| Autor: |
Nimkar, S. K., Mabic, S., Anderson, A. H., Palmer, S. L., Graham, T. H., Jonge, M. de, Hazelwood, L., Hislop, S. J., Castagnoli, N., Jr. |
| Zdroj: |
Journal of Medicinal Chemistry; May 20, 1999, Vol. 42 Issue: 10 p1828-1835, 8p |
| Abstrakt: |
The substrate properties of a series of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinyl (MPTP) analogues in which the C-4 phenyl group has been replaced with various 4-azaaryl moieties have been examined in an effort to evaluate the contribution of electronic, polar, and steric parameters to the MAO-B-catalyzed oxidation of this type of cyclic tertiary allylamine to the corresponding dihydropyridinium metabolite. No significant correlation could be found with the calculated energy of the C−H bond undergoing cleavage. A general trend, however, was observed between the magnitude of the log P value with the magnitude of kcat/Km. The results indicate that the placement of a polar nitrogen atom in the space occupied by the phenyl group of MPTP leads to a dramatic decrease in substrate properties. Enhanced substrate properties, however, were observed when benzoazaarenes replaced the corresponding five-membered azaarenes. These results are consistent with our previously published molecular model of the active site of MAO-B. |
| Databáze: |
Supplemental Index |
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