- Prodrug compound and application ofprodrug compound in treatment of cancer
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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.
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- Nucleotide derivative and pharmaceutical composition and application thereof
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The invention discloses a nucleotide derivative and a pharmaceutical composition and application thereof, wherein the nucleotide derivative is as shown in a formula (I). The compound can be used for preparing anti-virus infection drugs.
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- PRODRUGS OF THE TYROSINE KINASE INHIBITOR FOR TREATING CANCER
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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)
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Paragraph 00134-00135
(2021/03/05)
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- Method for preparing sofosbuvir intermediate by using microfluid reaction device
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The invention discloses a method for preparing a sofosbuvir intermediate by using a microfluid reaction device. The method comprises the following steps: pumping phenyl dichlorophosphate and pentafluorophenol into a first micro-channel reactor, carrying o
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Paragraph 0046-0054
(2020/04/17)
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- THIARABINE- AND THIARABINE PRODRUG-BASED TREATMENTS
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The present disclosure is concerned with combination therapies that include sulfur- based nucleotide and nucleoside compounds for the treatment of various cancers such as, for example, sarcomas, carcinomas, hematological cancers, solid tumors, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, bladder cancer, thyroid cancer, testicular cancer, pancreatic cancer, endometrial cancer, melanomas, gliomas, leukemias, lymphomas, chronic myeloproliferative disorders, myelodysplastic syndromes, myeloproliferative neoplasms, and plasma cell neoplasms (myelomas). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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- A preparation process of rope non-cloth wei improved method
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The invention provides a method for improving technique of rope non-cloth wei, for the oxidation of olefinic bond when [...], the oxidizing agent is potassium permanganate into sodium permanganate, product yield from 78% improved to 90% or more; in cytosine with halo ethylthio butt coupling reaction using tin tetrachloride to replace the zinc chloride catalytic, yield from 75% to a 88%; using five fluoro phenol instead of the nitro phenol to prepare phosphoric acid ester side chain, so that the phosphoric acid ester side chain of the yield from 80% up to 95%.
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Paragraph 0009
(2019/03/28)
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- Lenvatinib derivatives, preparation method and application
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The present invention relates to a compound shown in a general formula (I) and stereoisomers or pharmacologically acceptable salts thereof, as well as to application to preparation of drugs for resisting tumors. The structure of the compound of the genera
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Paragraph 0317; 0321-0327
(2020/01/03)
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- PROCESS FOR THE PREPARATION OF (Sp)-SOFOSBUVIR AND INTERMEDIATES THEREOF
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The present invention is directed towards process for preparation of an optically pure (Sp)-Sofosbuvir of Formula-(I) and its intermediate namely (Sp)-isomer of isopropyl alanyl phosphoramidate of Formula (III) thereof.
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Page/Page column 9; 10
(2018/03/28)
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- A process for preparing N - [(S)- (2, 3, 4, 5, 6 - Pentafluorophenyloxy) phenoxy phosphoryl] - L - alanine isopropyl ester method
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The invention discloses a method for preparation of N-[(S)-(2,3,4,5,6-pentafluorophenyloxy)phenoxy phosphoryl]-L-alanine isopropyl ester; the method comprises the steps: first of all, carrying out a reflux reaction of dichloro phenyl phosphate and pentafl
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Paragraph 0017; 0030-0037
(2018/10/11)
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- PHOSPHORAMIDATES FOR THE TREATMENT OF HEPATITIS B VIRUS
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Disclosed are compounds and compositions to the treatment of infectious diseases and methods of treating such diseases. The compounds and compositions include derivatives of clevudine. The compounds and compositions include derivatives of clevudine in com
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Page/Page column 68; 69
(2018/04/11)
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- Nucleotide phosphoramidate formulation
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Compound 1 with the formula I is an HCV antiviral protide, which is surprisingly soluble in ethanol, thereby facilitating the preparation of pharmaceutical formulations, such as adsorbed mesoporous carriers or SEDDS of Pouton Types III or IV.
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Paragraph 0209; 0210; 0213; 0214; 0215; 0216; 0217
(2017/12/27)
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- 2-dialkyl substituted nucleoside analogue and uses thereof
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The present invention discloses a 2-dialkyl substituted nucleoside analogue and uses thereof, wherein the 2-dialkyl substituted nucleoside analogue is the nucleoside represented by a general formula I, a nucleoside aminophosphate compound, or a pharmaceut
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Paragraph 0111; 0112; 0113; 0114; 0115
(2017/02/28)
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- A deuterium generation of sophie cloth wei and use thereof
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The invention discloses deuterated Sofosbuvir and application thereof. Deuterated Sofosbuvir is a nucleoside phosphoramidate compound shown in the formula I or II, or stereisomer, salt, hydrate, solvate or crystal of the nucleoside phosphoramidate compound. The compound and the composition are used for treating flaviviridae viruses, and particularly used for treating infection of hepatitis c virus (HCV); and the deuterated Sofosbuvir has good HCV resistance.
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Paragraph 0083; 0101-0103
(2017/11/23)
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- Method for preparing sofosbuvir intermediate
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The invention relates to the technical field of medicinal chemistry, and in particular to a method for preparing a sofosbuvir intermediate N-[(S)-(2,3,4,5,6-pentafluorophenyl) phenoxyl phosphoryl-L-alanine isopropyl ester. According to the method, a compo
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Paragraph 0042; 0043; 0051-0053; 0058-0061
(2017/03/25)
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- A rope non-cloth Wei preparation of intermediate
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The invention discloses a preparation method of a sofosbuvir intermediate, which comprises the following step: in an anhydrous non-protonic solvent, carrying out dynamic kinetic resolution on a compound disclosed as Formula (II) under the action of an organic alkali and/or inorganic alkali to prepare a compound disclosed as Formula (I), wherein the non-protonic solvent is one or more of ester solvent, ketone solvent and ether solvent, the organic alkali and/or inorganic alkali account/accounts for 0.1-10 wt% of the compound disclosed as Formula (II), the temperature of the dynamic kinetic resolution is 10-30 DEG C, and the time of the dynamic kinetic resolution is 5-10 hours. The preparation method has the advantages of high conversion rate, high product purity and low cost, and is environment-friendly.
