5-Substituted, 6-substituted, and unsubstituted 3-heteroaromatic pyridine analogues of nicotine as selective inhibitors of cytochrome P-450 2A6

Journal of Medicinal Chemistry

Volumn 48, Issue 1, 2005, Pages 224-239

  Denton, Travis T ^a   Zhang, Xiaodong ^a   Cashman, John R ^a  

^a HUMAN BIOMOLECULAR RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [5 (PYRIDIN 3 YL)THIOPHEN 2 YL]ETHANONE; 2 FLUORO 5 (4 METHYLTHIOPHEN 3 YL)PYRIDINE; 2 FLUORO 5 (THIOPHEN 3 YL)PYRIDINE; 3 (1 BENZYL 1H IMIDAZOL 4 YL)PYRIDINE; 3 (1 ETHYL 1H IMIDAZOL 4 YL)PYRIDINE; 3 (1 METHYL 1H IMIDAZOL 4 YL)PYRIDINE; 3 (1 METHYL 1H IMIDAZOL 5 YL)PYRIDINE; 3 (1H IMIDAZOL 4 YL)PYRIDINE; 3 (2 METHYL 1H IMIDAZOL 1 YL)PYRIDINE; 3 (3 METHYLTHIOPHEN 2 YL)PYRIDINE; 3 (4 METHYL 1H IMIDAZOL 1 YL)PYRIDINE; 3 (4 METHYLTHIOPHEN 3 YL)PYRIDINE; 3 (5 METHYL 1H IMIDAZOL 1 YL)PYRIDINE; 3 (PYRIDIN 3 YL)PYRIDINE; 3 (THIOPHEN 2 YL)PYRIDINE; 3 (THIOPHEN 3 YL)PYRIDINE; 5 (PYRIDIN 3 YL)FURAN 2 CARBALDEHYDE OXIME; 5 (PYRIDIN 3 YL)THIOPHEN 2 AMINE; 5 (PYRIDIN 3 YL)THIOPHENE 2 CARBALDEHYDE; 5 (PYRIDIN 3 YL)THIOPHENE 2 CARBALDEHYDE OXIME; [5 (PYRIDIN 3 YL)FURAN 2 YL]METHANAMINE; [5 (PYRIDIN 3 YL)THIOPHEN 2 YL]METHANAMINE; BIS[[5 (PYRIDIN 3 YL)FURAN 2 YL]METHYL]AMINE; BIS[[5 (PYRIDIN 3 YL)THIOPHEN 2 YL]METHYL]AMINE; COUMARIN 7 HYDROXYLASE; CYTOCHROME P450 2A6; CYTOCHROME P450 INHIBITOR; NICOTINE DERIVATIVE; TRIS[[5 (PYRIDIN 3 YL)FURAN 2 YL]METHYL]AMINE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG INHIBITION; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

ARYL HYDROCARBON HYDROXYLASES; BIOCHEMISTRY; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HUMANS; INHIBITORY CONCENTRATION 50; MIXED FUNCTION OXYGENASES; NICOTINE; PYRIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 12144276704     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049696n     Document Type: Article

References (30)

