- Production preparation method of p-nitrophenylethylamine hydrochloride
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The invention provides a production preparation method of p-nitrophenylethylamine hydrochloride, belongs to the technical field of drug synthesis, and solves the problems that in the prior art the synthetic p-nitrophenylethylamine hydrochloride is low in conversion rate of and is not suitable for large-scale industrial production. Synthesis steps include 1) amino protection, to be more specific, using beta-phenylethylamine as a raw material for reacting with an acyl protecting agent in a solvent to obtain an intermediate 1; 2) nitrating reaction, to be more specific, adding dropwise the intermediate 1 prepared by the step 1) into concentrated sulfuric acid, maintaining reaction temperature at room temperature, slowly adding dropwise concentrated nitric acid, after the completion of the reaction, adding crushed ice, adding an alkaline solution to adjust the pH to alkaline, and filtering to obtain an intermediate 2; and 3) deprotection, to be more specific, adding dropwise hydrochloric acid into the intermediate 2 in a solvent to adjust the pH to acid, heating to reflux, cooling, and precipitating the product p-nitrophenylethylamine hydrochloride. The production preparation method ofthe p-nitrophenylethylamine hydrochloride has low cost and high product yield, and is suitable for large-scale industrial production.
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Paragraph 0062
(2018/03/23)
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- PYRAZOLOPYRIMIDINE DERIVATIVES, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION FOR USE IN PREVENTING OR TREATING CANCER, AUTOIMMUNE DISEASE AND BRAIN DISEASE CONTAINING THE SAME AS AN ACTIVE INGREDIENT
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The present invention relates to a pyrazolopyrimidine derivative, a preparation method thereof and a pharmaceutical composition comprising the same as an active ingredient for the prevention or treatment of cancer, autoimmune disease and brain disease. The pyrazolopyrimidine derivative of the present invention exhibits excellent Bruton's tyrosine kinase inhibition activity, so that it can be effectively used as a pharmaceutical composition for the prevention or treatment of cancer, autoimmune disease and Parkinson's disease.
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Paragraph 242-246
(2018/12/02)
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- New p-methylsulfonamido phenylethylamine analogues as class III antiarrhythmic agents: Design, synthesis, biological assay, and 3D-QSAR analysis
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Class III antiarrhythmic agents selectively delay the effective refractory period (ERP) and increase the transmembrance action potential duration (APD). Using dofetilide (2) as a template of class III antiarrhythmic agents, we designed and synthesized 16 methylsulfonamido phenylethylamine analogues (4a-d and 5a-1). Pharmacological assay indicated that all of these compounds showed activity for increasing the ERP in isolated animal atrium; among them, the effective concentration of compound 4a is 1.6 × 10-8 mol/L in increasing ERP by 10 ms, slightly less potent than that of 2, 1.1 × 10-8 mol/L. Compound 4a also produced a slightly lower change in ERP at 10-5 M, ΔERP% = 17.5% (ΔERP% = 24.0% for dofetilide). On the basis of this bioassay result, these 16 compounds together with dofetilide were investigated by the three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques of comparative molecular field analysis (CoMFA), comparative molecular similarity index analysis (CoMSIA), and the hologram QSAR (HQSAR). The 3D-QSAR models were tested with another 11 compounds (4e-h and 5m-s) that we synthesized later. Results revealed that the CoMFA, CoMSIA, and HQSAR predicted activities for the 11 newly synthesized compounds that have a good correlation with their experimental value, r2 = 0.943, 0.891, and 0.809 for the three QSAR models, respectively. This indicates that the 3D-QSAR models proved a good predictive ability and could describe the steric, electrostatic, and hydrophobic requirements for recognition forces of the receptor site. On the basis of these results, we designed and synthesized another eight new analogues of methanesulfonamido phenylethyamine (6a-h) according to the clues provided by the 3D-QSAR analyses. Pharmacological assay indicated that the effective concentrations of delaying the ERP by 10 ms of these newly designed compounds correlated well with the 3D-QSAR predicted values. It is remarkable that the percent change of delaying ERP at 10-5 M compound 6c is much higher than that of dofetilide; the effective concentration of compound 6c is 5.0 × 10-8mol/L in increasing the ERP by 10 ms, which is slightly lower than that of 2. The results showed that the 3D-QSAR models are reliable and can be extended to design new antiarrhythmic agents.
- Liu, Hong,Ji, Ming,Luo, Xiaomin,Shen, Jianhua,Huang, Xiaoqin,Hua, Weiyi,Jiang, Hualiang,Chen, Kaixian
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p. 2953 - 2969
(2007/10/03)
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- A Modified Bischler-Napieralski Procedure for the Synthesis of 3-Aryl-3,4-dihydroisoquinolines
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A modification of the Bischler-Napieralski reaction for the cyclization of (1,2-diphenylethyl)amides to the 3-aryl-3,4-dihydroisoquinolines is presented.Elimination of the amide group as the nitrile via the retro-Ritter reaction is avoided by its conversion to an N-acyliminium intermediate with oxalyl chloride-FeCl3.Removal of the oxalyl group in refluxing MeOH-sulfuric acid provides the 3,4-dihydroisoquinolines in moderate to high yields.The method is also highly effective with (2-phenylethyl)amides.
- Larsen, Robert D.,Reamer, Robert A.,Corley, Edward G.,Davis, Paul,Grabowski, Edward J. J.,et al.
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p. 6034 - 6038
(2007/10/02)
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