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.
A Novel N-Substituted Valine Derivative with Unique Peroxisome Proliferator-Activated Receptor γbinding Properties and Biological Activities
Peiretti, Franck,Montanari, Roberta,Capelli, Davide,Bonardo, Bernadette,Colson, Cécilia,Amri, Ez-Zoubir,Grimaldi, Marina,Balaguer, Patrick,Ito, Keiichi,Roeder, Robert G.,Pochetti, Giorgio,Brunel, Jean Michel
, p. 13124 - 13139 (2020/12/02)
A proprietary library of novel N-Aryl-substituted amino acid derivatives bearing a hydroxamate head group allowed the identification of compound 3a that possesses weak proadipogenic and peroxisome proliferator-Activated receptor γ(PPARI) activating properties. The systematic optimization of 3a, in order to improve its PPARγagonist activity, led to the synthesis of compound 7j (N-Aryl-substituted valine derivative) that possesses dual PPARI/PPARα agonistic activity. Structural and kinetic analyses reveal that 7j occupies the typical ligand binding domain of the PPARγagonists with, however, a unique high-Affinity binding mode. Furthermore, 7j is highly effective in preventing cyclin-dependent kinase 5-mediated phosphorylation of PPARγserine 273. Although less proadipogenic than rosiglitazone, 7j significantly increases adipocyte insulin-stimulated glucose uptake and efficiently promotes white-To-brown adipocyte conversion. In addition, 7j prevents oleic acid-induced lipid accumulation in hepatoma cells. The unique biochemical properties and biological activities of compound 7j suggest that it would be a promising candidate for the development of compounds to reduce insulin resistance, obesity, and nonalcoholic fatty liver disease.
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.
Cocrystallization of Chiral N7,N16-bis (S-1-Phenylethyl)-1,4,10,13-Tetraoxo-7,16-Diazacyclooctadecane-7,16-Dicarboxamide with Hydrochlorides of Methyl Ethers of Leucine and Valine Enantiomers
Fonari,Pluzhnik-Gladyr,Kamalov,Kravtsov, V. Kh.
, p. 143 - 150 (2019/04/30)
An attempt to co-crystallize N7,N16-bis(S-1-phenylethyl)-1,4,10,13-tetraoxo-7,16-diazacyclooctadecane-7,16-dicarboxamide (1) with hydrochlorides of methyl ethers (HCMEs) of L- and D-valine and also L- and D-leucine results in separate crystallization of diazacrown-ether 1 (or its monohydrate 1·H2O) and HCMEs of respective α-amino acids. Crystal structures of D-leucine 1·H2O (1) and HCME (2) compounds, which were not described previously, are solved by single crystal X-ray diffraction.
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.
Synthesis and antiviral activity of novel glycyrrhizic acid conjugates with D-amino acid esters
Fayrushina,Baltina,Baltina,Konovalova,Petrova,Eropkin, M. Yu.
, p. 456 - 462 (2017/08/08)
Glycyrrhizic acid (GA) conjugates with methyl and ethyl esters of D-amino acids (D-Trp, D-Phe, D-Tyr, D-Val, D-Leu) have been synthesized by the activated esters method using mixtures of N-hydroxybenzotriazole or N-hydroxysuccinimide with N,N′-dicyclohexylcarbodiimide. GA conjugate with D-Trp ethyl ester exhibited antiviral activity against influenza viruses A/H3N2, A/H1N1/pdm09, A/H5N1, B (SI > 10–29), and HRSV (SI > 25). GA conjugate with D-Trp methyl ester inhibited influenza virus A/H1N1/pdm09 (SI > 30).
Chemical differentiation of three DMSP lyases from the marine: Roseobacter group
Burkhardt, Immo,Lauterbach, Lukas,Brock, Nelson L.,Dickschat, Jeroen S.
supporting information, p. 4432 - 4439 (2017/07/10)
Dimethylsulfoniopropionate (DMSP) catabolism of marine bacteria plays an important role in marine and global ecology. The genome of Ruegeria pomeroyi DSS-3, a model organism from the Roseobacter group, harbours no less than three genes for different DMSP lyases (DddW, DddP and DddQ) that catalyse the degradation of DMSP to dimethyl sulfide (DMS) and acrylate. Despite their apparent similar function these enzymes show no significant overall sequence identity. In this work DddQ and DddW from R. pomeroyi and the DddP homolog from Phaeobacter inhibens DSM 17395 were functionally characterised and their substrate scope was tested using several synthetic DMSP analogues. Comparative kinetic assays revealed differences in the conversion of DMSP and its analogues in terms of selectivity and overall velocity, giving additional insights into the molecular mechanisms of DMSP lyases and into their putatively different biological functions.
