target molecules after appropriate elaboration and final deprotection. The synthesized compounds 1-10 were evaluated for their immunosuppressive properties in vitro and found to be only modestly active.
A facile chemoselective deprotection of the p-methoxybenzyl group
Yu, Wensheng,Su, Mei,Gao, Xiaobang,Yang, Zhiqiang,Jin, Zhendong
, p. 4015 - 4017 (2007/10/03)
The p-methoxybenzyl (PMB) group can be chemoselectively cleaved at low temperature in the presence of SnCl4 and thiophenol. This method is especially useful in the cases where oxidative reagents such as DDQ and CAN need to be avoided. (C) 2000 Elsevier Science Ltd.
Use of acid-labile protective groups for carbohydrate moieties in synthesis of glycopeptides related to type II collagen
Broddefalk, Johan,Bergquist, Karl-Erik,Kihlberg, Jan
, p. 12047 - 12070 (2007/10/03)
β-D-Galactopyranosyl and α-D-glucopyranosyl-β-D-galactopyranosyl moieties carrying silyl, isopropylidene and 4-methoxybenzyl protective groups have been attached to the amino acid 5-hydroxy-L-norvaline. The resulting glycosylated building blocks were used in Fmoc solid-phase synthesis of glycopeptides related to a fragment from type II collagen which is immunodominant in a mouse model for rheumatoid arthritis. The protective groups used for the carbohydrate moieties were completely removed during acid catalyzed cleavage of the glycopeptides from the solid phase under conditions which left the O-glycosidic bonds intact.
