Synthesis of New Visnagen and Khellin Furochromone Pyrimidine Derivatives and Their Anti-Inflammatory and Analgesic Activity
Abstract
:1. Introduction
2. Results and Discussion
2.1. Anti-Inflammatory Activity
Compd. No. | Percent protection | ||
---|---|---|---|
1 hour | 2 hours | 3 hours | |
Visnagen | 38.6 ± 1.38 * | 40.2 ± 1.39 * | 26.2 ± 1.29 * |
Khellin | 40.3 ± 1.40 * | 41.5 ± 1.42 * | 30.4 ± 1.32 * |
1a | 41.5 ± 1.35 * | 40.4 ±1.36 * | 28.2 ± 1.28 * |
1b | 42.6 ± 1.45 * | 41.5 ±1.28 * | 30.1 ± 1.30 * |
2a | 44.5 ± 1.28 * | 43.6 ±1.24 * | 33.1 ± 1.01 * |
2b | 45.7 ± 1.30 * | 44.8 ±1.28 * | 34.2 ± 1.02 * |
3a | 52.6± 1.10 ** | 50.8 ± 1.30 * | 39.4± 1.25 * |
3b | 48.6 ± 1.40 * | 45.6 ±1.40 * | 35.1 ± 1.04 * |
3c | 52.8± 1.12 ** | 52.6 ± 1.10 * | 39.6± 1.23 * |
3d | 49.9 ± 1.50 ** | 48.8 ±1.42 * | 36.5 ± 1.20 * |
4a | 54.4± 1.23 ** | 53.6 ± 1.22 * | 40.4± 1.04 * |
4b | 53.8± 1.20 ** | 52.6 ± 1.10 * | 40.1± 1.02 * |
4c | 55.3 ± 1.25 ** | 54.8 ± 1.24 * | 40.6± 1.05 * |
4d | 54.1± 1.22 ** | 53.2 ± 1.20 * | 40.2± 1.03 * |
5a | 57.9 ± 1.39 ** | 58.9 ± 1.30 * | 41.5 ± 1.08 * |
5b | 57.3 ± 1.37 ** | 58.8 ± 1.29 * | 41.3± 1.06 * |
5c | 58.4 ± 1.40 ** | 59.1 ± 1.31 ** | 42.1 ± 1.23 * |
5d | 57.6 ± 1.38 ** | 60.0 ± 1.68 ** | 41.4 ± 1.07 * |
6a | 59.7 ± 1.45 ** | 59.5 ± 1.35 ** | 42.8 ± 1.26 * |
6b | 59.4 ± 1.05 ** | 59.1 ± 1.31 ** | 42.2 ± 1.24 * |
6c | 59.8 ± 1.52 ** | 59.7 ± 1.45 ** | 45.7 ± 1.52 * |
6d | 59.6 ± 1.41 ** | 59.2 ± 1.32 ** | 42.4 ± 1.25 * |
7a | 61.8± 1.88 ** | 61.4 ± 1.74 ** | 48.2 ± 1.65 * |
7b | 60.5± 1.80 ** | 60.2 ± 1.62 ** | 46.6 ± 1.60 * |
7c | 62.3± 1.92 ** | 61.6 ± 1.78 ** | 48.5 ± 1.68 * |
7d | 60.9± 1.85 ** | 60.4 ± 1.65 ** | 47.1 ± 1.63 * |
Control | 6.3 ± 0.26 | 5.6 ± 0.40 | 3.4 ± 0.96 |
Diclofenac Sodium | 52.6 ± 0.96 * | 60.5± 1.55 ** | 42.2 ± 1.39 * |
2.2. Analgesic Activity
Group | Reaction time (min) | |||
---|---|---|---|---|
0 min | 30 min | 60 min | 90 min | |
Control | 8.25 ± 0.35 | 8.20 ± 0.36 b | 8.75 ± 0.55 b | 9.80 ± 0.48 b |
Visnagen | 5.40 ± 0.56 | 6.30 ± 0.50 | 8.90 ± 0.60 | 9.80 ± 0.25 a |
