Substituted Amides of Pyrazine-2-carboxylic acids: Synthesis and Biological Activity
Abstract
:Introduction
Results and Discussion
Compd. | MIC [μg ml-1] | % Inhibition | IC50[mmol dm-3] | log P |
---|---|---|---|---|
2a | >6.25 | 0 | 1.072 | 2.72 ± 0.41 |
2b | >6.25 | 0 | 0.440 | 3.28 ± 0.40 |
2c | >6.25 | 0 | 0.244 | 4.41 ± 0.42 |
2d | >6.25 | 28 | 0.486 | 2.72 ± 0.41 |
2e | >6.25 | 11 | 0.148 | 3.28 ± 0.40 |
2f | >6.25 | 24 | 0.118 | 4.41 ± 0.42 |
2g | >6.25 | 6 | -a | 2.15 ± 0.42 |
2h | >6.25 | 18 | 0.286 | 2.72 ± 0.41 |
2i | >6.25 | 7 | 0.097 | 3.84 ± 0.43 |
2j | >6.25 | 19 | 0.313 | 3.46 ± 0.48 |
2k | >6.25 | 39 | 0.081 | 4.03 ± 0.48 |
2l | >6.25 | 20 | 0.107 | 5.15 ± 0.50 |
2m | >6.25 | 12 | 0.026 | 5.16 ± 0.54 |
2n | >6.25 | 10 | 0.114 | 5.73 ± 0.53 |
2o | >6.25 | 72 | 0.241 | 6.85 ± 0.55 |
2p | >6.25 | 0 | 0.649 | 3.18 ± 0.41 |
2q | >6.25 | 2 | 0.229 | 3.75 ± 0.40 |
2r | >6.25 | 13 | 0.242 | 4.87 ± 0.42 |
RMP | 0.125 | 100 | - | − 0.37 ± 0.35 |
DCMUc | - | - | 0.0019 | 2.78 ± 0.38 |
Compd. | IC50[mmol dm-3] | log P |
---|---|---|
2f | 0.063 | 4.41 ± 0.42 |
2l | 0.067 | 5.15 ± 0.50 |
2m | 0.125 | 5.16 ± 0.54 |
2n | 0.208 | 5.73 ± 0.53 |
2o | 0.356 | 6.85 ± 0.55 |
2p | 0.079 | 3.18 ± 0.41 |
DCMU | 0.0073 | 2.78 ± 0.38 |
Acknowledgements.
Experimental
General
Synthesis of amides 2a-r
Compd. | X | R | Y | Formula | % Calculated / % Found | M.p./±C |
---|---|---|---|---|---|---|
M. w. | C H N F Cl Br | Yield/% | ||||
2a | Cl | H | 2-CH3 | C12H10ClN3O | 58.19 4.07 16.97 - 14.31 - | 97-99 |
247.7 | 58.02 4.14 16.86 - 14.19 - | 75 | ||||
2b | H | (CH3)3C | 2-CH3 | C16H19N3O | 71.35 7.11 15.60 - - - | 80-81 |
269,3 | 71.48 7.08 15.67 - - - | 84 | ||||
2c | Cl | (CH3)3C | 2-CH3 | C16H18ClN3O | 63.26 5.97 13.83 - 11.67 - | 114-15 |
303.8 | 63.15 5.82 13.96 - 11.86 - | 78 | ||||
2d | Cl | H | 3-CH3 | C12H10ClN3O | 58.19 4.07 16.97 - 14.31 - | 83-84 |
247.7 | 58.08 4.11 16.80 - 14.48 - | 79 | ||||
2e | H | (CH3)3C | 3-CH3 | C16H19N3O | 71.35 7.11 15.60 - - - | 94-95 |
269,3 | 71.41 7.22 15.77 - - - | 85 | ||||
2f | Cl | (CH3)3C | 3-CH3 | C16H18ClN3O | 63.26 5.97 13.83 - 11.67 - | 98-99 |
303.8 | 63.40 6.08 14.01 - 11.74 - | 84 | ||||
2g | Cl | H | 2-OCH3 | C12H10ClN3O2 | 54.66 3.82 15.94 - 13.45 - | 71-72 |
263.7 | 54.57 3.93 16.01 - 13.35 - | 85 | ||||
