New Quinoxaline Derivatives as Potential MT1 and MT2 Receptor Ligands
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Pharmacology and Structure-Activity Relationship
Quinoxalines | Comp. | R | MT1 Ki (µM) ± SEM | MT2 Ki (µM) ± SEM |
---|---|---|---|---|
3a | CH3 | 2.98 ± 0.36 | 0.88 ± 0.30 | |
3b | CH2CH3 | 2.60 ± 0.23 | 0.66 ± 0.01 | |
3c | CH2CH2CH3 | 0.75 ± 0.36 | 1.10 ± 0.03 | |
3d | CH(CH3)2 | 1.23 ± 0.32 | 0.47 ± 0.02 | |
3e | Ph | >103 | >103 | |
3f | NHCH2CH3 | >103 | 0.40 ± 0.13 | |
3g | NHCH2CH2CH3 | >103 | 0.44 ± N.D. | |
3h | NHCH(CH3)2 | >103 | >103 | |
3i | NHPh | >103 | >103 | |
6a | CH3 | 20.00 ± 1.82 | 0.08 ± N.D. | |
6b | CH2CH3 | 17.60 ± 7.81 | 4.36 ± 1.22 | |
6c | CH2CH2CH3 | 11.50 ± 2.80 | 1.35 ± 0.31 | |
6d | CH(CH3)2 | 3.40 ± 1.37 | 10.50 ± 2.96 | |
6e | Ph | >103 | >103 | |
6f | NHCH2CH3 | 3.41 ± 1.89 | 28.80 ± N.D | |
6g | NHCH2CH2CH3 | 1.63 ± 0.44 | 0.489 ± 0.07 | |
6h | NHCH(CH3)2 | >103 | >103 | |
6i | NHPh | >103 | >103 | |
10a | CH3 | >103 | >103 | |
10b | CH2CH3 | >103 | 0.34 ± 0.15 | |
10c | CH2CH2CH3 | 0.21 ± 0.11 | 0.10 ± 0.01 | |
10d | CH(CH3)2 | 0.32 ± 0.04 | 0.16 ± 0.00 | |
10e | Ph | >103 | >103 | |
MLT | 0.14·× 10−3 ± 0.03·× 10−3 | 0.41·× 10−3 ± 0.04·× 10−3 |
Compound | MT2 | |
---|---|---|
EC50 ± SEM (μM) | Emax ± SEM (%) | |
MLT | 0.49 ×·10−3 ± 0.05·× 10−3 | 100 |
6a | >10 | |
6c | 1.3 ± 0.26 | 84 ± 9.5 |
3. Experimental
3.1. Chemical Synthesis
3.1.1. General Remarks
3.1.2. Synthesis of 2-Chloro-3-methoxyquinoxaline (1)
3.1.3. Synthesis of 3-Methoxyquinoxaline-2-carbonitrile (2)
3.1.4. General Procedure for Synthesis of N-(3-Methoxyquinoxalin-2-ylmethyl)-alkylamidea 3a–e
3.1.5. General Procedure for Synthesis of 1-Alkyl-3-(3-methoxyquinoxalin-2-ylmethyl)ureas 3f–i
3.1.6. Synthesis of 2,3-Dimethoxy-6-nitroquinoxaline (4)
3.1.7. Synthesis of 6-Amino-2,3-dimethoxyquinoxaline (5)
3.1.8. General Procedure for Synthesis of N-(2,3-Dimethoxyquinoxalin-6-yl)alkylamides 6a–e
3.1.9. General Procedure for Synthesis of 1-(2,3-Dimethoxyquinoxaline-6-yl)-3-alkylureas 6f–i
3.1.10. Synthesis of 3-Amino-7-methoxy-1,4-di-N-oxidequinoxaline-2-carbonitrile (7)
3.1.11. Synthesis of 7-Methoxy-1,4-di-N-oxidequinoxaline-2-carbonitrile (8)
3.1.12. Synthesis of 7-Methoxyquinoxaline-2-carbonitrile (9)
3.1.13. General Procedure for Synthesis of N-[(7-Methoxyquinoxalin-2-yl)methyl]alkylamides 10a–e
3.2. Pharmacology
3.2.1. Reagents and Chemicals
3.2.2. Cell Culture
3.2.3. Binding Assays
4. Conclusions
Acknowledgments
References and Notes
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Ancizu, S.; Castrillo, N.; Pérez-Silanes, S.; Aldana, I.; Monge, A.; Delagrange, P.; Caignard, D.-H.; Galiano, S. New Quinoxaline Derivatives as Potential MT1 and MT2 Receptor Ligands. Molecules 2012, 17, 7737-7757. https://doi.org/10.3390/molecules17077737
Ancizu S, Castrillo N, Pérez-Silanes S, Aldana I, Monge A, Delagrange P, Caignard D-H, Galiano S. New Quinoxaline Derivatives as Potential MT1 and MT2 Receptor Ligands. Molecules. 2012; 17(7):7737-7757. https://doi.org/10.3390/molecules17077737
Chicago/Turabian StyleAncizu, Saioa, Nerea Castrillo, Silvia Pérez-Silanes, Ignacio Aldana, Antonio Monge, Philippe Delagrange, Daniel-Henry Caignard, and Silvia Galiano. 2012. "New Quinoxaline Derivatives as Potential MT1 and MT2 Receptor Ligands" Molecules 17, no. 7: 7737-7757. https://doi.org/10.3390/molecules17077737