- Synthesis, protolytic equilibria, and antimicrobial action of nifuroxazide analogs
-
The present paper reports on the synthesis of four hydrazones derived from 5-nitro-2-furfural, 5-nitro-2-thiophenal, isoniazid, 2,4- and 3,4-dihydroxy-N′-methylenebenzohydrazide. The acid-base dissociation constants of these compounds were determined in an aqueous solution. The protolytic equilibria-related ability of hydrazones to “sense” anions in dimethyl sulfoxide-containing water of different concentrations is studied using spectrophotometry, NMR spectroscopy, and quantum chemistry methods. The antimicrobial action of the hydrazones was tested and compared with that of the known drug nifuroxazide.
- Gamov,Kiselev,Murekhina,Zavalishin,Aleksandriiskii,Kosterin, D.Yu.
-
-
- Pyrazole derivatives of medically relevant phenolic acids: Insight into antioxidative and anti-lox activity
-
Background: From the point of view of medicinal chemistry, compounds containing phenolic and pyrazolic moiety are significant since they are often constituents of bioactive compounds. Objective: The aims of this study were to synthesize pyrazole derivatives of medically relevant phenolic acids, confirm their structure, and evaluate their antioxidative and anti-LOX activities. Methods: Phenolic pyrazole derivatives were obtained, starting from esters of medically relevant phenolic acids. The structures of all obtained compounds were determined by NMR and IR spectroscopy, and UV-Vis spectrophotometry. In addition, the single-crystal X-ray diffraction was used. Pyrazole derivatives were tested for their in vitro antioxidative (DPPH assay), and lipoxygenase (LOX) inhibitory ac-tivities. Radical quenching mechanism was estimated using DFT and thermodynamic approach, while molecular docking was used to estimate the binding mode within the enzyme. Results: Pyrazole derivatives were obtained in high yields. The crystal structure of a new compound 3e was determined. Pyrazole derivative with catechol moiety 3d exhibited excellent radical scavenging ac-tivity, while compound 3b exhibited the best anti-LOX activity. Molecular docking study revealed that there is no direct interaction of any ligand with the active site of LOX-Ib, but pyrazoles 3a-e behave as inhibitors blocking the approach of linoleic acid to the active site. Conclusion: In this research, protocatechuic and vanillic acid pyrazole derivatives have been obtained for the first time. In vitro antioxidative assay suggests that pyrazole derivate of protocatechuic acid is a powerful radical scavenger, while anti-LOX assay indicates a pyrazole derivative with 4-hydroxyphenyl moiety.
- Bogdanovi?, Goran A.,Brankovi?, Jovica,Milovanovi?, Vesna,Mladenovi?, Milan,Novakovi?, Sla?ana,Petrovi?, Vladimir P.,Petrovi?, Zorica D.,Simijonovi?, Du?ica
-
p. 807 - 819
(2021/10/21)
-
- Aromatic acyl hydrazone derivative and application thereof as NA inhibitor
-
The invention relates to an aromatic acyl hydrazone derivative as shown in a structural formula I, pharmaceutically acceptable salt and a pharmaceutical composition thereof, and application of the aromatic acyl hydrazone derivative and the pharmaceutically acceptable salt and the pharmaceutical composition in preparation of an influenza virus neuraminidase inhibitor, wherein R is one of trifluoromethyl, nitryl, 3-methyl-4-nitryl, 3-hydroxyl-4-nitryl, 3-nitryl-4-hydroxyl, hydroxyl, dihydroxyl, dinitryl, 3-methoxy-4-hydroxyl or trihydroxyl; Y is selected from hydroxyl, dihydroxyl, 2-hydroxyl-3-methoxy, 2-hydroxyl-4-methoxy,2-hydroxyl-5-methoxy,2-hydroxyl-6-methoxy,3-hydroxyl-2-methoxy,3-hydroxyl-4-methoxy,3-hydroxyl-5-methoxy,3-hydroxyl-6-methoxy,4-hydroxyl-2-methoxy,4-hydroxyl-3-methoxy,4-hydroxyl-3,5-dimethoxy, trihydroxyl, 4-hydroxyl-3-ethoxy, or 4-hydroxyl-3,5-dimethoxy; w is selected from CH or N; and z is selected from CH or N.