2h | H | (CH3)3C | 2-OCH3 | C16H19N3O2 | 67.35 6.71 14.73 - - - | 77-78 |
285.3 | 67.16 6.68 14.62 - - - | 88 | ||||
2i | Cl | (CH3)3C | 2-OCH3 | C16H18ClN3O2 | 60.09 5.67 13.14 - 11.09 - | 118-19 |
319.8 | 60.16 5.59 13.23 - 11.07 - | 82 | ||||
2j | Cl | H | 3-Br | C11H7BrClN3O | 42.27 2.26 13.44 - 11.34 25.56 | 99-100 |
312.5 | 42.37 2.25 13.41 - 11.48 25.60 | 83 | ||||
2k | H | (CH3)3C | 3-Br | C15H16BrN3O | 53.91 4.83 12.57 - - 23.91 | 113-14 |
334.2 | 54.03 4.97 12.61 - - 23.77 | 75 | ||||
2l | Cl | (CH3)3C | 3-Br | C15H15BrClN3O | 48.87 4.10 11.40 - 9.62 21.67 | 104-105 |
368.7 | 48.79 4.22 11.28 - 9.77 21.78 | 62 | ||||
2m | Cl | H | 3,5-CF3 | C13H6ClF6N3O | 42.24 1.64 11.37 30.84 9.59 - | 132-133 |
369.7 | 42.21 1.66 11.33 30.77 9.46 - | 88 | ||||
2n | H | (CH3)3C | 3,5-CF3 | C17H15F6N3O | 52.18 3.86 10.74 29.13 - - | 135-137 |
391.3 | 52.02 3.84 10.72 29.17 - - | 89 | ||||
2o | Cl | (CH3)3C | 3,5-CF3 | C17H14ClF6N3O | 47.96 3.31 9.87 26.77 8.33 - | 98-99 |
425.8 | 48.01 3.41 9.63 26.56 8.51 - | 88 | ||||
2p | Cl | H | 2,6-CH3 | C13H12ClN3O | 59.66 4.62 16.06 - 13.55 - | 121-122 |
361.7 | 59.70 4.70 16.09 - 13.67 - | 75 | ||||
2q | H | (CH3)3C | 2,6-CH3 | C17H21N3O | 72.06 7.47 14.83 - - - | 84-85 |
283.4 | 72.09 7.45 14.84 - - - | 78 | ||||
2r | Cl | (CH3)3C | 2,6-CH3 | C17H20ClN3O | 64.25 6.34 13.22 - 11.16 - | 145-146 |
317.8 | 64.19 6.40 13.18 - 11.17 - | 68 |
Compd. | IR (cm-1) | 1H-NMR (δ, ppm; J in Hz) |
---|---|---|
2a | 1692 (C=O) 3377 (NH) | 2.40s (CH3), 7.10-7.17m (H5´), 7.22-7.33m (H3´- H4´), 8.11-8.15m (H6´), 8.81s (H5), 9.40s (H3), 9.42bs (NH) |
2b | 1685 (C=O) 3358 (NH) | 1.45s [C(CH3)3], 2.40s (CH3), 7.10td (J=7.70, H5´), 7.20-7.33m (H3´- H4´), 8.26d J=7.70, H6´), 8.65dd (J=1.37, H5), 9.41dd (J=1.37, H3), 9.71bs (NH) |
2c | 1695 (C=O) 3360 (NH) | 1.56s [C(CH3)3], 2.40s (CH3), 7.12td (J=7.41, 1.37, H5´), 7.21-7.32m (H3´-H4´), 8.18-8.13m (H6´), 9.28s (H3), 9.42s (NH) |
2d | 1692 (C=O) 3369 (NH) | 2.39s (CH3), 6.98-7.03m (H6´), 7.28t (J=7.96, H5´), 7.52-7.61m (H2´-H4´), 8.80s (H5), 9.35bs (NH), 9.39bs (H3) |
2e | 1684 (C=O) 3356 (NH) | 1.45s[C(CH3)3], 2.38s(CH3), 6.98d (J=7.69, H6´), 7.27t (J=7.69, H5´), 7.50-7.56m (H4´), 7.61-7.65m (H2´), 8.62d (J=1.51, H6), 9.40d (J=1.51,H3), 9.61s (NH) |
