770-12-7Relevant articles and documents
Prodrug compound and application ofprodrug compound in treatment of cancer
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Paragraph 0140-0141, (2021/03/06)
The present invention provides a compound indicated by a formula (I), pharmaceutically acceptable salts or esters thereof, a pharmaceutical composition of the compound, and application of the compoundand the pharmaceutical composition in the inhibition or regulation of the activity of tyrosine kinase and treating disease symptoms or symptoms including cancer mediated by tyrosine kinase.
PRODRUGS OF THE TYROSINE KINASE INHIBITOR FOR TREATING CANCER
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Paragraph 00101-00102, (2021/03/05)
There are provided compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions thereof, useful for inhibition or modulation of the activity of tyrosine kinases and treatment of disease states or conditions mediated by tyrosine kinases, including cancers. (I)
Organophosphorous phenyl phosphates: Synthesis, dye/protein interactions and antimicrobial evaluation
Ameta, Rakesh Kumar,Duan, Yongtao,Koshti, Rohit R.,Muddassir, Mohd.,Patel, Amee S.,Trivedi, Nidhi S.,Vyas, Akshay
, (2021/01/09)
A series of Phenyl Phosphates (PPs) has been synthesized and characterized with FTIR spectroscopy. PPs, the product of the reaction of phenol and phosphoryl chloride followed by hydrolysis having larger number of hydrophilic hydroxyl groups, used for the dye interaction and antimicrobial activities. Interaction of PPs with 1,2-diphenyldiazene and 4-(phenyldiazene)phenol were studied through UV/ Vis method where observed hypochromic effect has revealed the dye adsorption property of PPs. Similarly PPs have shown the interaction with bovine serum and human serum albumins where the weaker interaction observed with later. Antimicrobial in vitro evaluation has been assessed on the basis of zone of inhibition with six bacterial (gram +ve and –ve) strains. Since PPs were found very active so minimal inhibitory concentration (MIC) analysis was done where all PPs have shown MIC less than 5 μg/mL. Due to high number of hydroxyl groups PPs have shown good interactions with biomolecules and cell wall of bacteria therefore this impression has predicted their future in medicinal field.
BI- AND MONOCYCLIC NUCLEOSIDE ANALOGS FOR TREATMENT OF HEPATITIS E
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Page/Page column 35; 43, (2021/10/22)
The present disclosure is directed toward bi- and monocyclic nucleoside analogs, and compositions comprising these compounds for use in the treatment of hepatitis E infections.
Preparation method of pentaerythritol diphosphate
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Paragraph 0032; 0044-0045; 0047-0048; 0050-0051, (2020/09/12)
The invention relates to the technical field of organic synthesis, and provides a preparation method of pentaerythritol diphosphate. The phosphoryl dichloride compound is prepared from a phenolic compound and phosphorus oxychloride under the condition of a catalyst, the yield of the phosphoryl dichloride compound is high, the activity of the phosphoryl dichloride compound is high, and the next step of reaction can be directly carried out without drying; then the phosphoryl dichloride compound is reactd with pentaerythritol under the vacuum pressure reduction condition, acid generated in the reaction can be rapidly removed under the vacuum pressure reduction condition, and the reaction can be carried out in the forward direction; furthermore, a phosphoryl dichloride compound is dropwise added, after dropwise adding is completed, esterification can be completed basically by one acyl chloride, and at the moment, an acid-binding agent is added, so that esterification of a second acyl chloride is facilitated, and the reaction time is greatly shortened; and the reaction temperature can be reduced under the vacuum decompression condition, the problems of acidolysis of pentaerythritol diphosphate and reaction with hydrogen chloride are avoided, the reaction safety and operability are improved, and the reaction efficiency is improved.
