160775-14-4Relevant articles and documents
Preparation method of baloxvir intermediate
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Paragraph 0066-0074, (2021/05/29)
The invention relates to a preparation method of a baloxvir intermediate, and belongs to the field of medicinal chemistry. The invention provides a preparation method of a baloxvir intermediate compound shown as a formula E and a baloxvir intermediate compound shown as a formula D. The preparation method of the compound shown as the formula E comprises the following steps: taking a compound of a formula A as a solvent, taking alkali as an acid-binding agent, reacting a compound of a formula B with carbon monoxide and the compound of the formula A under a pressurization condition under the action of a palladium-containing catalyst, and performing post-treatment to obtain the compound of the formula E. The preparation method of the compound shown as the formula D comprises the following steps: in the presence of a catalyst, in a mixed solvent containing water and an organic solvent mutually soluble with water, carrying out hydrolysis reaction on the compound shown as the formula E, and carrying out post-treatment to obtain the compound shown as the formula D. The preparation method of the baloxvir intermediate has the advantages of being safe, mild in reaction condition, easy to operate and the like.
SUBSTITUTED 3,4,12,12A-TETRAHYDRO-1H-[1,4]OXAZINO[3,4-C]PYRIDO[2,1-F][1,2,4]TRIAZINE-6,8-DIONE, PHARMACEUTICAL COMPOSITION, AND METHODS FOR PREPARING AND USING SAME
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Paragraph 0050; 0081, (2021/01/21)
Influenza is an acute infectious respiratory disease caused by the influenza virus. It is part of the group of Acute Respiratory Viral Infections (ARVI). It occasionally spreads in the form of epidemics and pandemics. Currently, more than 2000 variants of the influenza virus differing in the antigen spectrum have been identified. Given that influenza is a serious threat to public health (worldwide, these annual epidemics lead to 3-5 million cases of severe illness, millions of hospitalizations, and up to 650,000 deaths), it seems appropriate to search for new anti-influenza drugs with improved characteristics. The inventors surprisingly found out that the previously unknown substituted 3,4,12,12a-tetrahydro-1 H-[1,4] oxazino[3,4-c]pyrido[2,1-f] [1,2,4]triazine-6,8-dione of general formula 1, its stereoisomer, their prodrug, pharmaceutically acceptable salt, solvate, hydrate, and a crystalline or polycrystalline form thereof are effective agents for prophylaxis and treatment of viral diseases, including influenza where R1 is (6,7-difluoro-5,10-dihydrothieno[3,2-c][2]benzothiepin-10-yl, (7,8-difluoro-4,9-dihydrothieno[2,23-c][2]benzothiepin-4-yl, (3,4-difluorophenyl)(phenyl)methyl, (3,4-difluorophenyl)(2-methylsulfanylphenyl)methyl, diphenylmethyl, bis(4-fluorophenyl)-methyl; R2 is hydrogen or a protective group selected from a series comprising (C1-C3 alkyl) oxycarbonyloxy, {[(C1-C3 alkyl)oxycarbonyl]-oxy}methoxy, {[2-(C1-C3 alkyl) oxyethoxy]carbonyl}oxy, ({[(1R)-2-[(C1-C3alkyl)oxy]-1-methylethoxy}carbonyl)oxy, {[(3S)-ethoxyfuran-3-yloxy]-carbonyl}oxy, [(ethoxy-2H-pyran-4-yloxy)carbonyl]oxy,{[(1-acetylazetidine)-3-yloxy]carbonyl}oxy, {[(C1-C3alkyl) oxycarbonyl] -oxy}methoxy, ({[2-(C1-C3 alkyl)oxyethoxy]carbonyl}oxy) methoxy.
Development of a Quality Controllable and Scalable Process for the Preparation of 7,8-Difluoro-6,11-dihydrodibenzo[ b, e]thiepin-11-ol: A Key Intermediate for Baloxavir Marboxil
Zhou, Zihong,Wang, Zhongqing,Kou, Jingping,Wu, Shuming,Zhang, Junrong,Yuan, Xi,Wu, Xiwei,Li, Chuan-Hua,Liao, Gaohong
, p. 2716 - 2723 (2019/12/24)
A novel six-step synthesis of 7,8-difluoro-6,11-dihydrodibenzo[b,e]thiepin-11-ol (1) is described. Starting with 3,4-difloro-2-methylbenzoic acid and using diphenyl disulfide as an ideal sulfur source effectively solve the problems such as harsh reaction conditions, usage of smelly thiophenol, which might restrict the known process from pilot plant application. Large-scale applicability of this new route has been successfully demonstrated on kilogram-scale production to afford 1 with 98.04% purity in 75% overall yield. Meanwhile, the corresponding impurity profile was thus studied in detail and well documented.
C26-LINKED RAPAMYCIN ANALOGS AS MTOR INHIBITORS
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Paragraph 00465, (2019/11/21)
The present disclosure relates to mTOR inhibitors. Specifically, the embodiments are directed to compounds and compositions inhibiting mTOR, methods of treating diseases mediated by mTOR, and methods of synthesizing these compounds.
C40-, C28-, AND C-32-LINKED RAPAMYCIN ANALOGS AS MTOR INHIBITORS
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Paragraph 00530, (2019/11/19)
The present disclosure relates to mTOR inhibitors. Specifically, the embodiments are directed to compounds and compositions inhibiting mTOR, methods of treating diseases mediated by mTOR, and methods of synthesizing these compounds.
RAPAMYCIN ANALOGS AS MTOR INHIBITORS
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Paragraph 00361, (2018/12/03)
The present disclosure relates to rapamycin analogs of the general Formula (I). The compounds are inhibitors of mTOR and thus useful for the treatment of cancer, immune-mediated diseases and age related conditions.