Khellin | 5.50 ± 0.58 | 6.50 ± 0.40 | 9.01 ± 0.70 | 10.01 ± 0.22 a |
1a | 5.60 ± 0.30 | 6.70± 0.43 | 9.25 ± 0.55 | 10.10 ± 0.20a |
1b | 6.10 ± 0.20 | 7.30 ± 0.10 b | 7.40 ± 0.10 a | 10.20 ± 0.25 a |
2a | 6.20 ± 0.10 | 7.45 ± 0.20 b | 8.10± 0.20 a | 10.50 ± 0.30 a |
2b | 6.40 ± 0.20 | 7.55 ± 0.25 b | 8.25± 0.30 a | 10.80 ± 0.35 a |
3a | 7.01 ± 0.30 | 8.10 ± 0.40 | 10.55 ± 0.50 a | 10.90 ± 0.60 a b |
3b | 6.65 ± 0.10 | 7.90 ± 0.20 b | 8.45 ± 0.50 a | 11.20 ± 0.30 a |
3c | 7.10 ± 0.10 | 8.20 ± 0.30 a | 9.50 ± 0.25 a | 10.55 ± 0.10 a b |
3d | 6.65 ± 0.10 | 7.90 ± 0.20 b | 8.45 ± 0.50 a | 11.20 ± 0.30 a |
4a | 7.85 ± 0.35 | 8.60 ± 0.40 a | 10.01 ± 0.20a | 11.05± 0.40 a b |
4b | 7.30 ± 0.20 | 8.30 ± 0.40 a | 9.80 ± 0.30 a | 10.80 ± 0.20 a b |
4c | 8.10 ± 0.20 | 8.80 ± 0.25 a | 10.10 ± 0.25 a | 11.10 ± 0.30 b |
4d | 7.40 ± 0.30 | 8.50 ± 0.30 a | 9.90 ± 0.35 a | 10.90 ± 0.30 a b |
5a | 8.75 ± 0.60 | 9.10 ± 0.50 a | 10.70 ± 0.40 a | 11.50 ± 0.40 b |
5b | 8.30 ± 0.30 | 8.90 ± 0.30 a | 10.30 ± 0.20 a | 11.20 ± 0.25 b |
5c | 8.95 ± 0.68 | 9.20 ± 0.60 a | 10.90 ± 0.50 a | 11.60 ± 0.30 b |
5d | 8.55 ± 0.50 | 9.01 ± 0.40 a | 10.50 ± 0.30 a | 11.40 ± 0.30 b |
6a | 9.30 ± 0.30 | 9.40 ± 0.30 a | 10.40 ± 0.25 a | 11.10± 0.30 a b |
6b | 9.10 ± 0.30 | 9.20 ± 0.40 a | 10.20 ± 0.20 a | 11.10 ± 0.40a b |
6c | 9.40 ± 0.40 | 9.50 ± 0.30 a | 10.50 ± 0.20 a | 11.20± 0.35 a b |
6d | 9.20 ± 0.20 | 9.30 ± 0.10 a | 10.30 ± 0.30 a | 11.01± 0.20 a b |
7a | 9.70 ± 0.40 | 9.80 ± 0.55 a | 10.75 ± 0.35 a | 11.44± 0.44 a b |
7b | 9.50 ± 0.20 | 9.60 ± 0.40 a | 10.60 ± 0.25 a | 11.30± 0.30 a b |
7c | 9.80 ± 0.50 | 9.95 ± 0.65 a | 10.85 ± 0.45 a | 11.98 ± 0.88 a b |
7d | 9.60 ± 0.30 | 9.70 ± 0.45 a | 10.65 ± 0.30 a | 11.40± 0.40 a b |
Diclofanc sodium | 6.50 ± 0.45 | 10.05 ± 0.15 a | 11.40 ± 0.55 a | 13.18 ± 0.40 a |
Compd. No. | Percent protection | |||
---|---|---|---|---|
30 min | 1 hours | 2 hour | 3 hours | |
Visnagen | 39.20 ± 1.20 * | 44 ± 1.10 * | 48.1 ± 1.70 | 32.20 ± 1.25 * |
Khellin | 40.7 ± 1.65 * | 46 ± 1.35 * | 49.4 ± 1.70 | 33.9 ± 1.10 * |
