Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Synthesis and Biological Activity of [[(Heterocycloamino)alkoxy] benzyl]-2,4-thiazolidinediones as $PPAR_\gamma$ Agonists

  • Jeon Raok (College of Pharmacy, Sookmyung Women's University) ;
  • Kim Yoon-Jung (College of Pharmacy, Sookmyung Women's University) ;
  • Cheon Ye-Jin (College of Pharmacy, Sookmyung Women's University) ;
  • Ryu Jae-Ha (College of Pharmacy, Sookmyung Women's University)
  • Published : 2006.05.01
Download PDF
⟨ Previous Next ⟩

Abstract

Benzothiazole derivatives of thiazolidinediones (TZD) were synthesized using a modified Mitsunobu reaction of 2-(benzothiazol-2-ylmethylamino)ethanol (2) with 5-(4-hydroxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione and assayed for activity on peroxisome proliferator-activated receptor (PPAR) subtypes and inhibitory activity of NO production in lipopolysaccharide-activated macrophages. Most of the tested compounds were identified as potent $PPAR_\gamma$ agonists, indicating their potential as drug candidates for diabetes.

Keywords

References

  1. Cantello, B. C., Cawthorne, M. A., Cottam, G. P., Duff, P. T., Haigh, D., Hindley, R. M., Lister, C. A., Snith, S. A., and Thurlby, P. L., [[${\omega}$-(Heterocyclylamino)alkoxy]benzyl]-2,4- thiazolidinediones as potent antihyperglycemic agents. J. Med. Chem., 37, 3977-3985 (1994) https://doi.org/10.1021/jm00049a017
  2. Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S., and Tannenbaum, S. R., Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal. Biochem., 126, 131-138 (1982) https://doi.org/10.1016/0003-2697(82)90118-X
  3. Heneka, M. T., Feinstein, D. L., Galea, E., Gleichmann, M., Wullner, U., and Klockgether, T., Peroxisome proliferatoractivated receptor gamma agonists protect cerebellar granule cells from cytokine-induced apoptotic cell death by inhibition of inducible nitric oxide synthase. Journal of Neuroimmunology, 100, 156-168 (1999) https://doi.org/10.1016/S0165-5728(99)00192-7
  4. Henke, B. R., Blanchard, S. G., Brackeen, M. F., Brown, K. K., Cobb, J. E., Collins, J. L. Jr., Harrington, W. W., Hashim, M. A., Hull-Ryde, E. A., Kaldor, I., Kliewer, S. A., Lake, D. H., Leesnitzer, L. M., Lehmann, J. M., Lenhard, J. M., Orband- Miller, L. A., Miller, J. F., Mook, R. A. Jr., Noble, S. A., Oliver, W. Jr., Parks, D. J., Plunket, K. D., Szewczyk, J. R., and Willson, T. M., N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel series of potent antihyperglycemic and antihyperlipidemic agents. J. Med. Chem., 41, 5020-5036 (1998) https://doi.org/10.1021/jm9804127
  5. Jeon, R. and Park, S., Synthesis and biological activity of benzoxazole containing thiazolidinedione derivatives. Arch. Pharm. Res., 27, 1099-1105 (2004) https://doi.org/10.1007/BF02975111
  6. Lehmann, J. M., Moorre, L. B., Smith-Oliver, T. A., Wilkinson, W. O., Wilson, T. M., and Kliewer, S. A., An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$. J. Biol. Chem., 270, 12953-12956 (1995) https://doi.org/10.1074/jbc.270.22.12953
  7. Lohray, B. B., Bhushan, V., Rao, B. P., Madhavan, G. R., Murali, N., Rao, K. N., Reddy, A. K., Rajesh, B. M., Reddy, P. G., Chakrabarti, R., Vikramadithyan, R. K., Rajagopalan, R., Mamidi, R. N., Jajoo, H. K., and Subramaniam, S., Novel euglycemic and hypolipidemic agents. 1. J. Med. Chem., 41, 1619-1630 (1998) https://doi.org/10.1021/jm970444e
  8. Morita, H., Mori, H., and Kobayashi, Y., Process for the production of a thiazolidinedione derivative, GB 2324089A (1998)
  9. Oguchi, M., Wada, K., Honma, H., Tanaka, A., Kaneko, T., Sakakibara, S., Ohsumi, J., Serizawa, N., Fujiwara, T., Horikoshi, H., and Fujita, T., Molecular design, synthesis, and hypoglycemic activity of a series of thiazolidine-2,4-diones. J. Med. Chem., 43, 3052-3066 (2000) https://doi.org/10.1021/jm990522t
  10. Reaven, G. M., Chang, H., and Hoffman, B. B., Additive hypoglycemic effects of drugs that modify free-fatty acid metabolism by different mechanisms in rats with streptozocin-induced diabetes. Diabetes, 37, 28-32 (1988) https://doi.org/10.2337/diabetes.37.1.28
  11. Sohda, T., Momose, Y., Meguro, K., Kawamatsu, Y., Sugiyama, Y., and Ikeda, H., Studies on antidiabetic agents. Synthesis and hypoglycemic activity of 5-[4-(pyridylalkoxy)benzyl]-2,4- thiazolidinediones. Arzneim.-Forsch., 40, 37-42 (1990)
  12. Yoshioka, T., Fujita, T., Kanai, T., Aizawa, Y., Kurumada, T., Hasegawa, K., and Horikoshi, H., Studies on hindered phenols and analogues. 1. Hypolipidemic and hypoglycemic agents with ability to inhibit lipid peroxidation. J. Med. Chem., 32, 421-428 (1989) https://doi.org/10.1021/jm00122a022