2f | 1694 (C=O) 3374 (NH) | 1.55s [C(CH3)3], 2.39s (CH3), 6.97-7.02m (H6´), 7.28t (J=7.69, H5´), 7.51-7.57m (H4´), 7.59-7.63m (H2´), 9.27s (H3), 9.32bs (NH) |
2g | 1690 (C=O) 3377 (NH) | 3.97s (OCH3), 6.94dd (J=7.96, 1.64, H3´), 7.03td (J=7.69, 1.51, H5´), 7.13td (J=7.69, 1.51, H4´), 8.52dd (J=7.96, 1.64, H6´), 8.78s (H5), 9.38s (H3), 10.04s (NH) |
2h | 1691 (C=O) 3356 (NH) | 1.45s [C(CH3)3], 3.96s (OCH3), 6.94dd (J=7.96, 1.64, H3´), 7.02td (J=7.69, 1.53, H5´), 7.11td (J=7.69, 1.53, H4´), 8.59dd (J=7.96, 1.64, H6´), 8.68d (J=1.37, H6), 9.39d (J=1.37, H3), 10.27bs (NH) |
2i | 1695 (C=O) 3369 (NH) | 1.55s [C(CH3)3], 3.97s (OCH3), 6.94dd (J=7.97, 1.51, H3´), 7.02td (J=7.97, 1.51, H5´), 7.12td (J=7.97, 1.51, H4´), 8.53dd (J=7.97, 1.51, H6´), 9.26s (H3), 10.01bs (NH) |
2j | 1701 (C=O) 3369 (NH) | 7.35-7.22m (H5´, H6´), 7.67ddd (J=7.96, 1.92, 1.37, H4´), 8.01t (J=1.92, H2´), 8.82s (H5), 9.38bs (H3), 9.38bs (NH) |
2k | 1692 (C=O) 3352 | 1.45s [C(CH3)3], 7.21-7.32m (H5´,H6´), 7.66dt (J=7.65, 1.92, H4´), 8.03t (J=1.92, H2´), 8.62d (J=1.65, H6), 9.38d (J=1.65, H3), 9.66bs (NH) |
2l | 1697 (C=O) 3360 (NH) | 1.55s [C(CH3)3], 7.22-7.34m (H5´, H6´), 7.66dt (J=7.69, 1.92, H4´), 8.02t (J=1.92, H2´), 9.26s (H3), 9.36bs (NH) |
2m | 1681 (C=O) 3368 (NH) | 7.70bs (H4´), 8.87bs (H5, H2´, H6´) 9.41s (H3), 9.66bs (NH) |
2n | 1699 (C=O) 3346 (NH) | 1.46s[C(CH3)3], 7.66bs (H4´), 8.28bs (H2´, H6´), 8.64d (J=1.51, H6), 9.41d (J=1.51, H3), 9.94bs (NH) |
2o | 1686 (C=O) 3370 (NH) | 1.56s[C(CH3)3], 7.68bs (H4´), 8.29bs (H2´, H6´), 9.29s (H3), 9.63bs (NH) |
2p | 1691 (C=O) 3356 (NH) | 2.28s (CH3), 7.10-7.21m (H3´, H4´, H5´), 8.83s (H5), 8.94bs (NH), 9.39s (H3) |
2q | 1667 (C=O) 3370 (NH) | 1.46s [C(CH3)3], 2.29s (CH3), 7.09-7.19m (H3´, H4´, H5´), 8.65d (J=1.37, H6), 9.16bs (NH), 9.40d (J=1.37, H3) |
2r | 1710 (C=O) 3291 (NH) | 1.57s [C(CH3)3], 2.28s (CH3), 7.07-7.20m (H3´, H4´, H5´), 8.91bs (NH), 9.27s (H3) |
Compd. | 13C NMR (75 MHz, CDCl3) δ, ppm, J in Hz |
---|---|
2a | 159.3, 147.5, 147.4, 144.2, 142.1, 134.9, 130.6, 128.6, 127.0, 125.5, 121.9, 17.6 |
2b | 167.7, 160.9, 142.9, 141.7, 139.1, 135.5, 130.4, 127.9, 126.9, 124.8, 121.4, 37.0, 29.7, 17.6 |
2c | 164.5, 159.7, 145.7, 141.3, 140.2, 135.1, 130.5, 128.5, 126.9, 125.3, 121.7, 39.0, 28.2, 17.6 |
2d | 159.2, 147.4, 147.4, 144.0, 142.2, 139.2, 136.7, 129.0, 126.0, 120.5, 117.1, 21.5 |