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Paragraph 0025; 0047-0051
(2017/08/25)
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- DIOXOLANE ANALOGUES OF URIDINE FOR THE TREATMENT OF CANCER
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The invention provides compounds of formula (I), wherein: R1 is OR11, or NR5R5'; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(=O)R6, O(C=O)R6 or O(C=O)OR6; R5′ is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.
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Page/Page column 51
(2016/03/22)
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- PHOSPHORAMIDATES FOR THE TREATMENT OF HEPATITIS B VIRUS
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Disclosed are compounds to the treatment of infectious diseases and methods of treating such diseases. The compounds are derivatives of clevudine.
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Page/Page column 55
(2016/07/05)
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- NUCLEOSIDE PHOSPHORAMIDATES USEFUL FOR THE TREATMENT OF VIRAL INFECTIONS AND PREPARATION THEREOF
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The present invention relates to an industrially applicable process for the preparation of phosphoramidates useful for the treatment of viral infections, such as sofosbuvir, and to intermediates useful for the preparation thereof. Formula (I):
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Page/Page column 25; 26
(2016/10/11)
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- STABILIZED NUCLEOTIDES FOR MEDICAL TREATMENT
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5′-Deuterated nucleosides and nucleotides and modifications thereof are provided for use in medical therapies, including as antiviral, anti-tumor and anti-neoplastic agents. In one embodiment, compounds, methods and uses are provided for the treatment of
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Paragraph 0684-0685
(2016/02/12)
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- Beta-D-2'-DEOXY-2'-alpha-FLUORO-2'-beta-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT
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A compound of the structure: or a pharmaceutically acceptable salt or composition thereof for the treatment of a host infected with or exposed to an HCV virus or other disorders more fully described herein.
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- A PROCESS FOR THE PREPARATION OF SOFOSBUVIR INTERMEDIATES and ITS POLYMORPH
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The present invention provides a novel process for preparation N-[(2,3,4,5,6- Pentafluorophenoxy)phenoxyphosphinyl]-L-alanine 1-methylethyl ester (formula 2) and resolving the formula 2 in the presence base to form N-[(S)-(2,3,4,5,6- Pentafluorophenoxy)phenoxyphosphinyl]-L-alanine 1-methylethyl ester (formula 2').
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- 1',4'-THIO NUCLEOSIDES FOR THE TREATMENT OF HCV
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Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 1′,4′-thio nucleoside compounds which display remarkable efficacy and bioavailability for the treatment of, for example, HCV infection in a human. In certain embodiments, the compounds are of Formula 3001: or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form, or polymorphic form thereof; wherein Base, RA, RB, W, X, Y, and Z are as described herein.
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Paragraph 0318; 0319; 0320; 0321; 0322
(2015/01/06)
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- 2'-SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
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The present invention relates to 2'-Substituted Nucleoside Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, X, R1, R2 and R3 are as defined herein. The present invention also relates
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Page/Page column 74-75
(2012/11/06)
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- Synthesis of diastereomerically pure nucleotide phosphoramidates
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Prodrugs of therapeutic nucleoside monophosphates masked as phosphoramidate derivatives have become an increasingly important class of antiviral drugs in pharmaceutical research for delivering nucleotides in vitro and in vivo. Conventionally, phosphoramidate derivatives are prepared as a mixture of two diastereomers. We report a class of stable phosphoramidating reagents containing an amino acid ester and two phenolic groups, one unsubstituted and the other with electron-withdrawing substituents. The reagents can be isolated as single diastereomers and reacted with the 5′-hydroxyl group of nucleosides through selective nucleophilic displacement of the substituted phenol to prepare single diastereomer phosphoramidate products. This method has been used to prepare the HCV clinical candidate PSI-7977 in high yield and high diastereomeric purity.
- Ross, Bruce S.,Ganapati Reddy,Zhang, Hai-Ren,Rachakonda, Suguna,Sofia, Michael J.
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experimental part
p. 8311 - 8319
(2012/01/03)
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- N- [ (2 ' R) -2 ' -DEOXY-2 ' -FLUORO-2 ' -METHYL-P-PHENYL-5 ' -URIDYLYL] -L-ALANINE 1-METHYLETHYL ESTER AND PROCESS FOR ITS PRODUCTION
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Disclosed herein are nucleoside phosphoramidates of formula 4 and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals. Disclosed is also a process for preparing compound represented by formula 4: (Formula 4) wherein P* represents a chiral phosphorus atom, which comprises: a) reacting an isopropyl-alanate, (Formula A), a di-X'-phenylphosphate, (Formula B), 2'-deoxy-2f-fluoro-2'-C-methyluridine, (Formula 3), and a base to obtain a first mixture comprising 4; wherein X is a conjugate base of an acid, n is 0 or 1, and X' is a halogen, b) reacting the first mixture with a protecting compound to obtain a second mixture comprising 4; and c) optionally subjecting the second mixture to crystallization, chromatography or extraction in order to obtain 4.
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Page/Page column 52-53
(2010/12/18)
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