Infrared spectra and other properties predictions of 5-amino-3-methyl-4-isoxazolecarbohydrazide with electric field simulation using CPC model

Regiec, Andrzej; Wojciechowski, Piotr; Pietraszko, A.; Mączyński, Marcin

doi:10.1016/j.molstruc.2018.01.085

Cited by 11 publications

(11 citation statements)

References 39 publications

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“…The following reagents and substrates have been used in the synthesis of the considered compounds: starting materials, such as esters of 2-cyano-3-alkoxy-2-butenoate acids, which were used to synthesize known 5-amino-3-methyl-4-isoxazolecarboxylic acid [ 27 ], were prepared according to the highly efficient methods precisely described in [ 28 ]. 5-Amino-3-methylisoxazole-4-carbonyl chloride ( 1 , Scheme 1 ) was also prepared using the method described earlier [ 12 ]. Similarly to the method described by Freeman and Kim [ 29 ], 5-amino-2-(5-amino-3-methylisoxazol-4-yl)-oxazole-4-carbonitrile ( 2 ) was obtained in the reaction, which was conducted in 1-methyl-2-pyrrolidinone (NMP) at room temperature, between the commercially available aminomalononitrile tosylate (AMNT) and compound 1 .…”

Section: Resultsmentioning

confidence: 99%

“…The solution after filtration was evaporated in a vacuum and the residue was dilution with ethanol. The formed precipitate was filtered off and dried to give the compound 5c as a white solid (0.015 g, 12 Figure S7 in the Supplementary Material). Other spectral analyzes (IR, NMR) confirm that the product is identical to that obtained by Method A.…”

Section: Methods B (In Tetrachloromethane)mentioning

confidence: 99%

“…In our previous search for novel potent immunomodulatory, anti-inflammatory and anticancer agents, many of five-membered heterocycles with two heteroatoms, such as 5-amino-3-methyl-4-isoxazolecarboxylic acid [ 12 ], 5-amino-3-methyl-4-isothiazolecarboxylic acid [ 13 , 14 , 15 ] and 4-amino-1-methyl-5-imidazolecarboxylic acid derivatives [ 16 ] were designed and synthesized. The described results revealed that the isoxazole moiety was particularly responsible for the immunological activity of these compounds.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Biological Activity of New 7-Amino-oxazolo[5,4-d]Pyrimidine Derivatives

et al. 2020

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The synthesis of a series of novel 7-aminooxazolo[5,4-d]pyrimidines 5, transformations during their synthesis and their physicochemical characteristics have been described. Complete detailed spectral analysis of the intermediates 2–4, the N′-cyanooxazolylacetamidine by-products 7 and final compounds 5 has been carried out using MS, IR, 1D and 2D NMR spectroscopy. Theoretical research was carried out to explain the privileged formation of 7-aminooxazolo[5,4-d]pyrimidines in relation to the possibility of their isomer formation and the related thermodynamic aspects. Additionally, the single-crystal X-ray diffraction analysis for 5h was reported. Ten 7-aminooxazolo[5,4-d]pyrimidines 5 (SCM1–10) were biologically tested in vitro to preliminarily evaluate their immunological, antiviral and anticancer activity. Compounds SCM5 and SCM9 showed the best immunoregulatory profile. The compounds displayed low-toxicity and strongly inhibited phytohemagglutinin A-induced proliferation of human peripheral blood lymphocytes and lipopolysaccharide-induced proliferation of mouse splenocytes. Compound SCM9 caused also a moderate suppression of tumor necrosis factor α (TNF-α) production in a human whole blood culture. Of note, the compounds also inhibited the growth of selected tumor cell lines and inhibited replication of human herpes virus type-1 (HHV-1) virus in A-549 cell line. Molecular investigations showed that the compounds exerted differential changes in expression of signaling proteins in Jurkat and WEHI-231 cell lines. The activity of SCM5 is likely associated with elicitation of cell signaling pathways leading to cell apoptosis. The compounds may be of interest in terms of therapeutic utility as inhibitors of autoimmune disorders, virus replication and antitumor agents.

