5405-42-5Relevant articles and documents
NMDAR INHIBITING AGENTS AND GABAAR POTENTIATING AGENTS AND USES THEREOF
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Paragraph 0157, (2021/04/30)
N-methyl-d-aspartate receptors (NMDAR) and/or potentiating y-aminobutyric acid receptors (GABAAR) agents and uses thereof are described. Uses of these agents include methods of treating or preventing various psychiatric diseases, disorders, or conditions and methods of treating or preventing alcohol use disorder in a subject in need thereof.
Green Esterification of Carboxylic Acids Promoted by tert-Butyl Nitrite
Cheng, Xionglve,Jiang, Gangzhong,Li, Xingxing,Tao, Suyan,Wan, Xiaobing,Zhao, Yanwei,Zheng, Yonggao
supporting information, p. 2713 - 2718 (2021/06/25)
In this work, the green esterification of carboxylic acids promoted by tert-butyl nitrite has been well developed. This transformation is compatible with a broad range of substrates and exhibits excellent functional group tolerance. Various drugs and substituted amino acids are applicable to this reaction under near neutral conditions, with good to excellent yields.
Synthesis and anticancer activity of hybrid molecules based on lithocholic and (5Z,9Z)-tetradeca-5,9-dienedioic acids linked via mono(di,tri,tetra)ethylene glycol and α,ω-diaminoalkane units
D’yakonov, Vladimir A.,Tuktarova, Regina A.,Dzhemileva, Lilya U.,Ishmukhametova, Svetlana R.,Dzhemilev, Usein M.
, p. 1 - 29 (2021/02/09)
For the first time, hybrid molecules were synthesized on the basis of lithocholic and (5Z,9Z)- 1,14-tetradeca-5,9-dienedicarboxylic acids, obtained in two stages using the homo-cyclomagnesiation reaction of 2-(hepta-5,6-diene-1-yloxy)tetrahydro-2H-pyran at the key stage. The resulting hybrid molecules containing 5Z,9Z-dienoic acids are of interest as novel synthetic biologically active precursors to create modern drugs for the treatment of human oncological diseases. The synthesized hybrid molecules were found to exhibit extremely high in vitro inhibitory activity against human topoisomerase I, which is 2-4 times higher than that of camptothecin, a known topoisomerase I inhibitor. Using flow cytometry and fluorescence microscopy, it was first shown that these new molecules are efficient apoptosis inducers in HeLa, U937, Jurkat, K562, and Hek293 cell cultures. In addition, the results of investigations into the effect of the synthesized acids on mitochondria and studies of possible DNA damage in Jurkat tumor cells are also presented.
Aza-Matteson Reactions via Controlled Mono-and Double-Methylene Insertions into Nitrogen-Boron Bonds
Xie, Qiqiang,Dong, Guangbin
supporting information, p. 14422 - 14427 (2021/09/29)
Boron-homologation reactions represent an efficient and programmable approach to prepare alkylboronates, which are valuable and versatile synthetic intermediates. The typical boron-homologation reaction, also known as the Matteson reaction, involves formal carbenoid insertions into C-B bonds. Here we report the development of aza-Matteson reactions via carbenoid insertions into the N-B bonds of aminoboranes. By changing the leaving groups of the carbenoids and altering Lewis acid activators, selective mono- and double-methylene insertions can be realized to access various α- and β-boron-substituted tertiary amines, respectively, from common secondary amines. The derivatization of complex amine-containing bioactive molecules, diverse functionalization of the boronate products, and sequential insertions of different carbenoids have also been achieved.
COMPOSITIONS AND METHODS FOR PROFILING OF GUT MICROBIOTA-ASSOCIATED BILE SALT HYDROLASE (BSH) ACTIVITY
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Paragraph 0107-0109, (2021/10/22)
A composition having the following structure: wherein: R1 is OH, ester group, ether group, amine, thiol, thioether, halide, or a group containing an alkynyl or azido functionality; R2 is H, OH, ester group, ether group, amine, thiol, thioether, halide, or a group containing an alkynyl or azido functionality; R3 is a group containing a reactive functionality capable of covalent binding to a thiol or amine; and R4 is H, OH, ester group, ether group, amine, thiol, thioether, halide, or a group containing an alkynyl or azido functionality; wherein one of R1, R2 and R4 is a group containing an alkynyl or azido functionality. Also disclosed is a method for profiling changes in BSH enzyme activity by attaching active BSH enzymes in a sample to the probe shown above, attaching a tag to the probe, and detecting the active BSH enzymes to obtain an activity profile.
