Metabolic activation of N-thiazol-2-yl benzamide as glucokinase activators: Impacts of glutathione trapping on covalent binding

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 5, 2010, Pages 1619-1622

  Iino, Tomoharu ^a   Hashimoto, Noriaki ^a   Hasegawa, Takuro ^a   Chiba, Masato ^a   Eiki, Jun ichi ^a   Nishimura, Teruyuki ^a  

^a BANYU PHARMACEUTICAL CO LTD   (Japan)

Author keywords

Covalent binding; Glucokinase activator; GSH trapping; Radio labeled compound

Indexed keywords

ANTIDIABETIC AGENT; BENZAMIDE DERIVATIVE; GLUCOKINASE ACTIVATOR; GLUTATHIONE; N THIAZOL 2 YL BENZAMIDE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; COVALENT BOND; DRUG METABOLISM; HUMAN; HUMAN CELL; IN VITRO STUDY; INCUBATION TIME; LIVER MICROSOME; NONHUMAN; OXIDATION; RAT;

ANIMALS; BENZAMIDES; BIOTRANSFORMATION; ENZYME ACTIVATION; GLUCOKINASE; GLUTATHIONE; HUMANS; HYPOGLYCEMIC AGENTS; MICROSOMES, LIVER; RATS; SULFONES; THIAZOLES;

EID: 76649144776     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.01.041     Document Type: Article

References (32)

