- Synthesis and antimicrobial activities of 2-thione-3-substituted-5-(4-carboxycyclohexyl-methyl)-tetrahydro-2H-1, 3, 5-thiadiazine derivatives
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(Formula Presented) In this study, 3-substituted-5-(4-carboxycyclohexyl-methyl)-tetrahydro-2H-1, 3, 5-thiadiazine-2-thione which have phenylethyl (1), octyl (2), cyclopropyl (3), 4-methoxybenzyl (4), phenyl (5) groups in position 3 have been synthesized and examined for antimicrobial activities. Their structures were elucidated by spectral method. Antibacterial activities of these compounds against Gram-positive bacteria (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212), gram-negative bacteria (Escherichia coli ATCC 2592, Pseudomonas aeruginosa ATCC 27853) and yeast-like fungi (Candida albicans ATCC 10231, Candida parapsilosis ATCC 90018) were investigated by the micro-dilution method and compared with the activity of sulbentine, ciprofloxacin and flucanozole. By this way their minimal inhibitory concentration (MIC) values were determinated. Compounds 1-4 exhibited almost equally potent activity against Staphylococcus aureus ATCC 29213 (MIC: 31.2 μg/mL). Compounds 1, 3, 4 showed similar antibacterial activity against Enterococcus faecalis ATCC 29212) (MIC: 62.5 μg/mL). None of the compounds exhibited activity against Gram-negative bacteria. On the other hand, all compounds had potent antifungal activities against the yeast utilized. Compounds 1-4 displayed significant antifungal activity against Candida parapsilosis ATCC 90018 at 7.8 μg/mL concentration while sulbentine was active at 125 μg/mL. Among the synthesized compounds, 3-cyclopropyl-5-(4-carboxycyclohexyl-methyl)-tetrahydro-2H-1, 3, 5-thiadiazine-2-thione(3) seems to be the most effective compound with antibacterial and antifungal activity.
- ?z?elik, Azime Berna,Yilmaz, Günseli,?zkan, Semiha,Ersan, Seyhan
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p. 1059 - 1064
(2016/07/15)
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- Exploring the structure-activity relationships of [1-(4-(4- tert-butyl-3'-hydroxy)benzhydryl-4-benzylpiperazine] (SL-3111), a high-affinity and selective δ-opioid receptor nonpeptide agonist ligand
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SL-3111 [1-(4-tert-butyl-3'-hydroxy)benzhydryl-4- benzylpiperazine] is a de novo designed, high-affinity and selective nonpeptide peptidomimetic agonist of the δ-opioid receptor. In a previous report we had described the unique biological characteristics of this ligand and also a need for further structural evaluation. To pursue this, we have introduced a completely different heterocyclic template (2 and 3), which, based on molecular modeling studies, may present the required structural features to properly orient the pharmacophore groups. We also have made more subtle changes to the original piperazine scaffold (5 and 11). The biological activities of these compounds revealed an important participation of the scaffold in the ligand-receptor interaction. To further explore functional diversity on the scaffold, we have maintained the original piperazine ring and introduced four different functionalities at position 2 of the heterocyclic ring (15a-d; a = CH2-O-CH2-Ph; b = Me; c = CH2Ph; d = CH2OH). The biological activities observed for these compounds showed a very interesting trend in terms of the steric effects of the groups introduced at this position. A decrease of almost 2000-fold in affinity and potency at the δ- receptor was observed for 15c compared with 15b. This difference may be explained if we postulate that the bioactive conformation of these peptidomimetics is close to the minimal energy conformations calculated in our study. On the basis of these findings we have realized the importance of this position to further explore and simplify the structure of future generations of peptidomimetic ligands.
- Alfaro-Lopez, Josue,Okayama, Toru,Hosohata, Keiko,Davis, Peg,Porreca, Frank,Yamamura, Henry I.,Hruby, Victor J.
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p. 5359 - 5368
(2007/10/03)
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- Model for delivery of amines through incorporation into a tetrahydro-2H-1,3,5-thiadiazine-2-thione structure
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Phenethylamine 1a (a; n = 2) and benzylamine 1b (b; n = 1) are known in medicinal chemistry as strong vasopressors.Both are excellent substrates for the enzyme monoamine oxidase (MAO).The 2 compounds were incorporated in a highly lipid-soluble and hydrolysis-vulnerable tetrahydrothiadiazine (THTT) target structure in order to modify their pharmacokinetics.Better partition correlations, expressed as log P (calculated and observed) for the synthesized products THTT in comparison to the original compounds 1a,b have been found.One of the THTT derivatives was tested for its liability for chemical hydrolysis and the structure of the hydrolytic product was determined. tetrahydro-2H-1,3,5-thiadiazine-2-thione / phenethylamine / benzylamine / prodrugs / monoamine oxidase inhibitors / partition coefficient / hydrolysis
- El-Shorbagi, A-Na
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