Synthesis and Evaluation of Antidepressant Activities of 5-Aryl-4,5-dihydrotetrazolo [1,5-a]thieno[2,3-e]pyridine Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Pharmacology
2.2.1. Forced Swim Test (FST)
2.2.2. Tail Suspension Test (TST)
2.2.3. Open-Field Test
2.2.4. Determination of 5-HT Concentration
2.2.5. Docking Study
3. Experimental Section
3.1. Chemistry
3.1.1. Synthesis of 7-substitutedphenyl-6,7-dihydrothieno[3,2-b]pyridine-5(4H)-thiones (2a–p)
3.1.2. Synthesis of 5-hydrazono-7-substitutedphenyl-4,5,6,7-tetrahydrothieno[3,2-b]pyridines (3a–p)
3.1.3. Synthesis of 5-aryl-4,5-dihydrotetrazolo[1,5-a]thieno[2,3-e]pyridine (4a–p)
3.1.4. Synthesis of 5-[4-(trifluoromethyl)phenyl]-4,5-dihydrothieno[2,3-e][1,2,4]triazolo[4,3-a]pyridine (5)
3.1.5. Synthesis of 1-methyl-5-[4-(trifluoromethyl)phenyl]-4,5-dihydrothieno[2,3-e][1,2,4]triazolo[4,3-a]pyridine (6)
3.1.6. Synthesis of 5-[4-(trifluoromethyl)phenyl]-4,5-dihydrothieno[2,3-e][1,2,4]triazolo[4,3-a]pyridin-1(2H)-one (7)
3.2. Pharmacology
3.2.1. Evaluation of Antidepressant Activity
3.2.2. Molecular Docking Studies
3.3. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are available from the authors. |
Compound | R | Antidepressant Activities a | |
---|---|---|---|
Duration of Immobility(s) | Change from Control | ||
(mean ± S.E.M.) b | (%) | ||
4a | o-Cl | 87.21 ± 16.95 * | 24.25 |
4b | m-Cl | 99.02 ± 13.12 | 13.99 |
4c | p-Cl | 65.15 ± 12.73 ** | 43.41 |
4d | o-F | 85.22 ± 14.20 * | 25.98 |
4e | m-F | 79.72 ± 19.41 * | 30.76 |
4f | p-F | 53.61 ± 15.50 ** | 53.44 |
4g | o-CF3 | 68.43 ± 11.87 ** | 40.56 |
4h | m-CF3 | 73.63 ± 17.58 ** | 36.05 |
4i | p-CF3 | 51.43 ± 13.76 ** | 55.33 |
4j | o-OCH3 | 95.26 ± 18.83 | 17.26 |
4k | m-OCH3 | 86.54 ± 16.72 * | 24.83 |
4l | p-OCH3 | 66.32 ± 15.61 ** | 42.40 |
4m | p-Br | 83.53 ± 14.23 * | 27.45 |
4n | -H | 78.13 ± 20.91 * | 32.14 |
4o | 2-Cl-6-F | 98.28 ± 16.32 | 14.64 |
4p | 3,4,5-OCH3 | 102.41 ± 19.18 | 11.05 |
5 | p-CF3 | 89.38 ± 12.39 * | 22.37 |
6 | p-CF3 | 93.63 ± 16.81 | 18.70 |
7 | p-CF3 | 82.58 ± 15.15 * | 28.27 |
Fluoxetine | - | 54.21 ± 11.97 ** | 52.91 |
Control | - | 115.13 ± 18.67 | - |
Compound | Dose (mg/kg) | Antidepressant Activities a | |
---|---|---|---|
Duration of Immobility(s) | Change from Control | ||
(mean ± S.E.M.) b | (%) | ||
10 | 81.27 ± 16.13 * | 27.69 | |
4i | 20 | 67.41 ± 14.91 ** | 40.02 |
40 | 53.39 ± 12.85 ** | 52.53 | |
10 | 82.41 ± 15.72 ** | 27.56 | |
Fluoxetine | 20 | 69.18 ± 14.56 ** | 38.44 |
40 | 55.02 ± 10.17 ** | 51.04 | |
Control | - | 112.39 ± 12.14 | - |
Compound | Dose (mg/kg) | Antidepressant Activities a | |
---|---|---|---|
Duration of Immobility (s) | Change from Control | ||
(mean ± S.E.M.) b | (%) | ||
4i | 40 | 72.33 ± 14.61 ** | 43.73 |
Fluoxetine | 40 | 77.18 ± 16.52 ** | 39.95 |
Control | - | 128.54 ± 25.37 | - |
Compound | Dose (mg/kg) | 5-HT (ng/mg) a |
---|---|---|
4i | 40 | 1.276 ± 0.094 *,b |
Fluoxetine | 40 | 1.328 ± 0.105 * |
Control | - | 1.015 ± 0.098 |
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Wang, S.; Liu, H.; Wang, X.; Lei, K.; Li, G.; Quan, Z. Synthesis and Evaluation of Antidepressant Activities of 5-Aryl-4,5-dihydrotetrazolo [1,5-a]thieno[2,3-e]pyridine Derivatives. Molecules 2019, 24, 1857. https://doi.org/10.3390/molecules24101857
Wang S, Liu H, Wang X, Lei K, Li G, Quan Z. Synthesis and Evaluation of Antidepressant Activities of 5-Aryl-4,5-dihydrotetrazolo [1,5-a]thieno[2,3-e]pyridine Derivatives. Molecules. 2019; 24(10):1857. https://doi.org/10.3390/molecules24101857
Chicago/Turabian StyleWang, Shiben, Hui Liu, Xuekun Wang, Kang Lei, Guangyong Li, and Zheshan Quan. 2019. "Synthesis and Evaluation of Antidepressant Activities of 5-Aryl-4,5-dihydrotetrazolo [1,5-a]thieno[2,3-e]pyridine Derivatives" Molecules 24, no. 10: 1857. https://doi.org/10.3390/molecules24101857
APA StyleWang, S., Liu, H., Wang, X., Lei, K., Li, G., & Quan, Z. (2019). Synthesis and Evaluation of Antidepressant Activities of 5-Aryl-4,5-dihydrotetrazolo [1,5-a]thieno[2,3-e]pyridine Derivatives. Molecules, 24(10), 1857. https://doi.org/10.3390/molecules24101857