A Phosphoramidate Strategy Enables Membrane Permeability of a Non-nucleotide Inhibitor of the Prolyl Isomerase Pin1
Schwarz, Daniel M. C.,Williams, Sarah K.,Dillenburg, Maxwell,Wagner, Carston R.,Gestwicki, Jason E.
supporting information, p. 1704 - 1710 (2020/09/02)
The membrane permeability of nucleotide-based drugs, such as sofosbuvir (Sovaldi), requires installation of phosphate-caging groups. One strategy, termed "ProTide", masks the anionic phosphate through an N-linked amino ester and an O-linked aromatic phospho-ester, such that release of the active drug requires consecutive enzymatic liberation by an esterase and then a phosphoramidase, such as Hint1. Because Hint1 is known to be selective for nucleotides, it was not clear if the ProTide approach could be deployed for non-nucleotides. Here, we demonstrate that caging of a phosphate-containing inhibitor of the prolyl isomerase Pin1 increases its permeability. Moreover, this compound was processed by both esterase and phosphoramidase activity, releasing the active molecule to bind and inhibit Pin1 in cells. Thus, Hint1 appears to recognize a broader set of substrates than previously appreciated. It seems possible that other potent, but impermeable, phosphate-containing inhibitors might likewise benefit from this approach.
Compound for treating metabolic diseases as well as preparation method and application thereof
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Paragraph 0170-0173, (2019/07/04)
The invention provides a compound for treating metabolic diseases, the compound has a structure represented by formula (I) or formula (II), or a racemate, a stereoisomer, a geometric isomer, a tautomer, a solvate, a hydrate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. The compounds provided by the invention are FXR and/or TGR5 receptor activators, and the compounds havethe activity of activating FXR and/or TGR5 receptors, and can be used for preparing medicines for treating chronic liver diseases, metabolic diseases or portal hypertension.
Polyfluoroaromatic stavudine (d4T) ProTides exhibit enhanced anti-HIV activity
Kandil, Sahar,Pannecouque, Christophe,Chapman, Fiona M.,Westwell, Andrew D.,McGuigan, Christopher
supporting information, (2019/11/13)
Human Immunodeficiency Virus (HIV) damages the immune system and leads to the life-threatening acquired immunodeficiency syndrome (AIDS). Despite the advances in the field of antiretroviral treatment, HIV remains a major public health challenge. Nucleosides represent a prominent chemotherapeutic class for treating viruses, however their cellular uptake, kinase-mediated activation and catabolism are limiting factors. Herein, we report the synthesis and in vitro evaluation of stavudine (d4T) ProTides containing polyfluorinated aryl groups against two strains; HIV-1 (IIIB) and HIV-2 (ROD). ProTide 5d containing a meta-substituted pentafluorosulfanyl (3-SF5) aryl group showed superior antiviral activity over the parent d4T and the nonfluorinated analogue 5a. ProTide 5d has low nanomolar antiviral activity; (IC50 = 30 nM, HIV-1) and (IC50 = 36 nM, HIV-2) which is over tenfold more potent than d4T. Interestingly, ProTide 5d showed a significantly high selectivity indices with SI = 1753 (HIV-1) and 1461 (HIV-2) which is more than twice that of the d4T. All ProTides were screened in wild type as well as thymidine kinase deficient (TK?) cells. Enzymatic activation of ProTide 5d using carboxypeptidase Y enzyme and monitored using both 31P and 19F NMR is presented.
NUCLEOSIDE PHOSPHATE COMPOUND AND PREPARATION METHOD AND USE THEREOF
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Paragraph 0178-0179; 0182-0183, (2019/11/14)
Provided in the present invention are a compound of Formula (I), a pharmaceutical composition comprising the same, a method for preparing the same, and use thereof as a NS5B polymerase inhibitor, a DNA polymerase inhibitor or a reverse transcriptase inhibitor for the prevention or treatment of viral diseases or cancers.
Exploration of chiral Lewis acid Mg2+ catalysts in the synthesis of aryl organophosphate triesters from phosphorus oxychloride through a three-step, two-pot substitution sequence
Granger, Emily,Solomianko, Katarzyna,Young, Cori,Erb, Jeremy
supporting information, p. 1404 - 1408 (2018/03/13)
A variety of nucleophilic and Lewis acid catalysts were examined for use in promoting the synthesis of organophosphate triesters. Eight novel organophosphate triesters are reported here for the first time. MgSO4 was discovered as an inexpensive catalyst capable of improving the synthesis of a variety of aryl organophosphate triesters from the readily available and low cost precursor phosphorus oxychloride in a three-step, two-pot sequence. Yields for this method improve upon the uncatalyzed method by 8–36%. Several chiral catalysts were tested, but none were able to induce enantioselectivity in the reaction.
