2148-56-3Relevant articles and documents
Synthetic method for Laquinimod intermediate 2-amino-6-chlorobenzoic acid
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Paragraph 0022; 0029; 0033-0034; 0038; 0042-0043; 0047-0052, (2019/10/01)
The invention discloses a synthetic method for a Laquinimod intermediate 2-amino-6-chlorobenzoic acid. The synthetic method is characterized in that the 2-amino-6-chlorobenzoic acid can be obtained through the reaction of 3-chloro-2-methylaniline under the action of a protective agent and an oxidizing agent; and a reaction process includes the following steps: 1) uniformly mixing the 3-chloro-2-methylaniline, the protective agent and a solvent S1, performing stirring reaction for 1-2 h under 40-50 DEG C, and obtaining a mixture I at the end; 2) uniformly mixing the oxidizing agent, water and asolvent S2, introducing a protection gas, controlling a reaction temperature to be 145-155 DEG C and reaction pressure to be 5-7 atmospheric pressure so that a mixture II can be obtained, dropping the mixture I into the mixture II, controlling dropping time to be 50-70 min, then controlling the temperature to be 160-175 DEG C and the reaction pressure to be 8-10 atmospheric pressure, performing continuous reaction for 6-8 h, and obtaining a mixture III after cooling; 3) adding hydrochloric acid and a solvent S3 into the mixture III, controlling the reaction temperature to be 75-90 DEG C and the reaction pressure to be normal pressure, performing reaction for 0.5-1 h, and obtaining a mixture IV after cooling; and 4) adding a solvent S4 into the mixture IV, performing standing and layering,and concentrating, steaming and removing the solvents to obtain a product after an organic phase is washed by water and dried by a drying agent. The method is low in raw material cost and high in yield.
HETEROARYL DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSTION FOR PREVENTING OR TREATING DISEASES ASSOCIATED WITH PI3 KINASES, CONTAINING SAME AS ACTIVE INGREDIENT
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Paragraph 0439-0441, (2018/04/26)
The present invention relates to a heteroaryl derivative or a pharmaceutically acceptable salt thereof, a preparation method therefor, and a pharmaceutical composition for preventing or treating diseases associated with PI3 kinases, containing the same as an active ingredient. The heteroaryl derivative according to the present invention has an excellent effect of selectively inhibiting PI3 kinases, thereby being useful in preventing or treating PI3 kinase diseases such as: cancers, autoimmune diseases, and respiratory diseases.
Dihydropteridin-one derivatives or pharmaceutically acceptable salts thereof, preparation method thereof and pharmaceutical composition for use in preventing or treating PI3 kinase related diseases
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Paragraph 0175-0178, (2017/09/12)
The present invention relates to dihydropteridin-one derivatives or pharmaceutically acceptable salts thereof, a preparation method thereof, and a pharmaceutical composition comprising the same as an effective component for preventing or treating PI3 kinase-related diseases. According to the present invention, the dihydropteridin-one derivatives have excellent selective inhibitory effects on PI3 kinase, and thus may be beneficially used in preventing or treating PI3 kinase-related diseases such as the following: cancers including blood cancer, ovarian cancer, cervical cancer, breast cancer, large intestine cancer, liver cancer, stomach cancer, pancreatic cancer, colon cancer, periotoneal cancer, skin cancer, bladder cancer, prostate cancer, lung cancer, osteosarcoma, fibrous tumor, and brain tumor; autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, hyperthyroidism, myasthenia gravis, Crohnandprime;s disease, ankylosing spondylitis, psoriasis, pernicious anemia, and Sjogrenandprime;s syndrome; and respiratory diseases including chronic obstructive pulmonary disease (COPD), rhinitis, asthma, chronic bronchitis, chronic pulmonary inflammatory diseases, silicosis, pulmonary sarcoidosis, pleuritis, alveolitis, vasculitis, emphysema, pneumonia, and bronchiectasis.COPYRIGHT KIPO 2017
