22860-91-9Relevant academic research and scientific papers
Substituted pyrazole compound, preparation method, pharmaceutical composition and applications thereof
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Paragraph 0378; 0386-0388, (2020/03/12)
The invention discloses a substituted pyrazole compound represented by a formula I, and a preparation method, a pharmaceutical composition and applications thereof, wherein the compound has characteristics of good stability, excellent solubility, low cytotoxicity and remarkable neuroprotective effect, can effectively prevent and treat nerve cell injury, and is an ideal medicinal compound for preventing or treating cerebral stroke, cerebral embolism, cerebral stroke sequelae, cerebral stroke dyskinesia, mitochondrial encephalomyopathy and amyotrophic lateral sclerosis of spinal cord.
Solasodine-3-O-β-D-glucopyranoside kills Candida albicans by disrupting the intracellular vacuole
Chang, Wenqiang,Li, Ying,Zhang, Ming,Zheng, Sha,Li, Yan,Lou, Hongxiang
, p. 139 - 146 (2017/06/05)
The increasing incidence of fungal infections and emergence of drug resistance underlie the constant search for new antifungal agents and exploration of their modes of action. The present study aimed to investigate the antifungal mechanisms of solasodine-3-O-β-D-glucopyranoside (SG) isolated from the medicinal plant Solanum nigrum L. In vitro, SG displayed potent fungicidal activity against both azole-sensitive and azole-resistant Candida albicans strains in Spider medium with its MICs of 32 μg/ml. Analysis of structure and bioactivity revealed that both the glucosyl residue and NH group were required for SG activity. Quantum dot (QD) assays demonstrated that the glucosyl moiety was critical for SG uptake into Candida cells, as further confirmed by glucose rescue experiments. Measurement of the fluorescence intensity of 2′,7'-dichlorofluorescin diacetate (DCFHDA) by flow cytometry indicated that SG even at 64 μg/ml just caused a moderate increase of reactive oxygen species (ROS) generation by 58% in C. albicans cells. Observation of vacuole staining by confocal microscopy demonstrated that SG alkalized the intracellular vacuole of C. albicans and caused hyper-permeability of the vacuole membrane, resulting in cell death. These results support the potential application of SG in fighting fungal infections and reveal a novel fungicidal mechanism.
Magnesium pyrophosphates in enzyme mimics of nucleotide synthases and kinases and in their prebiotic chemistry
Gopinath, Purushothaman,Ramalingam, Vijayakumar,Breslow, Ronald
, p. 12011 - 12014 (2015/10/12)
Derivatives of ribosyl pyrophosphate have been synthesized, and examined with magnesium salts in the coupling of the ribose unit to various nucleophiles, including pyrazole and 2-chloroimidazole. Only with the magnesium salt present did they generate the ribosyl cation by binding to the leaving group and then couple the ribose derivative with nucleophiles. The role of magnesium salts in phosphorylation of methanol by ATP was also examined. Here a remarkable effect was seen: phosphorylation by ATP was slowed with low concentrations of Mg2+ but accelerated by higher concentrations. Related effects were also seen in the effect of Mg2+ on phosphorylation by ADP. The likely mechanisms explain these effects.
Gold(III)-catalyzed glycosidations for 1,2- trans and 1,2- cis furanosides
Thadke, Shivaji A.,Mishra, Bijoyananda,Hotha, Srinivas
, p. 7358 - 7371 (2014/09/29)
Stereoselective synthesis of furanosides is still a daunting task, unlike the pyranosides, for which several methods exist. Herein, a unified stereoselective strategy for the synthesis of 1,2-trans and 1,2-cis furanosides is revealed for seven out of eight possible isomers of pentoses. The identified protocol gives access to diastereoselective synthesis of α- and β-araf, ribf, lyxf, and α-xylf furanosides. 1,2-trans glycosides were synthesized by the use of propargyl 1,2-orthoesters under gold-catalyzed glycosidation conditions, and subsequently, they are converted into 1,2-cis glycosides through oxidation-reduction as the key functional group transformation. All the reactions are found to be fully diastereoselective, mild, and high yielding.