Synthesis, in vitro antimicrobial, antioxidant, and antidiabetic activities of thiazolidine–quinoxaline derivatives with amino acid side chains
Shintre, Suhas A.,Ramjugernath, Deresh,Islam, Md Shahidul,Mopuri, Ramgopal,Mocktar, Chunderika,Koorbanally, Neil A.
, p. 2141 - 2151 (2017/08/03)
Abstract: A novel protocol for the rapid assembly of a hybrid framework based on amino acid, thiazolidine and quinoxaline scaffolds has been demonstrated by microwave irradiation. The quinoxalines with amino acid side chains 5a–5c were prepared in three steps from 2,4-dinitrofluorobenzene and the amino acids, valine, methionine, and tyrosine and subsequently reacted with four different aldehydes and thioglycolic acid to produce thiazolidine–quinoxaline hybrids with amino acid side chains 6a–6l. All synthesized compounds were evaluated for their in vitro antimicrobial, antioxidant, and antidiabetic activities. Compounds 6f, 6j, and 6k showed broad spectrum antimicrobial activity against Gram +ve and Gram –ve bacteria, whilst 6h, 6k, and 6l showed the best antioxidant activity in the same order of magnitude to that of ascorbic acid. Four of the compounds, 5c, 6d, 6g, and 6k showed activity against α-glucosidase and α-amylase similar to acarbose. Those compounds showing antibacterial activity possessed 4-fluorophenyl and 4-methoxyphenyl groups along with methionine and tyrosine side chains while the compounds showing antioxidant, α-glucosidase, and α-amylase activity contained 4-nitrophenyl and 4-methoxyphenyl groups on the thiazolidine moiety with mainly methionine and tyrosine side chains. The α-glucosidase and α-amylase inhibitory compound 5c did not have a thiazolidine moiety and 6d was the only active compound with a valine amino acid side chain. Compound 6k with a tyrosine side chain and a 4-methoxyphenylthiazolidine moiety on the quinoxaline scaffold showed good bioactivity in all three assays.
Ferrocene-modified amino acids: synthesis and in vivo bioeffects on hippocampus
Rodionov,Snegur,Simenel,Dobryakova, Yu. V.,Markevich
, p. 136 - 142 (2017/07/05)
A method for the ferrocene modification of amino acids of natural and synthetic origin has been developed. In the in vivo studies, the hippocampal electrical activity under the action of ferrocenyl(phenylpyrazolyl)glycine (1) was assessed. A meaningful rise (up to 25% compared to the control) in the response amplitudes of the focal potentials of the hippocampal region СА1 after intraperitoneal administration of compound 1 at the dose of 2.0 mg kg–1 was established.
Mechanochemical Encapsulation of Fullerenes in Peptidic Containers Prepared by Dynamic Chiral Self-Sorting and Self-Assembly
Szymański, Marek,Wierzbicki, Micha?,Gilski, Miros?aw,J?drzejewska, Hanna,Sztylko, Marcin,Cmoch, Piotr,Shkurenko, Aleksander,Jaskólski, Mariusz,Szumna, Agnieszka
supporting information, p. 3148 - 3155 (2016/03/23)
Molecular capsules composed of amino acid or peptide derivatives connected to resorcin[4]arene scaffolds through acylhydrazone linkers have been synthesized using dynamic covalent chemistry (DCC) and hydrogen-bond-based self-assembly. The dynamic character of the linkers and the preference of the peptides towards self-assembly into β-barrel-type motifs lead to the spontaneous amplification of formation of homochiral capsules from mixtures of different substrates. The capsules have cavities of around 800 ?3 and exhibit good kinetic stability. Although they retain their dynamic character, which allows processes such as chiral self-sorting and chiral self-assembly to operate with high fidelity, guest complexation is hindered in solution. However, the quantitative complexation of even very large guests, such as fullerene C60 or C70, is possible through the utilization of reversible covalent bonds or the application of mechanochemical methods. The NMR spectra show the influence of the chiral environment on the symmetry of the fullerene molecules, which results in the differentiation of diastereotopic carbon atoms for C70, and the X-ray structures provide unique information on the modes of peptide-fullerene interactions.