Pharmaceutical intermediates of a kind of double-chlorine Xilin 2 - amino -6 - chlorobenzoic acid synthesis method (by machine translation)
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Paragraph 0023; 0024; 0025; 0026; 0027; 0047; 0048-0050, (2017/01/02)
Invention discloses a double-chlorine Xilin pharmaceutical intermediates 2?Amino?6?Chlorobenzoic acid synthesis method, the method of the 4?Hydroxy?3?Methoxylphenylboronic ethanol, potassium chloride, potassium sulfite in the mixed solution, under the condition of heating, 2?Chlorotrifluoromethylbenzene?6?Nitrobenzene reaction of formic acid and cerium chloride, separating solid temperature of the solution is then reduced, filtering, concentrating under reduced pressure, desiccant dehydration, washing, recrystallization, to obtain the crystal 2?Amino?6?Chlorobenzoic acid. The whole reaction time can be controlled within 10 hours, the reaction yield can reach 80% or more, at the same time, the invention provides a new synthetic route, reaction yield in order to further enhance the basis of the good. (by machine translation)
A High-Throughput Assay for Arylamine Halogenation Based on a Peroxidase-Mediated Quinone-Amine Coupling with Applications in the Screening of Enzymatic Halogenations
Hosford, Joseph,Shepherd, Sarah A.,Micklefield, Jason,Wong, Lu Shin
supporting information, p. 16759 - 16763 (2016/02/12)
Arylhalides are important building blocks in many fine chemicals, pharmaceuticals and agrochemicals, and there has been increasing interest in the development of more "green" halogenation methods based on enzyme catalysis. However, the screening and development of new enzymes for biohalogenation has been hampered by a lack of high-throughput screening methods. Described herein is the development of a colorimetric assay for detecting both chemical and enzymatic arylamine halogenation reactions in an aqueous environment. The assay is based on the unique UV/Vis spectrum created by the formation of an ortho-benzoquinone-amine adduct, which is produced by the peroxidase-catalysed benzoquinone generation, followed by Michael addition of either a halogenated or non-halogenated arylamine. This assay is sensitive, rapid and amenable to high-throughput screening platforms. We have also shown this assay to be easily coupled to a flavin-dependent halogenase, which currently lacks any convenient colorimetric assay, in a "one-pot" workflow.
Synthesis and antitumor evaluation of novel 5-substituted-4-hydroxy-8- nitroquinazolines as EGFR signaling-targeted inhibitors
Jin, Yi,Li, Hui-Yuan,Lin, Li-Ping,Tan, Jinzhi,Ding, Jian,Luo, Xiaomin,Long, Ya-Qiu
, p. 5613 - 5622 (2007/10/03)
The synthesis and biological activity of a series of novel 5-substituted-4-hydroxy-8-nitroquinazolines that may function as inhibitors of EGFR- and/or ErbB-2-related oncogenic signaling are described. These compounds were prepared by SNAr reaction of 5-chloro-4-hydroxy-8- nitroquinazoline with alkyl or aryl amines, or alkyl alcohol as nucleophiles. Although the enzyme assay showed a weak inhibition effect against both EGFR and ErbB-2 tyrosine kinases, the cell-based antitumor activity turned out promising. Compounds having 5-anilino substituent exhibit high potency with 5-(4-methoxy)anilino-4-hydroxy-8-nitroquinazoline (1h) being the best dual EGFR/ErbB-2 inhibitors, which effectively inhibited the growth of both EGFR (MDA-MB-468, IC50 50 = 13 μM) overexpressing human tumor cell lines in vitro. More interestingly, the variation of the substituent(s) at the 3- and/or 4-position of the 5-anilino portion was found to modulate the selectivity and potency dramatically. However, compounds having an alkylamino or alkyloxy group at the 5-position of 4-hydroxy-8-nitroquinazolines are essentially inactive. These results are consistent with molecular modeling observations. This study was the first attempt to identify new structural types of dual EGFR/ErbB-2-related signaling inhibitors by incorporation of the anilino group at the 5-position of 4-hydroxy-8-nitroquinazolines' core structure, providing promising new templates for further development of potent inhibitors targeting both EGFR and ErbB-2 tyrosine kinases.