- -
-
Paragraph 0039; 0044-0046; 0323-0327
(2020/12/30)
-
- Green synthesis of benzamide-dioxoisoindoline derivatives and assessment of their radical scavenging activity – Experimental and theoretical approach
-
A series of benzamide-dioxoisoindoline derivatives 3 was obtained, starting from phthalic anhydride and different benzoyl hydrazides 2, by ultrasound irradiation in water as solvent and without any catalyst. Five obtained compounds have been reported in this study for the first time and crystal structure of compound 3h was determined. All compounds were subjected to experimental determination of their antioxidative potential. DPPH test revealed that newly synthesized phenolic compounds 3d, 3e, and 3j are the best antioxidants. Additionally, probable radical scavenging pathway was analysed for reactions of the most active compounds and some radicals that can be found in living cells.
- Bogdanovi?, Goran A.,Milovanovi?, Vesna M.,Novakovi?, Sla?ana,Petrovi?, Vladimir P.,Petrovi?, Zorica D.,Simijonovi?, Du?ica
-
-
- Design, synthesis, and evaluation of simple phenol amides as ERRγ agonists
-
Herein we report the design and synthesis of a series of simple phenol amide ERRγ agonists based on a hydrazone lead molecule. Our structure activity relationship studies in this series revealed the phenol portion of the molecule to be required for activity. Attempts to replace the hydrazone with more suitable chemotypes led to a simple amide as a viable alternative. Differential hydrogen-deuterium exchange experiments were used to help understand the structural basis for binding to ERRγ and aid in the development of more potent ligands.
- Lin, Hua,Doebelin, Christelle,Patouret, Rémi,Garcia-Ordonez, Ruben D.,Ra Chang, Mi,Dharmarajan, Venkatasubramanian,Bayona, Claudia Ruiz,Cameron, Michael D.,Griffin, Patrick R.,Kamenecka, Theodore M.
-
p. 1313 - 1319
(2018/03/21)
-
- Oxadiazole compound and application thereof to preparation of medicament for preventing and/or treating type 2 diabetes
-
The invention relates to a total chemical synthesis method for novel oxadiazole PTP1B (protein tyrosine phosphatase 1B) and application of the novel oxadiazole PTP1B to a medicament for treating type 2 diabetes. The structural formula of the oxadiazole compound is shown in the description. The activity of PTP1B is inhibited, and the sensitivity of an insulin receptor is enhanced, so that the compound has good treatment effects on insulin resistance type 2 diabetes.
- -
-
Paragraph 0020; 0022
(2017/07/07)
-
- Development of hydroxy-based sphingosine kinase inhibitors and anti-inflammation in dextran sodium sulfate induced colitis in mice
-
Sphingosine kinase (SphK)-catalyzed production of sphingosine-1-phosphate (S1P) regulates cell growth, survival and proliferation as well as inflammatory status in animals. In recent study we reported the N′-(3-(benzyloxy)benzylidene)-3,4,5-trihydroxybenzohydrazide scaffold as a potent SphK inhibitor. As a continuation of these efforts, 51 derivatives were synthesized and evaluated by SphK1/2 inhibitory activities for structure-activity relationship (SAR) study. Among them, 33 was identified as the most potent SphK inhibitor. Potency of 33 was also observed to efficiently decrease SphK1/2 expression in human colorectal cancer cells (HCT116) and significantly inhibit dextran sodium sulfate (DSS)-induced colitis as well as the decreased expression of interleukin (IL)-6 and cyclooxygenase-2 (COX-2) in mouse models. Collectively, 33 was validated as an effective SphK inhibitor, which can be served as anti-inflammatory agent to probably treat inflammatory bowel diseases in human.