1a | 42.6 ± 1.40 * | 52 ± 1.25 * | 50.4 ± 1.60 | 35.8 ± 1.39 * |
1b | 45.0 ± 1.90 * | 53 ± 1.40 * | 55.6 ± 1.38 | 36.3 ± 1.20 * |
2a | 46.5 ± 1.50 * | 50 ± 1.10 ** | 52.2 ± 1.30 | 37.5 ± 1.30 * |
2b | 48.2 ± 1.55 * | 52 ± 1.20 * | 54.3 ± 1.25 | 38.7 ± 1.40 * |
3a | 54.6 ± 1.40 * | 58 ± 1.25 * | 62.6 ± 1.20 * | 46.4 ± 1.10 * |
3b | 50.3 ± 1.35 * | 54 ± 1.10 * | 56.4 ± 1.35 | 40.5 ± 1.35 * |
3c | 55.8 ± 1.50 * | 59 ± 1.20 * | 63.6 ± 1.30 * | 47.3 ± 1.30 * |
3d | 52.6 ± 1.35 * | 56 ± 1.05 * | 58.6 ± 1.35 | 42.1 ± 1.40 * |
4a | 60.4 ± 1.40 ** | 63 ± 1.50 ** | 67.7± 1.70 ** | 48.4 ± 1.55 * |
4b | 58.5 ± 1.20 * | 60 ± 1.30 * | 65.4 ± 1.55* | 46.5 ± 1.35 * |
4c | 61.5 ± 1.50 ** | 64 ± 1.55 ** | 68.8 ± 1.80 ** | 49.5 ± 1.60 * |
4d | 59.6 ± 1.30 * | 62 ± 1.40 * | 66.1 ± 1.60 * | 47.3 ± 1.50 * |
5a | 66.50 ± 1.20 ** | 68 ± 1.55 ** | 70.6 ± 1.30 ** | 54.5 ± 1.10 * |
5b | 62.50 ± 1.40 ** | 65 ± 1.35 ** | 69.10 ±1.25 ** | 52.1 ± 1.30 * |
5c | 68.10 ± 1.25 ** | 70 ± 1.85 ** | 71.8 ± 1.35 ** | 55.4 ± 1.05 * |
5d | 65.40 ± 1.10 ** | 67 ± 1.50 ** | 70.20 ±1.15 ** | 53.2 ± 1.20 * |
6a | 69.60 ± 1.55 ** | 72 ± 1.90 ** | 74.3 ± 1.50 ** | 58.8 ± 1.20 * |
6b | 69.1 ± 1.45 ** | 70 ± 1.80 ** | 72.6 ± 1.40 ** | 56.3 ± 1.10 * |
6c | 69.80 ± 1.60 ** | 73 ± 1.95 ** | 75.5 ± 1.55 ** | 59.8 ± 1.19 * |
6d | 69.4 ± 1.50 ** | 71 ± 1.85 ** | 73.5 ± 1.45 ** | 57.5 ± 1.15 * |
7a | 74.4 ± 1.10 ** | 77.5 ± 1.30 ** | 78.3 ± 1.20 | 64.4 ± 1.25 ** |
7b | 70.1 ± 1.01 ** | 75.3 ± 1.50 ** | 76.5 ± 1.25 | 62.4 ± 1.20 ** |
7c | 75.6 ± 1.20 ** | 78.4 ± 1.40 ** | 79.5 ± 1.35 | 65.6 ± 1.30 ** |
7d | 72.2 ± 1.05 ** | 76.2 ± 1.45 ** | 77.6 ± 1.30 | 63.5 ± 1.35 ** |
Control | 02.0 ± 0.36 | 05.0 ± 0.50 | 04.0 ± 0.58 | 04.0 ± 0.90 |
Diclfenac sodium | 45.0 ± 0.96 * | 54.3 ± 1.18 * | 61 ± 1.50 * | 38 ± 1.14 * |
3. Conclusions
4. Experimental
4.1. General
4.2. General Procedure for the Synthesis of 6-((4-Methoxy/4,9-dimethoxy)7-methylfuro[3,2-g]chromen-5-ylideneamino)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-ones 1a,b
4.3. General Procedure for the Synthesis of 6-((4-Methoxy/4,9-dimethoxy)-7-methylfuro[3,2-g]chromen-5-ylideneamino)-2-methylsulfanyl-3H-pyrimidin-4-ones 2a,b