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Section: Resultsmentioning

confidence: 99%

Section: Methods B (In Tetrachloromethane)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis and Biological Activity of New 7-Amino-oxazolo[5,4-d]Pyrimidine Derivatives

et al. 2020

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“…Assuming the presence of a carbonyl group in the tested compound, it should be taken into account that stretching vibration bands (mostly strong or of very strong intensity) of carbonyl groups in the IR spectrum can be often covered or perturbed with intensive bands of deformation vibrations of N-H (mainly scissoring vibration of NH 2 ) groups. For example, 5-amino-3-methyl-4-isoxazolecarbohydrazide (without an N -methyl group), structurally similar to compound 4, exhibits the intense bending (scissoring) vibration of the NH 2 amino group with a maximum at about 1616 cm −1 and a weak scissoring vibration of the terminal NH 2 of the hydrazide group at about 1684 cm −1 [ 35 ]. Therefore, for this reason, the N -deuteratation of RM33 was carried out to remove potentially disturbing and covering bands to unambiguously assign the appropriate band to the carbonyl group (see Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Physicochemical Characteristics and Plausible Mechanism of Action of an Immunosuppressive Isoxazolo[5,4-e]-1,2,4-Triazepine Derivative (RM33)

et al. 2021

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Previous studies demonstrated strong anti-inflammatory properties of isoxazolo[5,4-e]-1,2,4-triazepine (RM33) in vivo. The aim of this investigation was to describe synthesis, determine physicochemical characteristics, evaluate biological activities in murine and human in vitro models, as well as to propose mechanism of action of the compound. The compound was devoid of cell toxicity up to 100 μg/mL against a reference A549 cell line. Likewise, RM33 did not induce apoptosis in these cells. The compound stimulated concanavalin A (ConA)-induced splenocyte proliferation but did not change the secondary humoral immune response in vitro to sheep erythrocytes. Nevertheless, a low suppressive effect was registered on lipopolysaccharide (LPS)-induced splenocyte proliferation and a stronger one on tumor necrosis factor alpha (TNFα) production by rat peritoneal cells. The analysis of signaling pathways elicited by RM33 in nonstimulated resident cells and cell lines revealed changes associated with cell activation. Most importantly, we demonstrated that RM33 enhanced production of cyclooxygenase 2 in LPS-stimulated splenocytes. Based on the previous and herein presented results, we conclude that RM33 is an efficient, nontoxic immune suppressor with prevailing anti-inflammatory action. Additionally, structural studies were carried out with the use of appropriate spectral techniques in order to unequivocally confirm the structure of the RM33 molecule. Unambiguous assignment of NMR chemical shifts of carbon atoms of RM33 was conducted thanks to full detailed analysis of 1H, 13C NMR spectra and their two-dimensional (2D) variants. Comparison between theoretically predicted chemical shifts and experimental ones was also carried out. Additionally, N-deuterated isotopologue of RM33 was synthesized to eliminate potentially disturbing frequencies (such as NH, NH2 deformation vibrations) in the carbonyl region of the IR (infrared) spectrum to confirm the presence of the carbonyl group.

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“…The following reagents and substrates were used in the synthesis of the considered compounds. Starting materials, such as esters of 2-cyano-3-alkoxy-2-butenoate acids and semi-products (i.e., known ethyl [ 32 ] or methyl [ 33 ] esters of 5-amino-3-methyl-4-isoxazolecarboxylic acid), were prepared according to the highly efficient, environmentally friendly methods precisely described in [ 34 , 35 ] and [patent priority number PL20110397559, PL 216764 B1 20140530, PL 216770 B1 20140530]. Known 5-amino-3-methyl-4-isoxazolecarboxylic acid (compound 1 , Scheme 1 ) was obtained by hydrolysis of its appropriate ethyl or methyl esters with a boiling water solution of sodium hydroxide.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative

et al. 2018

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This work describes the synthesis of a new series of isoxazole derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10) was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The isoxazole derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA)-induced proliferation of peripheral blood mononuclear cells (PBMCs) to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenyl)methylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3) compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF α) production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models.

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Infrared spectra and other properties predictions of 5-amino-3-methyl-4-isoxazolecarbohydrazide with electric field simulation using CPC model

Cited by 11 publications

References 39 publications

Synthesis and Biological Activity of New 7-Amino-oxazolo[5,4-d]Pyrimidine Derivatives

Synthesis and Biological Activity of New 7-Amino-oxazolo[5,4-d]Pyrimidine Derivatives

Synthesis, Physicochemical Characteristics and Plausible Mechanism of Action of an Immunosuppressive Isoxazolo[5,4-e]-1,2,4-Triazepine Derivative (RM33)

Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative

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