Design, Synthesis and in Vivo Anti-inflammatory Activities of 2,4-Diaryl-5-4H-imidazolone Derivatives
Abstract
:1. Introduction
Approval | 1999 | 1999 | 2001 | 2006 | 2005 |
Withdrawal | ------- | 2004 | 2005 | 2007 | ------- |
Main AEs | ------- | Cardiovascular | Cardiovascular | Hepatotoxicity | ------- |
Authority | FDA | FDA | FDA | EMA, TGA | UK |
2. Results and Discussion
2.1. Rationale and Structure-Based Design
2.2. Chemistry
2.3. Biological Screening
2.3.1. Anti-inflammatory Activity
Tested Compounds | Increase in paw edema (mL) ± SEM a,b | % Protection | Activity relative to indomethacin |
---|---|---|---|
Control | 0.96 ± 0.026 | 0.0 | 0.0 |
Indomethacin | 0.25 ± 0.024 | 74.0 | 100 |
Meloxicam | 0.23 ± 0.019 | 76.0 | 103 |
3-a | 0.32 ± 0.028 | 66.7 | 90 |
3-c | 0.42 ± 0.032 | 56.3 | 76 |
3-d | 0.36 ± 0.016 | 62.5 | 84 |
3-g | 0.31 ± 0.027 | 67.7 | 91 |
3-h | 0.28 ± 0.022 | 70.8 | 96 |
4-a | 0.64 ± 0.026 | 33.3 | 45 |
4-c | 0.73 ± 0.022 | 24.0 | 32 |
4-d | 0.71 ± 0.028 | 26.0 | 35 |
4-g | 0.68 ± 0.032 | 29.2 | 39 |
4-h | 0.49 ± 0.024 | 49.0 | 66 |
5-a | 0.17 ± 0.016 | 82.3 | 111 |
5-c | 0.27 ± 0.023 | 71.9 | 97 |
5-d | 0.20 ± 0.024 | 79.2 | 107 |
5-g | 0.19 ±0.029 | 80.2 | 108 |
5-h | 0.08 ± 0.032 | 91.7 | 124 |
2.3.2. Ulcerogenic Effects
Compound | ED50 (μM/kg) | % Ulceration | Compound | ED50 (μM/kg) | % Ulceration |
---|---|---|---|---|---|
Indomethacin | 9.7 | 100 | 4-d | 29 | 20 |
Meloxicam | 12 | 0 | 4-g | 28 | 20 |
3-a | 23 | 10 | 4-h | 27 | NT |
3-c | 25 | NT | 5-a | 17.9 | 5 |
3-d | 24 | NT | 5-c | 18 | 10 |
3-g | 22 | NT | 5-d | 16.5 | 5 |
3-h | 19.4 | 10 | 5-g | 14.4 | NT |
4-a | 28.7 | 25 | 5-h | 12 | 5 |
4-c | 31 | NT |
2.4. Discussion
3. Experimental
3.1. General
3.2. General Procedure for Preparation 3-[4-Substituted aminosulfonyl)-phenyl]-2-(4-fluorophenyl)-5-arylidene-5(4H)-imidazolones 3–5
3.3. Anti-inflammatory Test
3.4. Ulcerogenicity Test
4. Conclusions
Acknowledgments
- Sample Availability: Contact the authors.
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El-Araby, M.; Omar, A.; Hassanein, H.H.; El-Helby, A.-G.H.; Abdel-Rahman, A.A. Design, Synthesis and in Vivo Anti-inflammatory Activities of 2,4-Diaryl-5-4H-imidazolone Derivatives. Molecules 2012, 17, 12262-12275. https://doi.org/10.3390/molecules171012262
El-Araby M, Omar A, Hassanein HH, El-Helby A-GH, Abdel-Rahman AA. Design, Synthesis and in Vivo Anti-inflammatory Activities of 2,4-Diaryl-5-4H-imidazolone Derivatives. Molecules. 2012; 17(10):12262-12275. https://doi.org/10.3390/molecules171012262
Chicago/Turabian StyleEl-Araby, Moustafa, Abdelsattar Omar, Hassanein H. Hassanein, Abdel-Ghany H. El-Helby, and Asharf A. Abdel-Rahman. 2012. "Design, Synthesis and in Vivo Anti-inflammatory Activities of 2,4-Diaryl-5-4H-imidazolone Derivatives" Molecules 17, no. 10: 12262-12275. https://doi.org/10.3390/molecules171012262