- Xi, Meiyang,Ge, Jun,Wang, Xiaojian,Sun, Chenbin,Liu, Tianqi,Fang, Liang,Xiao, Qiong,Yin, Dali
-
p. 3218 - 3230
(2016/07/06)
-
- Ultrasound-assisted, convenient and widely applicable 1,1′-carbonyl-diimidazole-mediated "One-pot" syntheses of acyl/sulfonyl hydrazines
-
Acyl / sulfonyl hydrazines were synthesized in a one-pot reaction from carboxylic acid/aryl sulfonic acid in the presence of 1,1′-carbonyl diimidazole (CDI) under ultrasound as well as under conventional heating. The reaction was performed on diverse organic molecules including simple benzoic acid (1), electron-donating and electron-withdrawing substituted benzoic acids, biologically active compounds like coumarin-3-carboxylic acid (12), 7-hydroxycoumarin-4-acetic acid (13), and therapeutic drugs like ibuprofen (14), flurbiprofen (15), naproxen (16) or tricyclic adamantane carboxylic acid (17). Benzene sulfonic acid (18) and its derivatives (19, 20, 21 and 22) were used to prepare corresponding sulfonyl hydrazide. All products were synthesized in very good yield via ultrasonic irradiation method and characterized by spectroscopic techniques including EIMS, 1H NMR, 13C NMR, IR. The method was found very simple, facile, efficient and high yielding (>90).
- Khan, Khalid Mohammed,Salar, Uzma,Fakhri, Muhammad Imran,Taha, Muhammad,Hameed, Abdul,Perveen, Shahnaz,Voelter, Wolfgang
-
p. 637 - 644
(2015/11/09)
-
- Synthesis and Structure-Activity relationships of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3' or C-7 catechol or related aromatics
-
A series of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3' catechol-containing (pyridinium-4-thio)methyl groups and 2-isocephems with C-7 catechol related aromatics have been prepared and evaluated for antimicrobial activity. It turns out that these compounds have highly potent activity against Gram-negative bacteria, especially resistant pathogens such as Pseudomonas aeruginosa. The most active compound of the series was (6S,7S)-7-[2-(2-aminothiazol-4-yl)-2-[(Z)-[(1,5-dihydroxy- 4-pyridon-2-yl)methoxy]imino]acetamido]-3-[[[(4-methyl-5- carboxymethyl)thiazol-2-yl]thio] methyl]-8-oxo-1-aza-4-thiabicyclo [4.2.0]-aza-4-thiabicyclo [4.2.0] oct-2-ene-2-carboxylic acid which exhibited potent in vitro activity against clinically isolated P. aeruginosa and Acinetobacter baumanii which is also resistant to many anti-infectives, and good in vivo efficacy against clinically isolated P aeruginosa.
- Tsuji, Koichi,Tsubouchi, Hidetsugu,Yasumura, Koichi,Matsumoto, Makoto,Ishikawa, Hiroshi
-
p. 2135 - 2149
(2007/10/03)
-
- Cephalosporin β-lactam compound and medicinal composition
-
There are disclosed a β-lactam compound represented by the formula (I): STR1 wherein R1 and R2 are independently a hydrogen atom or a lower alkyl group; M is a hydrogen atom, a protective group or an eliminatable group which is easily hydrolyzable in a human body; R' and R" are independently a hydrogen atom or a protective group; A is a mercapto group substituted by a substituted or unsubstituted polycyclic nitrogen-containing heterocyclic ring or a group represented by the following formula (a): where R3 and R4 are independently a hydrogen atom or a lower alkyl group, provided that R1 and R2 are both hydrogen atoms, both R3 and R4 being hydrogen atoms are excluded, or its pharmaceutically acceptable salt, and a method for preparing the same , medicinal composition for microbism therapy containing the same and intermediates for synthesis of the same.
- -
-
-