Preparation method of lithocholic acid and intermediates thereof
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, (2021/02/20)
The invention discloses a synthesis method of lithocholic acid and an intermediates thereof. According to the preparation method of the lithocholic acid intermediate, a compound I reacts with hydrogento generate a compound II in a mixed solvent by taking palladium on carbon as a catalyst and adding specific alkali; a low-price botanical bulk fermentation product BA is used as a raw material, andlithocholic acid is synthesized through side chain construction, hydrogenation, reduction, hydrolysis and other reactions; and the selectivity of 5beta hydrogen in the hydrogenation reaction is improved, high-toxicity reagents such as hydrazine hydrate are prevented from being used for hydroxyl due to removal of other animal-derived cholic acids, and the method is environmentally friendly, high insafety, simple in route, mild in reaction condition and suitable for industrial mass production.
Membrane transport inspired hydrolysis of non-activated esters at near physiological pH
Mandal, Raki,Mahanty, Kingshuk,Mandal, Subhendu,De Sarkar, Suman,Tarafdar, Pradip K.
supporting information, p. 11088 - 11091 (2021/10/30)
A positively charged micelle loaded with substrates was transported selectively to the reaction site (cathode) to promote the proximity and localization of the reactants (ester and hydroxide). The guided vehicular delivery coupled with electrolysis allows the hydrolysis of non-activated esters at near physiological pH with significant yields along with recyclability.
Optimization of EphA2 antagonists based on a lithocholic acid core led to the identification of UniPR505, a new 3α-carbamoyloxy derivative with antiangiogenetic properties
Incerti, Matteo,Russo, Simonetta,Corrado, Miriam,Giorgio, Carmine,Ballabeni, Vigilio,Chiodelli, Paola,Rusnati, Marco,Scalvini, Laura,Callegari, Donatella,Castelli, Riccardo,Vacondio, Federica,Ferlenghi, Francesca,Tognolini, Massimiliano,Lodola, Alessio
, (2020/01/29)
The EphA2 receptor has been validated in animal models as new target for treating tumors depending on angiogenesis and vasculogenic mimicry. In the present work, we extended our current knowledge on structure-activity relationship (SAR) data of two related classes of antagonists of the EphA2 receptor, namely 5β-cholan-24-oic acids and 5β-cholan-24-oyl L-β-homotryptophan conjugates, with the aim to develop new antiangiogenic compounds able to efficiently prevent the formation of blood vessels. As a result of our exploration, we identified UniPR505, N-[3α-(Ethylcarbamoyl)oxy-5β-cholan-24-oyl]-L-β-homo-tryptophan (compound 14), as a submicromolar antagonist of the EphA2 receptor capable to block EphA2 phosphorylation and to inhibit neovascularization in a chorioallantoic membrane (CAM) assay.
Synthesis of novel dimeric compounds containing triazole using click method and their selective antiproliferative and proapoptotic potential via mitochondrial apoptosis signaling
Karabulut, H. R. Ferhat,Karatavuk, Ali Osman,Ozyildirim, Hasan,Do?anlar, O?uzhan,Do?anlar, Zeynep Banu
, p. 643 - 655 (2020/01/31)
In this study, the main aim was synthesis of dimeric compounds, which contain lithocholic acid and a triazole structure to investigate the selective cellular and molecular antiproliferative and proapoptotic potential of these products in healthy embryonic fibroblast (MEF), cervix cancer (HeLa), and breast cancer (MCF-7) cells. Four ester (5a–d) and five dimeric (6a–d, 7) out of nine novel compounds were obtained. First of all, lithocholic acid was converted to methyl lithocholate and then it was reacted with certain alkynoic acids (a–d) to obtain its alkynoate derivatives (5a–d). Finally, these compounds were converted to dimers (6a–d) by using 2,6-bis(azidomethyl)pyridine via the click method. Our result indicate that, treatment with dimeric compounds can selectively decrease the cell viability and proliferation in cervix cancer HeLa and breast cancer MCF-7 cells, except 7 which caused a strong cytotoxicity on healthy MEF cells. According to MTT assay, Nucblue cell stain and Annexin V/Propodium iodide molecular probe staining, 100 μM concentrations of the dimeric compounds was sufficient in inducing death and apoptotic cell ratio in HeLa and MCF-7 breast cancer cells selectively. In brief, the present study indicates that most effective dimeric compounds are 6a and 6b, which have the highest IC50 (345.8–342.6 μM) value on healthy cell and the lowest IC50 value in both cervix (49.2–36.9 μM) and breast (23.0–66.1 μM) cancer cells especially long-term treatment and which triggers apoptosis pathway specifically.
Synthesis of new cisplatin derivatives from bile acids
?otowski, Zenon,Hryniewicka, Agnieszka,Morzycki, Jacek W.,Rárová, Lucie,Seroka, Barbara,Sicinski, Rafal R.,Tomkiel, Aneta M.
, (2020/02/18)
A series of bile acid derived 1,2- and 1,3-diamines as well as their platinum(II) complexes were designed and synthesized in hope to get a highly cytotoxic compound by the combination of two bioactive moieties. All complexes obtained were subjected to cytotoxicity assays in vitro and some hybrid molecules showed an expected activity.