Facile synthesis of β- And α-arabinofuranosides and application to cell wall motifs of M. tuberculosis
Thadke, Shivaji A.,Mishra, Bijoyananda,Hotha, Srinivas
supporting information, p. 2466 - 2469 (2013/06/27)
Propargyl 1,2-orthoesters of arabinose are exploited for the synthesis of 1,2-trans furanosides; easily accessible 1,2-trans ribofuranosides are converted to challenging 1,2-cis-arabinofuranosides by oxidoreduction. Utility of these protocols was demonstrated by the successful synthesis of major structural motifs present in the cell surface of Mycobacterium tuberculosis. Key furanosylations were carried out under gold-catalyzed glycosidation conditions.
A facile synthetic route to diazepinone derivatives via ring closing metathesis and its application for human cytidine deaminase inhibitors
Kim, Minkyoung,Gajulapati, Kondaji,Kim, Chorong,Jung, Hwa Young,Goo, Jail,Lee, Kyeong,Kaur, Navneet,Kang, Hyo Jin,Chung, Sang J.,Choi, Yongseok
supporting information, p. 11443 - 11445 (2013/01/15)
A variety of diazepinone derivatives were prepared from α-amino acids and amino alcohols by a new synthetic methodology based on ring closing metathesis as a key step. The diazepinones were coupled with ribose derivatives to afford novel diazepinone nucleosides. Among them, (4R)-1-ribosyl-4-methyl-3, 4-dihydro-1H-1,3-diazepin-2(7H)-one (3) showed a potent inhibitory effect (Ki = 145.97 ± 4.87 nM) against human cytidine deaminase.
Ready preparation of furanosyl n-pentenyl orthoesters from corresponding methyl furanosides
Ramamurty, Changalvala V. S.,Ganney, Parimala,Rao, C. Srinivas,Fraser-Reid, Bert
supporting information; experimental part, p. 2245 - 2247 (2011/05/17)
The 3,5-di-O-benzoyl n-pentenyl orthoesters of the four pentofuranoses have been prepared. The first key intermediate in each case is the methyl pentofuranoside(s), and a user-friendly procedure for the preparation of each, based on the Callam-Lowary precedent, is described, whereby formation of the crucial α/β anomeric mixture is optimized. The mixture is used directly to prepare the corresponding perbenzoylated pentofuranosyl bromide(s) and then the title compounds.
Synthesis and biological evaluation of phloridzin analogs as human concentrative nucleoside transporter 3 (hCNT3) inhibitors
Gupte, Amol,Buolamwini, John K.
supporting information; experimental part, p. 917 - 921 (2009/09/06)
Nucleoside transporter inhibitors have potential therapeutic applications as anticancer, antiviral, cardioprotective and neuroprotective agents. Although quite a few potent inhibitors of the equilibrative nucleoside transporters are known, largely missing are the concentrative nucleoside transporter inhibitors. Phloridzin (3, Ki = 16.00 μM) is a known moderate inhibitor of the concentrative nucleoside transporters. We have synthesized and evaluated analogs of phloridzin at the hCNT3 nucleoside transporter. Within the series of synthesized analogs compound 16 (Ki = 2.88 μM), possessing a ribofuranose sugar unit instead of a glucopyranose as present in phloridzin, exhibited the highest binding affinity at the hCNT3 transporter. Phloridzin and compound 16 have also been shown to be selective for the hCNT3 transporter as compared with the hENT1 transporter. Compound 16 can serve as a new lead which after further modifications could yield selective and potent hCNT3 inhibitors.
Chemical investigations in the synthesis of O-serinyl aminoribosides
Ginisty, Maryon,Gravier-Pelletier, Christine,Le Merrer, Yves
, p. 142 - 150 (2007/10/03)
Glycosylation involving d-ribose derivatives and various N-protected tert-butyl l-serinates can be achieved efficiently by careful choice of the activation method at the anomeric position and of the Lewis acid promoter. The conditions described allow the major formation of the β-anomer required for further elaboration to liposidomycin and caprazamycin analogues.
A versatile scaffold for a library of liposidomycins analogues: A crucial and potent glycosylation step
Gravier-Pelletier, Christine,Ginisty, Maryon,Le Merrer, Yves
, p. 189 - 193 (2007/10/03)
A key step for the synthesis of a diazepanone scaffold dedicated to a library of MraY inhibitors is described. It involves the O-glycosylation of a conveniently protected L-serine by a D-ribofuranose derivative. High yield and selectivity were obtained.