1. Benowitz, N. L. Drug therapy. Pharmacologic aspects of cigarette smoking and nicotine addition. N. Engl. J. Med. 1988, 319, 1318-1330.
2. Vial, W. C. Cigarette smoking and lung disease. Am. J. Med. Sci. 1986, 291, 130-142.
3. Hecht, S. S.; Hoffmann, D. Tobacco-specific nitrosamines, an important group of carcinogens in tobacco and tobacco smoke. Carcinogenesis 1988, 9, 875-884.
4. Doll, R.; Hill, A. B. A study of the etiology of carcinoma of the lung. Br. Med. J. 1952, 2, 1271-1286.
5. Hirayama, T. Non-smoking wives of heavy smokers have a higher risk of lung cancer: a study from Japan. Br. Med. J. 1981, 282, 183-185.
6. Treating Tobacco Use and Dependence. A Clinical Practice Guideline; U.S. Department of Health and Human Services, Public Health Service: Washington, DC, 2000.
7. Scherer, G. Smoking behaviour and compensation: a review of the literature. Psychopharmacology (Berlin) 1999, 145, 1-20.
8. Henningfield, J. E.; Keenan, R. M. Nicotine delivery kinetics and abuse liability. J. Consult. Clin. Psychol. 1993, 61, 743-750.
9. Cashman, J. R.; Park, S. B.; Yang, Z. C.; Wrighton, S. A.; Jacob, P.; Benowitz, N. L. Metabolism of nicotine by human liver microsomes: stereoselective formation of trans-nicotine N′-oxide. Chem. Res. Toxicol. 1992, 5, 639-646.
10. Berkman, C. E.; Park, S. B.; Wrighton, S. A.; Cashman, J. R. In vitro-in vivo correlations of human (S)-nicotine metabolism. Biochem. Pharmacol. 1995, 50, 565-570.
11. Belinsky, S. A.; Devereux, T. R.; Foley, J. F.; Maronpot, R. R.; Anderson, M. W. Role of the alveolar type II cell in the development and progression of pulmonary tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)- 1-butanone in the A/J mouse. Cancer Res. 1992, 52, 3164-3173.
12. Kamataki, T.; Fujita, K.; Nakayama, K.; Yamazaki, Y.; Miyamoto, M.; Ariyoshi, N. Role of human cytochrome P450 (CYP) in the metabolic activation of nitrosamine derivatives: application of genetically engineered Salmonella expressing human CYP. Drug Metab. Rev. 2002, 34, 667-676.
13. Ariyoshi, N.; Miyamoto, M.; Umetsu, Y.; Kunitoh, H.; Dosaka-Akita, H.; Sawamura, Y.; Yokota, J.; Nemoto, N.; Sato, K.; Kamataki, T. Genetic polymorphism of CYP2A6 gene and tobacco-induced lung cancer risk in male smokers. Cancer Epidemiol., Biomarkers Prev. 2002, 11, 890-894.
14. Miyamoto, M.; Umetsu, Y.; Dosaka-Akita, H.; Sawamura, Y.; Yokota, J.; Kunitoh, H.; Nemoto, N.; Sato, K.; Ariyoshi, N.; Kamataki, T. CYP2A6 gene deletion reduces susceptibility to lung cancer. Biochem. Biophys. Res. Commun. 1999, 261, 658-660.
15. Topcu, Z.; Chiba, I.; Fujieda, M.; Shibata, T.; Ariyoshi, N.; Yamazaki, H.; Sevgican, F.; Muthumala, M.; Kobayashi, H.; Kamataki, T. CYP2A6 gene deletion reduces oral cancer risk in betel quid chewers in Sri Lanka. Carcinogenesis 2002, 23, 595-598.
16. Pianezza, M. L.; Sellers, E. M.; Tyndale, R. F. Nicotine metabolism defect reduces smoking. Nature 1998, 393, 750.
17. Rao, Y.; Hoffmann, E.; Zia, M.; Bodin, L.; Zeman, M.; Sellers, E. M.; Tyndale, R. F. Duplications and defects in the CYP2A6 gene: identification, genotyping, and in vivo effects on smoking. Mol. Pharmacol. 2000, 58, 747-755.
18. Benowitz, N. L.; Jacob, P., 3rd Daily intake of nicotine during cigarette smoking. Clin. Pharmacol. Ther. 1984, 35, 499-504.
19. Draper, A. J.; Madan, A.; Parkinson, A. Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. Arch. Biochem. Biophys. 1997, 341, 47-61.
20. Maenpaa, J.; Sigusch, H.; Raunio, H.; Syngelma, T.; Vuorela, P.; Vuorela, H.; Pelkonen, O. Differential inhibition of coumarin 7-hydroxylase activity in mouse and human liver microsomes. Biochem. Pharmacol. 1993, 45, 1035-1042.
21. Zhang, W.; Kilicarslan, T.; Tyndale, R. F.; Sellers, E. M. Evaluation of methoxsalen, tranylcypromine, and tryptamine as specific and selective CYP2A6 inhibitors in vitro. Drug Metab. Dispos. 2001, 29, 897-902.
22. Cai, D.; Larsen, R. D.; Redder, P. J. Effective Lithiation of 3-Bromopyridine: Synthesis of 3-Pyridine Boronic Acid and Variously 3-Substituted Pyridines. Tetrahedron Lett. 2002, 43, 4285-4287.
23. Borch, R. F.; Bernstein, M. D.; Durst, H. D. Cyanohydridoborate Anion as a Selective Reducing Agent. J. Am. Chem. Soc. 1971, 93, 2897-2904.
24. Hazeldine, S. T.; Polin, L.; Kushner, J.; Paluch, J.; White, K.; Edelstein, M.; Palomino, E.; Corbett, T. H.; Horwitz, J. P. Design, synthesis, and biological evaluation of analogues of the antitumor agent, 2-(4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy)propionic acid (XK469). J. Med. Chem. 2001, 44, 1758-1776.
25. Genin, M. J.; Allwine, D. A.; Anderson, D. J.; Barbachyn, M. R.; Emmert, D. E.; Garmon, S. A.; Graber, D. R.; Grega, K. C.; Hester, J. B.; Hutchinson, D. K.; Morris, J.; Reischer, R. J.; Ford, C. W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.; Yagi, B. H. Substituent effects on the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious Gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. J. Med. Chem. 2000, 43, 953-970.
26. Marks, B. D. A high throughput screening assay to screen for CYP2E1 metabolism and inhibition using a fluorogenic Vivid P450 substrate. Assay Drug Dev. Technol. 2002, 1, 73-81.
27. Wood, A. W.; Ryan, D. E.; Thomas, P. E.; Levin, W. Regio- and stereoselective metabolism of two C19 steroids by five highly purified and reconstituted rat hepatic cytochrome P-450 isozymes. J. Biol. Chem. 1983, 258, 8839-8847.
28. Jung, F.; Griffin, K. J.; Song, W.; Richardson, T. H.; Yang, M.; Johnson, E. F. Identification of amino acid substitutions that confer a high affinity for sulfaphenazole binding and a high catalytic efficiency for warfarin metabolism to P450 2C19. Biochemistry 1998, 37, 16270-16279.
29. Cheng, Y.; Prusoff, W. H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50% inhibition (150) of an enzymatic reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
30. Gauthier, D. R.; Szumigala, R. H., Jr.; Dormer, P. G.; Armstrong, J. D., III; Volante, R. P.; Reider, P. J. Synthesis of 5-Pyridyl-2-furaldehydes via Palladium-Catalyzed Cross-Coupling with Triorganozincates. Org. Lett. 2002, 4, 375-378.