7146-15-8Relevant articles and documents
Convenient method for the synthesis of some novel chiral methyl 2-(2-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)propanoate derivatives and biological evaluation of their antioxidant, cytotoxic, and molecular docking properties
Matam, Sivakumar,Kaliyan, Prabakaran,Selvaraj, Loganathan,Muthu, Seenivasa Perumal,Lohanathan, Bharathi Priya,Viswanadhan, Vijaya Padma,Makala, Himesh,Venkatasubramanian, Ulaganathan
supporting information, p. 569 - 579 (2020/12/11)
Ten chiral methyl 2-(2-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)propanoate derivatives 6a-6j have been synthesized from optically pure amino methyl phenol 5 and 4-nitrophenyl chloroformate. These derivatives 6a-6j are characterized by 1H NMR, 13C NMR, FT-IR, and HRMS spectral techniques. Optical purity of these derivatives was confirmed by chiral HPLC method. Ten synthesized ester derivatives 6a-6j were screened for their in vitro antioxidant activity. Among the compounds 6b-d and 6h-j have exhibited comparable antioxidant activity with ascorbic acid as a standard. Compounds 6a and 6e-g have shown moderate antioxidant activity. Further, the in vitro cytotoxicity of these compounds were studied through MTT cell proliferation assay in addition the effect on LDH leakage and NO release. Among the derivatives, 6j showed extremely best activity and the IC50 value (12.54 ± 0.71 μM) is very close to doxorubicin (7.2 ± 0.58 μM) as a standard. Compounds 6b, 6h, and 6i showed better inhibition next to compound 6j on the viability of HepG2 cells with an IC50 value (μM) of 56.02 ± 1.4, 41.76 ± 0.58, and 38.17 ± 0.34, respectively. Also, molecular docking studies have been carried out with STAT-3 (PDB ID: 1BG1) and BCL-2 (PDB ID: 4AQ3) proteins against the four active compounds 6b, 6h, 6i, and 6j. The binding energies of the tested compounds were in the range of ?7.76 to ?8.41 kcal/mol, which is very close to doxorubicin (?8.53 kcal/mol) as a standard. These molecular docking results are in good agreement with the in vitro studies.
Preparation method of valsartan intermediate
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Paragraph 0027; 0029; 0031; 0034; 0036; 0039; 0041, (2020/07/21)
The invention belongs to the technical field of preparation of medical intermediates, and particularly relates to a preparation method of a valsartan intermediate. The method comprises the following steps: using L-valine and thionyl chloride as raw materials, in the presence of an organic solvent, carrying out esterification reaction to obtain L-valine methyl ester hydrochloride, then reacting theL-valine methyl ester hydrochloride, with 4-Bromomethyl-2-cyanobiphenyl under an alkaline condition, carrying out organic solvent extracting, crystallization, centrifugation and drying to obtain a crude product of N-[(2 '-cyano-1, 1'-biphenyl-4-yl) methyl]-L-valine methyl ester hydrochloride, and refining to obtain the product with main content of 99.5% or above and individual impurity content of0.1% or below. The method is mild in reaction condition, short in reaction time, simple and convenient to operate, simple in aftertreatment, high in yield, few in obtained product impurity, small inenvironmental pollution, low in cost and easy for industrial production.
Rhodium-Catalyzed Enantioselective Synthesis of Oxazinones via an Asymmetric Ring Opening-Lactonization Cascade of Oxabicyclic Alkenes
Yen, Andy,Pham, Anh Hoang,Larin, Egor M.,Lautens, Mark
supporting information, p. 7549 - 7553 (2019/10/02)
The rhodium-catalyzed asymmetric ring opening reaction of oxabicyclic alkenes is shown to be an efficient method for synthesizing chiral heterocycles. We demonstrate that the pairwise combination of chiral catalyst with chiral amino-acid-derived pronucleophiles results in a stereodivergent synthesis of diastereomeric hydroxyesters. A favorable conformational preference induces the subsequent lactonization of one diastereomer leading to the highly enantioselective synthesis of oxazinones.