2e | 167.6, 161.0, 142.9, 141.5, 139.1, 138.9, 137.3, 128.9, 125.4, 120.3, 116.8, 37.0, 29.7, 21.5 |
2f | 164.4, 159.7, 145.7, 141.2, 140.2, 139.1, 137.0, 128.9, 125.7, 120.5, 117.0, 39.0, 28.3, 21.5 |
2g | 159.2, 148.7, 147.5, 147.3, 144.5, 142.1, 126.6, 124.8, 121.1, 120.0, 110.1, 55.9 |
2h | 167.4, 161.0, 148.6, 142.9, 141.9, 139.2, 127.2, 124.2, 121.1, 119.7, 110.1, 55.8, 37.0, 29.7 |
2i | 164.2, 159.7, 148.7, 145.8, 141.6, 140.1, 126.9, 124.6, 121.0, 119.9, 110.1, 55.9, 38.9, 28.3 |
2j | 159.4, 147.8, 147.5, 143.5, 142.2, 138.1, 130.5, 128.1, 122.9, 122.8, 118.4, 29.7 |
2k | 168.1, 161.1, 143.0, 141.0, 139.0, 138.7, 130.4, 127.5, 122.8, 122.6, 118.1, 37.1, 29.7 |
2l | 164.9, 159.9, 145.8, 140.7, 140.3, 138.3, 130.4, 127.9, 122.8, 118.4, 39.0, 28.2 |
2m | 159.9, 148.4, 147.7, 142.9, 142.4, 138.3, 132.7 (q, J=33.5 Hz), 123.0 (q, J=272.8 Hz), 119.7, 118.5 (q, J=3.7 Hz) |
2n | 168.7, 161.6, 143.2, 140.3, 139.1, 138.9, 132.6 (q, J=33.7 Hz), 123.1 (q, J=272.9 Hz), 119.4 (d, J=2.9 Hz), 117.8 (q, J=3.8 Hz), 37.2, 29.7 |
2o | 165.6, 160.4, 146.0, 140.4, 140.0, 138.5, 132.6 (q, J=33.2 Hz), 123.0 (q, J=272.9 Hz), 119.6 (q, J=3.2 Hz), 118.1 (q, J=4.0 Hz), 39.2, 28.2 |
2p | 159.8, 147.5, 143.9, 142.3, 135.3, 132.7, 128.3,, 127.7, 30.9, 18.5 |
2q | 167.6, 161.4, 143.0, 141.4, 139.1, 135.3, 133.3, 128.2, 127.4, 37.0, 29.7, 18.5 |
2r | 164.5, 160.2, 145.9, 141.0, 140.3, 135.4, 132.9, 128.3, 127.6, 39.0, 28.3, 18.5 |
Antimycobacterial Assay
In vitro antifungal susceptibility testing
Study of inhibition of oxygen evolution rate in spinach chloroplasts
Study of inhibition of chlorophyll production in green algae Chlorella vulgaris
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Dolezal, M.; Miletin, M.; Kunes, J.; Kralova, K. Substituted Amides of Pyrazine-2-carboxylic acids: Synthesis and Biological Activity. Molecules 2002, 7, 363-373. https://doi.org/10.3390/70300363
Dolezal M, Miletin M, Kunes J, Kralova K. Substituted Amides of Pyrazine-2-carboxylic acids: Synthesis and Biological Activity. Molecules. 2002; 7(3):363-373. https://doi.org/10.3390/70300363
Chicago/Turabian StyleDolezal, Martin, Miroslav Miletin, Jiri Kunes, and Katarina Kralova. 2002. "Substituted Amides of Pyrazine-2-carboxylic acids: Synthesis and Biological Activity" Molecules 7, no. 3: 363-373. https://doi.org/10.3390/70300363