- Nucleoside analogue and deuterated substance thereof as well as preparation method and application thereof
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The invention provides a nucleoside analogue and a deuterated substance thereof as well as a preparation method and an application of the deuterated substance, and belongs to the field of medicinal chemistry. The nucleoside analogue and the deuterated substance thereof are a compound shown as a formula I, or salt thereof, or a stereoisomer thereof, or a prodrug thereof, or a solvate thereof; wherein R1 to R34 are each independently selected from hydrogen or deuterium. The compound disclosed by the invention has a good inhibition effect on hepatitis C virus, MERS virus, SARS virus and novel coronavirus (SARS-CoV-2); moreover, the compound is long in elimination half-life period, capable of reducing the administration frequency of the medicine and improving the use safety, better in pharmacokinetics and good in druggability. Therefore, the compound provided by the invention can be used for preparing medicines for treating related virus infection, and has a good application prospect.
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Paragraph 0073-0077
(2021/04/17)
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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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Paragraph 00386
(2020/12/29)
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- 2,4,7-SUBSTITUTED-7-DEAZA-2'-DEOXY-2'-FLUOROARABINOSYL NUCLEOSIDE AND NUCLEOTIDE PRO-DRUGS AND USES THEREOF
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The present disclosure is concerned with 2,4,7-substituted-7-deaza-2'-deoxy-2'- fluoroarabinosyl nucleoside and nucleotide prodrugs that are capable of inhibiting viral infections and methods of treating viral infections such as, for example, human immunodeficiency virus (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), human cytomegalovirus (HCMV), chicken pox, infectious mononucleosis, mumps, measles, rubella, shingles, ebola, viral gastroenteritis, viral hepatitis, viral meningitis, human metapneumovirus, human parainfluenza virus type 1, parainfluenza virus type 2, parainfluenza virus type 3, respiratory syncytial virus, viral pneumonia, Chikungunya virus (CHIKV), Venezuelan equine encephalitis (VEEV), dengue (DENV), influenza, West Nile virus (WNV), zika (ZIKV), 229E, NL63, OC43, HKU1, Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus disease 2019 (SARS-CoV-2), using these compounds. 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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Paragraph 00348
(2020/12/30)
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- Catalytic Asymmetric Synthesis of the anti-COVID-19 Drug Remdesivir
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The catalytic asymmetric synthesis of the anti-COVID-19 drug Remdesivir has been realized by the coupling of the P-racemic phosphoryl chloride with protected nucleoside GS441524. The chiral bicyclic imidazole catalyst used is crucial for the dynamic kinetic asymmetric transformation (DyKAT) to proceed smoothly with high reactivity and excellent stereoselectivity (96 % conv., 22:1 SP:RP). Mechanistic studies showed that this DyKAT is a first-order visual kinetic reaction dependent on the catalyst concentration. The unique chiral bicyclic imidazole skeleton and carbamate substituent of the catalyst are both required for the racemization process, involving the phosphoryl chloride, and subsequent stereodiscriminating step. A 10 gram scale reaction was also conducted with comparably excellent results, showing its potential for industrial application.
- Chen, Jianzhong,Huo, Xiaohong,Li, Panpan,Wang, Mo,Wu, Zhengxing,Yuan, Qianjia,Zhang, Lu,Zhang, Wanbin,Zhang, Zhenfeng,Zou, Yashi
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supporting information
p. 20814 - 20819
(2020/10/15)
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- 4'-THIO-NUCLEOTIDE AND -NUCLEOSIDE PRODRUGS FOR THE TREATMENT OF CANCER
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The present disclosure is concerned with 4'-thio 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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Paragraph 00423
(2019/11/12)
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- Cyclic phosphoramidates as prodrugs of 2′-C-methylcytidine
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The currently approved treatment for hepatitis C virus infections is a combination of Ribavirin and pegylated Interferon. It leads to a sustained virologic response in approximately only half of the patients treated. For this reason there is an urgent need of new therapeutic agents. 2′-C-Methylcytidine is the first nucleoside inhibitor of the HCV NS5B polymerase that was efficacious in reducing the viral load in patients infected with HCV. The application of a monophosphate prodrug approach based on unprecedented cyclic phosphoramidates is reported. Our SAR studies led to compounds that are efficiently converted to the active triphosphate in human hepatocytes.
- Meppen, Malte,Pacini, Barbara,Bazzo, Renzo,Koch, Uwe,Leone, Joseph F.,Koeplinger, Kenneth A.,Rowley, Michael,Altamura, Sergio,Di Marco, Annalise,Fiore, Fabrizio,Giuliano, Claudio,Gonzalez-Paz, Odalys,Laufer, Ralph,Pucci, Vincenzo,Narjes, Frank,Gardelli, Cristina
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scheme or table
p. 3765 - 3770
(2009/12/24)
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