- Synthesis method of 2-methyl-3-hydroxyquinoline and preparation method of quinotrione disperse dye
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The invention relates to a synthesis method of 2-methyl-3-hydroxyquinoline and a preparation method of a quinotrione disperse dye. The synthesis method of the 2-methyl- 3-hydroxyquinoline comprises the steps of mixing o-aminobenzaldehyde, chloroacetone, a base catalyst, a phase transfer catalyst and a solvent, adjusting the pH value to 11 to 13, and fully contacting the raw materials under the action of the phase transfer catalyst to obtain a uniformly mixed homogeneous mixed solution with a specific pH value; and then carrying out micro-channel reaction on the mixed solution. In the micro-channel reaction process, reaction materials in the mixed solution is subjected to micron or millimeter-level micro contact reaction, the reaction speed and the reaction selectivity are improved, and theprobability of self-condensation polymerization of o-aminobenzaldehyde or chloroacetone in the micro-channel reaction process is reduced; and therefore, the yield of the 2-methyl-3-hydroxyquinoline is improved.
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Paragraph 0089-0134
(2020/12/30)
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- (PYRIDIN-2-YL)AMINE DERIVATIVES AS TGF-BETA R1 (ALK5) INHIBITORS FOR THE TREATMENT OF CANCER
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The present invention relates to pharmaceutical compounds, compositions and methods, especially as they are related to compositions and methods for the treatment and/or prevention of a proliferation disorder associated with ΤGFβR1 activity, such as a cancer or fibrosis. The invention provides compounds of Formula (I) and Formula (II) as further described herein having an acidic moiety that enhances tissue specificity for targeted tissues and organs. The invention includes pharmaceutical compositions, pharmaceutical combinations, and methods of use of these compounds for treating conditions including cancer or fibrosis.
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- Multi-Functional Oxidase Activity of CYP102A1 (P450BM3) in the Oxidation of Quinolines and Tetrahydroquinolines
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Tetrahydroquinoline, quinoline, and dihydroquinolinone are common core motifs in drug molecules. Screening of a 48-variant library of the cytochrome P450 enzyme CYP102A1 (P450BM3), followed by targeted mutagenesis based on mutation-selectivity correlations from initial hits, has enabled the hydroxylation of substituted tetrahydroquinolines, quinolines, and 3,4-dihydro-2-quinolinones at most positions around the two rings in good to high yields at synthetically relevant scales (1.5 g L?1 day?1). Other oxidase activities, such as C?C bond desaturation, aromatization, and C?C bond formation, were also observed. The enzyme variants, with mutations at the key active site residues S72, A82, F87, I263, E267, A328, and A330, provide direct and sustainable routes to oxy-functionalized derivatives of these building block molecules for synthesis and drug discovery.
- Li, Yushu,Wong, Luet L.
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p. 9551 - 9555
(2019/08/06)
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- [2-(2-Nitrophenyl)oxiran-1-yl](aryl(methyl))ketones in the synthesis of 3-hydroxyquinolin-4(1H)-ones and 2-arylquinolines
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The applicability of [2-(2-nitrophenyl)oxiran-1-yl](aryl(methyl))ketones in the synthesis of 3-hydroxyquinolin-4-ones and 2-arylquinolines was studied.
- Mamedov,Mamedova,Khikmatova,Mahrous,Korshin,Syakaev,Fayzullin,Mironova,Latypov, Sh. K.,Sinyashin
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p. 1020 - 1024
(2019/06/17)
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- Simple synthesis of 3-hydroxyquinolines via Na2S2O4-mediated reductive cyclization of (2-(2-nitrophenyl)oxiran-1-yl)(aryl)methanones (o-nitrobenzalacetophenone oxides)
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An efficient sodium dithionite (Na2S2O4)-mediated method for construction of 3-hydroxyquinolines via in situ Meinwald rearrangement/intramolecular reductive cyclization of o-nitrobenzalacetophenone oxides has been developed. The practical approach is of excellent functional group compatibility with as high as 98% yield under mild reaction conditions. Moreover, further manipulation successfully furnished 4-bromo substituted derivatives which may provide a promising potential application in exploring biologically active analogs of 3-hydroxyquinolines.
- Mamedov, Vakhid A.,Mamedova, Vera L.,Syakaev, Victor V.,Korshin, Dmitry E.,Khikmatova, Gul'naz Z.,Mironova, Ekaterina V.,Bazanova, Olga B.,Rizvanov, Il'dar Kh.,Latypov, Shamil K.
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p. 5082 - 5090
(2017/07/28)
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- 3-hydroxyquinoline derivative of new synthetic method
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An aniline compound such as aniline, 2,3-difluoroaniline, or 3-fluoroaniline; and a halo-oxirane compound such as 2-chloro-2-(diethoxymethyl)-3-methyloxirane and the like are caused to react in the presence of a base such as sodium bicarbonate to obtain an N-substituted aniline compound such as 2-chloro-1,1-diethoxy-3-(phenylamino)butan-2-ol, 2-chloro-3-(2,3-difluoroamino)-1,1-diethoxybutan-2-ol, or 2-chloro-1,1-diethoxy-3-(3-fluorophenylamino)butan-2-ol; and then causing the N-substituted aniline compound to react in the presence of an acid such as hydrochloric acid to obtain a 3-hydroxyquinoline derivative such as 2-methylquinolin-3-ol, 7,8-difluoro-2-methylquinolin-3-ol, or 7-fluoro-2-methylquinolin-3-ol, 5-fluoro-2-methylquinolin-3-ol.
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- Synthesis of fluorine-containing phosphodiesterase 10A (PDE10A) inhibitors and the in vivo evaluation of F-18 labeled PDE10A PET tracers in rodent and nonhuman primate
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A series of fluorine-containing PDE10A inhibitors were designed and synthesized to improve the metabolic stability of [11C]MP-10. Twenty of the 22 new analogues had high potency and selectivity for PDE10A: 18a-j, 19d-j, 20a-b, and 21b had IC50 values 18F]18a-e, [18F]18g, and [18F]20a were radiosynthesized by 18F-introduction onto the quinoline rather than the pyrazole moiety of the MP-10 pharmacophore and performed in vivo evaluation. Biodistribution studies in rats showed ~2-fold higher activity in the PDE10A-enriched striatum than nontarget brain regions; this ratio increased from 5 to 30 min postinjection, particularly for [18F]18a-d and [18F]20a. MicroPET studies of [18F]18d and [18F]20a in nonhuman primates provided clear visualization of striatum with suitable equilibrium kinetics and favorable metabolic stability. These results suggest this strategy may identify a 18F-labeled PET tracer for quantifying the levels of PDE10A in patients with CNS disorders including Huntington's disease and schizophrenia.
- Li, Junfeng,Zhang, Xiang,Jin, Hongjun,Fan, Jinda,Flores, Hubert,Perlmutter, Joel S.,Tu, Zhude
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p. 8584 - 8600
(2015/11/25)
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