Design, Synthesis, and Biological Evaluation of Novel 4-Substituted 1-Methyl-1,2,3,6-tetrahydropyridine Analogs of MPTP

Journal of Medicinal Chemistry

Volumn 35, Issue 23, 1992, Pages 4473-4478

  Zhao, Zhiyang ^a   Dalvie, Deepak ^a   Castagnoli, Kay ^a   Castagnoli, Neal ^a   Naiman, Noreen ^b  

^a VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY   (United States)

^b NORTH CAROLINA STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENOXYPYRIDINE; 1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME B; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL MODIFICATION; DRUG ACTIVITY; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME SUBSTRATE; HYDROLYSIS; NONHUMAN; PRIORITY JOURNAL;

1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; ANIMAL; CATTLE; HYDROLYSIS; LIVER; MONOAMINE OXIDASE; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, P.H.S.;

EID: 0026450944     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm00101a026     Document Type: Article

References (20)

1. Langston, J. W. Mechanisms underlying neuronal degeneration in Parkinson's Disease: An experimental and theoretical treatise. Movement Disorders Suppl. 1. 1989, 4, S15-S25.
2. Chiba, K.; Trevor, A.; Castagnoli, N., Jr. Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase. Biochem. Biophys. Res. Commun. 1984,120, 574-578.
3. Salach, J. I.; Singer, T. P.; Castagnoli, N., Jr.; Trevor, A. Oxidation of the neurotoxic amine l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), by MAO A and B and suicide inactivation of the enzymes by MPTP. Biochem. Biophys. Res. Commun. 1984,125, 831-835.
4. Javitch, J. A.; D'Amato, R. J.; Strittmatter, S. M.; Synder, S. H. Parkinsonism inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: Uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurone explains selective toxicity. Proc. Natl. Acad. Sci. U.S.A. 1985, 82, 2173-2177.
5. Ramsay, R. R.; Dadgar, J.; Trevor, A.; Singer, T. P. Energy-driven uptake of N-methyl-4-phenylpyridine by brain mitochondria mediates the neurotoxicity of MPTP. Life Sci. 1986, 39, 581-585.
6. Nicklas, W. J.; Youngster, S. K.; Kindt, M. V.; Heikkila, R. E. Molecular mechanisms of MPTP induced toxicity. MPTP, MPP+ and mitochondrial function. Life Sci. 1986, 40, 721-729.
7. Maret, G.; Testa, B.; Jenner, P.; Tayar, N. E.; Carrupt, P.-A. The Story: MAO activates tetrahydropyridine derivatives to toxins causing Parkinsonism. Drug Metab. Rev. 1990, 22, 291-332.
8. Youngster, S. K.; Sonsalla, P. K.; Heikkila, R. E. Evaluation of Nbiological activity of several analogs of the dopaminergic neurotoxin MPTP. J. Neurochem. 1987, 48, 929-934.
9. Youngster, S. K.; McKeown, K. A.; Jin, Y.-Z.; Ramsay, R. R.; Heikkila, R. E.; Singer, T. P. Oxidation of analogs of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by monoamine oxidases A and B and the inhibition of monoamine oxidases by the oxidation products. J. Neurochem. 1989, 53, 1837-1842.
10. Naiman, N.; Rollema, H.; Johnson, E.; Castagnoli, N., Jr. Studieson 4-benzyl-1-methyl-1,2,3,6-tetrahydropyridine, a neurotoxic analog of Parkinsonian inducing agent l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Chem. Res. Toxicol. 1990, 3, 133-138.
11. Knoll, J. Deprenyl (Selegyline): The history of its development and pharmacological action. Acto Neurol. Scand. 1983, Suppl. 95, 57-80.
12. Subramanyam, B.; Woolf, T.; Castagnoli, N., Jr. Studies on invitro conversion of haloperidol to a potentially neurotoxic pyridinium metabolite. Chem. Res. Toxicol. 1991, 4, 123-128.
13. Stütz, P.; Stadler, P. A. A novel approach to cyclic/3-car bonylenamines 7,8 lysergic acid derivatives via the Polonovski reaction. Tetrahedron Lett. 1973, 5095-5098.
14. Leonard, N. J.; Cook, A. G. Unsaturated amines XIV. The mercuric acetate oxidation of substituted pyrrolidines. J. Am. Chem. Soc. 1959, 81, 5627-5631.
15. Efange, S. M. N.; Michelson, R. H.; Remmel, R. P.; Boudreu, R.J.; Dutta, A. K.; Freshler, A. Flexible N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogues: synthesis and monoamine oxidase catalyzed bioactivation. J. Med. Chem. 1990, 33, 3133-3138.
16. Peterson, L. A.; Caldera, P.; Trevor, A.; Chiba, K.; Castagnoli, N., Jr. Studies on l-methyl-4-phenyl-1,2,3,6-dihydropyridmium species, (2,3-MPDP) the monoamine oxidase catalyzed oxidation product of nigrostriatal toxin l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). J. Med. Chem. 1985, 28, 1432-1436.
17. Eckert, H.; Forster, B. Triphosgene, a crystalline phosgene substitute. Angew. Chem., Int. Ed. Engl. 1987, 26, 894-895.
18. Anderson, P. S.; Lyle, R. E. The mechanism of reduction of pyridinium ions by sodium borohydride. Tetrahedron Lett. 1964,153.
19. Sprague, R. H.; Brooker, L. G. S. Studies in the cyanine dyes series. IX. 4,4′-pyridocyanines and 4-pyrido-4′-cyanines. J.Am.Chem. Soc. 1937, 2697-2699.
20. Lineweaver, H.; Burk, D. The determination of enzyme dissociation constants. J. Am. Chem. Soc. 1934, 56, 658.