Synthesis, configuration and properties of some new 3,4,5-substituted oxazolidin-2-ones

Abstract

KEYWORDSNovel 3,4,5-substituted-oxazolidin-2-ones containing piperazine, 1-(4-chlorophenyl) piperazine, benzhydrylpiperazine, morpholine and piperidine rings were synthesized via Mannich reaction. The stereochemistry of syn and anti-isomers was assigned using the observed differences in the chemical shifts of the oxazolidinone ring protons and the values of vicinal coupling constants ( 3 J) between the two protons of the oxazolidin-2-one ring. For all compounds NOE (Nuclear Overhauser Effect) NMR spectra were measured in order to prove additionally the position of the substituents in the oxazolidin-2-one ring. Some physic chemical, steric and electronic properties of the compounds were determined in order to establish the similarity between the synthesized and reference compounds. The performed computations showed that the anti-isomers possessed lower electronic energies in comparison to these of syn-compounds. The nucleus-nucleus repulse energies (NRE) and the highest occupied molecular orbital energies (HOMO) of the anti-isomers are higher than the HOMO and NRE energies of syn-compounds. The Connolly Solvent Accessible Surface Area (SAS) and Connolly Molecular Surface Area (MS) values of anti-isomers are lower than these of syn-isomers. The same relations were observed for the reference compounds. Probably the differences in the electronic and steric properties are responsible not only for the higher LD50 value of the reference anti-compound, but also may contribute to the higher toxicity of the prepared anti-Mannich bases in comparison to that of the syn-diastereoisomers.

Synthesis of Some New Fused and Binary 1,3,4-Thiadiazoles as Potential Antitumor and Antioxidant Agents

“…Yellow crystals; yield, 80%; mp: 210 C, (E)-5-(4-Methoxybenzylidene)-2-(4-methoxyphenyl)-3-(1,3,4thiadiazol-2-yl)thiazolidin-4-one (19). A mixture of 1 (0.5 g, 5 mmol), 4-methoxybenzaldehyde (0.68 g, 5 mmol), and thioglycolic acid (0.46 g, 5 mmol) in toluene (15 mL (20). A mixture of 1 (0.5 g, 5 mmol) and isatine (0.7 g, 5 mmol) in a mixture of ethanol/glacial acetic acid (10 mL, 9:1) was heated under reflux for 2 h, then thiosemicarbazide (0.45 g, 5 mmol) was added.…”

“…The antitumor properties of 1,2,4-triazole and 1,3,4-thiadiazole derivatives [20] prompted us to synthesize thiadiazole derivative incorporated with triazole moiety to enhance its antitumor activity. Thus, multicomponent reaction of 1 with isatin and thiosemicarbazide in acetic (20).…”

“…The antitumor properties of 1,2,4-triazole and 1,3,4-thiadiazole derivatives [20] prompted us to synthesize thiadiazole derivative incorporated with triazole moiety to enhance its antitumor activity. Thus, multicomponent reaction of 1 with isatin and thiosemicarbazide in acetic (20). The formation of structure 20 was explained via condensation of 1 with isatin to give ketimine intermediate 20′ followed by cycloaddition of thiosemicarbazide gave intermediate 20 00 , then cyclocondensation reaction followed by acetylation of intermediate 20′′′ in Scheme 5.…”

Novel Aldimine‐Type Schiff Bases of 4‐Amino‐5‐[(3,4,5‐trimethoxyphenyl)methyl]‐1,2,4‐triazole‐3‐thione/thiol: Docking Study, Synthesis, Biological Evaluation, and Anti‐Tubulin Activity

“…Due to the considerable biological activities of the five-membered ring 1,2,4-triazoles like analgesic, antimicrobial, antitubercular, anti-inflammatory, and antineoplastic activities [16][17][18][19], this heterocycle and their derivatives have been incorporated into a wide variety of therapeutically interesting drugs among which vorozole, letrozole, and anastrozole (as aromatase inhibitor) are currently being used for the treatment of breast cancer [16,20]. Literature review revealed the antitumor and tumor-associated carbonic anhydrase (isoenzymes I, II, and IX) inhibitory activities of the thione-and thiol-substituted 1,2,4-triazole ring systems [16,21,22]. In addition, the inhibitory activity of substituted 1,2,4-triazoles-5-thione toward the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) has been reported by Abou-Seri et al [23].…”

One‐Pot Synthesis of New Thiadiazolyl‐Pyridines as Anticancer and Antioxidant Agents

“…Substituted 1,3,4-thiadiazoles have attracted considerable interest owing to their wide spectrum biological activity, including antimicrobial, antituberculosis, anesthetic, antithrombotic, anticonvulsant, antihypertensive, anti-inflammatory, and antiulcer activities [1][2][3][4][5]. Moreover, researchers reported 1, 3, 4-thiadiazole derivatives that exhibited anticancer activities with excellent 50% growth inhibitory concentration (IG 50 ) and 50% inhibitory concentration (IC 50 ) [6][7][8][9][10].…”