1. Printz R.L., Magnuson M.A., and Granner D.K. Annu. Rev. Nutr. 13 (1993) 463
2. Matschinsky F.M. Diabetes 45 (1996) 223
3. Matschinsky F.M., Glaser B., and Magnuson M.A. Diabetes 47 (1998) 307
4. Futamura M., Hosaka H., Kadotani A., Shimazaki H., Shimazaki H., Sasaki K., Ohyama S., Nishimura T., Eiki J., and Nagata Y. J. Biol. Chem. 281 (2006) 37668
5. Sarabu R., and Grimsby J. Curr. Opin. Drug Discov. Devel. 8 (2005) 631
6. Grimsby J., Sarabu R., Corbett W.L., Haynes N.E., Bizzarro F.T., Coffey J.W., Guertin K.R., Hilliard D.W., Kester R.F., Mahaney P.E., Marcus L., Qi L.D., Spence C.L., Tengi J., Magnuson M.A., Chu C.A., Dvorozniak M.T., Matschinsky F.M., and Grippo J.F. Science 301 (2003) 370
7. Efanov A.M., Barrett D.G., Brenner B.M., Briggs S.L., Delaunois A., Durbin J.D., Giese U., Guo H., Radloff M., Sanz G.G., Sewing S., Wang Y., Weichert A., Zaliani A., and Gromada J. Endocrinology 136 (2005) 2696
8. Coope G.J., Atkinson A.M., Allott C., McKerrecher D., Johnstone C., Pike K.G., Holme P.C., Vertigan H., Gill D., Coghlan M.P., and Leightton B. Br. J. Pharmacol. 149 (2006) 328
9. McKerrecher D., Allen J.V., Caulkett P.W.R., Donald C.S., Fenwick M.L., Grange E., Johnson K.M., Johnstone C., Jones C.D., Pike K.G., Rayner J.W., and Walker R.P. Bioorg. Med. Chem. Lett. 16 (2006) 2705
10. Daniewski, A. R.; Liu, W.; Radinov, R. N. WO Patent 2007/115968.
11. Sarabu R., Berthel S.J., Kester R.F., and Tilley J.W. Expert Opin. Ther. Patents 18 (2008) 759
12. Bertram L.S., Black D., Briner P.H., Chatfield R., Cooke A., Fyfe M.C.T., Murray P.J., Naud F., Nawano M., Procter M.J., Rakipovski G., Rasamison C.M., Reynet C., Schofield K.L., Shah V.K., Spindler F., Taylor A., Turton R., Williams G.M., Wong-Kai-In P., and Yasuda K. J. Med. Chem. 51 (2008) 4340
13. Nishimura T., Iino T., Mitsuya M., Bamba M., Watanabe H., Tsukahara D., Kamata K., Sasaki K., Ohyama S., Hosaka H., Futamura M., Nagata Y., and Eiki J. Bioorg. Med. Chem. Lett. 19 (2009) 1357
14. Iino T., Tsukahara D., Kamata K., Sasaki K., Ohyama S., Hosaka H., Hasegawa T., Chiba M., Nagata Y., Eiki J., and Nishimura T. Bioorg. Med. Chem. 17 (2009) 2733
15. Iino T., Hashimoto N., Sasaki K., Ohyama S., Yoshimoto R., Hosaka H., Hasegawa T., Chiba M., Nagata Y., Eiki J., and Nishimura T. Bioorg. Med. Chem. 17 (2009) 3800
16. Mitsuya M., Kamata K., Bamba M., Watanabe H., Sasaki Y., Sasaki K., Ohyama S., Hosaka H., Nagata Y., Eiki J., and Nishimura T. Bioorg. Med. Chem. Lett. 19 (2009) 2718
17. Ishikawa M., Nonoshita K., Ogino Y., Nagae Y., Tsukahara D., Hosaka H., Maruki H., Ohyama S., Yoshimoto R., Sasaki K., Nagata Y., Eiki J., and Nishimura T. Bioorg. Med. Chem. Lett. 19 (2009) 4450
18. Takahashi K., Hashimoto N., Nakama C., Kamata K., Sasaki K., Yoshimoto R., Ohyama S., Hosaka H., Maruki H., Nagata Y., Eiki J., and Nishimura T. Bioorg. Med. Chem. 17 (2009) 7042
19. Iino T., Sasaki Y., Bamba M., Mitsuya M., Ohno A., Kamata K., Hosaka H., Maruki H., Futamura M., Yoshimoto R., Ohyama S., Sasaki K., Chiba M., Ohtake N., Nagata Y., Eiki J., and Nishimura T. Bioorg. Med. Chem. Lett. 19 (2009) 5531
20. Kamata K., Mitsuya M., Nishimura T., Eiki J.I., and Nagata Y. Structure 12 (2004) 429
21. Evans D.C., Watt A.P., Nicoll-Griffith D.A., and Baillie T.A. Chem. Res. Toxicol. 17 (2004) 3
22. Day S.H., Mao A., White R., Schulz-Utermoehl T., Miller R., and Beconi M.G. J. Pharmacol. Toxicol. Methods 52 (2005) 278
23. Chauret N., Nicoll-Griffith D., Friesen R., Li C., Trimble L., Dube D., Fortin R., Girard Y., and Yergey J. Drug Metab. Dispos. 23 (1995) 1325
24. Pohl L.R., and Branchflower R.V. Methods Enzymol. 77 (1981) 43
25. Scheigetz J., Berthelette C., Li C., and Zamboni R.J. J. Labelled Compd. Radiopharm. 47 (2004) 881
26. To a solution of compound 3 (1.0 mg) in THF (0.5 mL) containing DBU (5 μl) was added tritiated water (200 μl, 5 Ci/mL). The mixture was stirred in a closed vial at room temperature for overnight. To the mixture was added ethyl acetate (2 mL) and 1 N HCl (1 mL) containing saturated brine. The mixture was partitioned, dried and concentrated. The crude residue was purified by preparative HPLC to afford tritiated compound 3 (yield: ca. 0.7 mg, specific activity: 102.2 mCi/mmol, total activity: 165.8 μCi, purity: >99.4% (radio HPLC, 210 nm).
27. We have shown experimentally in house by radiometric HPLC that no back exchange of tritium at methyl sulfone moiety and no metabolism at the site of tritiation was taking place.
28. Compound 3 (10 μM, 50 mCi/mmol) was added to a phosphate-buffered solution (100 mM; pH 7.4) containing 1 mg/mL of rat or human liver microsomes. Following a 15 min pre-incubation at 37 °C, NADPH (1 mM) or phosphate buffer was added (final incubation volume of 200 μL) and a 60 min incubation was carried out at 37 °C. Then, samples were quenched with acetone, the precipitated proteins were collected and washed using a Brandel cell harvester, and the presence of radiolabeled material bound to microsomal proteins was measured by scintillation counting after protein solubilization.
29. Compound 3 (10 μM) and 1 mg microsomal proteins/mL in phosphate buffer (pH 7.4) were incubated for 1 h at 37 °C.
30. Hobbs D.C., and Twomey T.M. Drug Metab. Dispos. 5 (1977) 75
31. Onderwater R.C.A., Commandeur J.N.M., Menge W.M.P.B., and Vermeulen N.P.E. Chem. Res. Toxicol. 12 (1999) 396
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