4.4. General Procedure for the Synthesis of 6-((4-Methoxy/4,9-dimethoxy)-7-methylfuro[3,2-g]chromen-5-ylideneamino)-2-(piperazin/morpholin)-1-yl-3H-pyrimidin-4-ones 3a-d
4.5. General Procedure for the Synthesis of (6-Chloro-2-(piperazin/morpholin)-1-yl-pyrimidin-4-yl)-(4-methoxy/4,9-dimethoxy)-7-methylfuro[3,2-g]chromen-5-ylidene)amines 4a-d
4.6. General Procedure for the Synthesis of ((2,6-di-(Piperazin/morpholin))-1-yl-pyrimidin-4-yl)-((4-methoxy/4,9-dimethoxy)-7-methylfuro[3,2-g]chromen-5-ylidene)amines 5a-d
4.7. General Procedure for the Synthesis of 3-Chloro-1-((4-methoxy/4,9-dimethoxy)-7-methyl-5H-furo[3,2-g]chromen-5-yl)-2,4-dimethyl-6,8-di(piperazin/morpholin)-1-yl-1,3,4,6-tetrahydro-2H-pyrim-ido-[1,6-a]pyrimidines 6a-d
4.8. General Procedure for the Synthesis of 1-((4-Methoxy/4,9-dimethoxy)-7-methyl-5H-furo[3,2-g]chromen-5-yl)-2,4-dimethyl-3,6,8-tri-(piperazin/morpholin)-1-yl-1,3,4,6-tetrahydro-2H-pyrimido [1,6-a]pyrimidines 7a-d
5. Biological Evaluation
5.1. Animals
5.2. Anti-Inflammatory Activity (Carrageenan-Induced Rat Hind Paw Edema Model)
5.3. Analgesic Activity Using Hot-Plate Test
5.4. Analgesic Activity (Acetic Acid Induced Writhing Response Model)
Acknowledgements
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Abu-Hashem, A.A.; Youssef, M.M. Synthesis of New Visnagen and Khellin Furochromone Pyrimidine Derivatives and Their Anti-Inflammatory and Analgesic Activity. Molecules 2011, 16, 1956-1972. https://doi.org/10.3390/molecules16031956
Abu-Hashem AA, Youssef MM. Synthesis of New Visnagen and Khellin Furochromone Pyrimidine Derivatives and Their Anti-Inflammatory and Analgesic Activity. Molecules. 2011; 16(3):1956-1972. https://doi.org/10.3390/molecules16031956
Chicago/Turabian StyleAbu-Hashem, Ameen Ali, and Mohamed M. Youssef. 2011. "Synthesis of New Visnagen and Khellin Furochromone Pyrimidine Derivatives and Their Anti-Inflammatory and Analgesic Activity" Molecules 16, no. 3: 1956-1972. https://doi.org/10.3390/molecules16031956