The Crystal Structure of N-(1-Arylethyl)-4-methyl- 2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides as the Factor Determining Biological Activity Thereof
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemistry
2.2. General Procedure for the Synthesis of N-(1-arylethyl)-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides 3, 4 and 5a
2.3. N-[1-(4-Methoxyphenyl)ethyl]-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide (5b)
2.4. Mechanical Racemic Mixture of Optically Active N-(1-Phenylethyl)-4-methyl-2,2-dioxo-1H-2λ6,1- benzothiazine-3-carboxamides (6a)
2.5. Mechanical Racemic Mixture of Optically Active N-[1-(4-Methoxyphenyl)ethyl]-4-methyl-2,2-dioxo- 1H-2λ6,1-benzothiazine-3-carboxamides (6b)
2.6. X-ray Structural Analysis of N-[(1S)-1-Phenylethyl]-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide (3a)
2.7. X-ray Structural Analysis of N-(1-Phenylethyl)-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide (5a)
2.8. X-ray Structural Analysis of N-[(1S)-1-(4-Methoxyphenyl)ethyl]-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide (3b)
2.9. X-ray Structural Analysis of N-[(1R)-1-(4-Methoxyphenyl)ethyl]-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide (4b)
2.10. X-ray Structural Analysis of N-[1-(4-Methoxyphenyl)ethyl]-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide (5b)
2.11. Pharmacology
Analgesic and Anti-Inflammatory Tests
3. Results and Discussion
3.1. Chemistry
3.2. Evaluation of the Analgesic and Anti-Inflammatory Activity
3.3. The Molecular and Crystal Structure Study
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Entry | Product | Configuration of Chiral Centre | R | Pain Thresholdon Damaged Extremity (g/mm2) | Pain Threshold on Non-Damaged Extremity (g/mm2) | Δ Pain Threshold | Analgesic Activity, Compared to Control (%) |
---|---|---|---|---|---|---|---|
1 | 3a | (S) | H | 514.0 ± 33.2 | 265.0 ± 29.0 | 249.0 ± 22.1 1,2,3 | +21.7 |
2 | 3b | (S) | OMe | 450.0 ± 29.3 | 236.0 ± 15.6 | 214.0 ± 19.0 1,2,3 | +32.7 |
3 | 4a | (R) | H | 369.0 ± 15.0 | 335.2 ± 24.1 | 33.8 ± 5.2 1,2,3 | +89.4 |
4 | 4b | (R) | OMe | 416.0 ± 37.9 | 382.0 ± 32.2 | 34.0 ± 5.5 1,2 | +89.3 |
5 | 5a | (±) | H | 469.0 ± 20.1 | 228.0 ± 10.1 | 241.0 ± 42.2 1,2,3 | +24.2 |
6 | 5b | (±) | OMe | 408.0 ± 10.3 | 333.0 ± 18.5 | 75.0 ± 7.3 1,2,3 | +76.4 |
7 | 6a | (S) & (R) | H | 501.0 ± 54.4 | 282.0 ± 15.4 | 219.0 ± 29.8 1,2 | +31.1 |
8 | 6b | (S) & (R) | OMe | 356.0 ± 15.2 | 186.0 ± 12.6 | 170.0 ± 33.4 1,2 | +46.5 |
9 | Lornoxicam | − | − | 441.0 ± 33.1 | 346.0 ± 30.2 | 95.0 ± 12.7 1 | +70.1 |
10 | Diclofenac | − | − | 538.0 ± 23.6 | 479.0 ± 32.8 | 59.0 ± 15.3 1 | +81.4 |
11 | Control | − | − | 593.0 ± 62.7 | 257.0 ± 41.4 | 318.0 ± 58.2 1 | 0 |
Entry | Product | Configuration of Chiral Centre | R | Volume of Damaged Extremity (mm3) | Volume of Non-Damaged Extremity (mm3) | Δ Volume (Volume Increase) | Anti- Inflammatory Activity, Compared to Control (%) |
---|---|---|---|---|---|---|---|
1 | 3a | (S) | H | 607.8 ± 15.5 | 500.9 ± 17.6 | 106.9 ± 7.7 1,2,3 | +74.2 |
2 | 3b | (S) | OMe | 660.4 ± 47.4 | 311.6 ± 25.1 | 348.7 ± 22.8 1,2,3 | +15.7 |
3 | 4a | (R) | H | 520.9 ± 87.7 | 478.9 ± 87.3 | 41.9 ± 3.6 1,2,3 | +89.9 |
4 | 4b | (R) | OMe | 636.2 ± 74.9 | 552.0 ± 53.8 | 84.2 ± 6.9 1,2,3 | +79.7 |
5 | 5a | (±) | H | 648.6 ± 42.1 | 464.2 ± 13.9 | 184.4 ± 26.3 1,2 | +55.4 |
6 | 5b | (±) | OMe | 535.7 ± 64.3 | 374.5 ± 31.8 | 161.1 ± 19.3 1,2,3 | +61.1 |
7 | 6a | (S) & (R) | H | 687.3 ± 94.0 | 360.5 ± 32.7 | 326.8 ± 59.4 1,2,3 | +21.0 |
8 | 6b | (S) & (R) | OMe | 743.8 ± 98.6 | 379.1 ± 91.6 | 364.6 ± 87.5 1,2,3 | +11.9 |
9 | Lornoxicam | − | − | 360.5 ± 82.5 | 263.9 ± 60.9 | 96.6 ± 22.7 1 | +76.7 |
10 | Diclofenac | − | − | 397.6 ± 22.4 | 306.6 ± 17.6 | 91.0 ± 16.0 1 | +78.0 |
11 | Control | − | − | 768.7 ± 61.0 | 354.9 ± 22.9 | 413.7 ± 72.1 1 | 0 |
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Ukrainets, I.V.; Hamza, G.M.; Burian, A.A.; Voloshchuk, N.I.; Malchenko, O.V.; Shishkina, S.V.; Danylova, I.A.; Sim, G. The Crystal Structure of N-(1-Arylethyl)-4-methyl- 2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides as the Factor Determining Biological Activity Thereof. Sci. Pharm. 2019, 87, 10. https://doi.org/10.3390/scipharm87020010
Ukrainets IV, Hamza GM, Burian AA, Voloshchuk NI, Malchenko OV, Shishkina SV, Danylova IA, Sim G. The Crystal Structure of N-(1-Arylethyl)-4-methyl- 2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides as the Factor Determining Biological Activity Thereof. Scientia Pharmaceutica. 2019; 87(2):10. https://doi.org/10.3390/scipharm87020010
Chicago/Turabian StyleUkrainets, Igor V., Ganna M. Hamza, Anna A. Burian, Natali I. Voloshchuk, Oxana V. Malchenko, Svitlana V. Shishkina, Irina A. Danylova, and Galina Sim. 2019. "The Crystal Structure of N-(1-Arylethyl)-4-methyl- 2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides as the Factor Determining Biological Activity Thereof" Scientia Pharmaceutica 87, no. 2: 10. https://doi.org/10.3390/scipharm87020010