Design and synthesis of substituted nicotinamides as inhibitors of soluble epoxide hydrolase

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 20, 2009, Pages 5864-5868

  Taylor, Steven J ^a   Soleymanzadeh, Fariba ^a   Eldrup, Anne B ^a   Farrow, Neil A ^a   Muegge, Ingo ^a   Kukulka, Alison ^a   Kabcenell, Alisa K ^a   Lombaert, Stephane De ^a  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

Epoxyeicosatrienoic acids; Inhibitors; Nicotinamides; Soluble epoxide hydrolase

Indexed keywords

2 CHLORO 4 CYANOBENZYLAMINE; 2 CHLORO 4 METHYLSULFONAMIDE BENZYLAMINE; 2 CHLORO 4 METHYLSULFONYLBENZYLAMINE; 2 TRIFLUOROMETHOXY BENZYLAMINE DERIVATIVE; 4 BROMO 2 TRIFLUOROMETHOXY BENZYLAMINE; BENZHYDRYLAMIDE DERIVATIVE; BENZYLAMINE; C (4' METHYLSULFONYLBIPHENYL 4 YL)METHYLAMINE; EPOXIDE HYDROLASE; METHYLSULFONE DERIVATIVE; N METHYLSULFONAMIDE; NICOTINAMIDE DERIVATIVE; PYRIDONE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG DESIGN; DRUG HALF LIFE; DRUG INHIBITION; DRUG METABOLISM; DRUG STRUCTURE; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

ANIMALS; ANTI-INFLAMMATORY AGENTS; BINDING SITES; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; ENZYME INHIBITORS; EPOXIDE HYDROLASES; HUMANS; MICROSOMES, LIVER; NIACINAMIDE; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 70349203774     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.08.074     Document Type: Article

References (29)

1. Fleming I. Circ. Res. 89 (2001) 753
2. Spector A.A., and Norris A.W. Am. J. Physiol. Cell Physiol. 292 (2007) C996
3. Yu Z., Xu F., Huse L.M., Morriseau C., Draper A.J., Newman J.W., Parker C., Graham L., Engler M.M., Hammock B.D., Zeldin D.C., and Kroetz D.L. Circ. Res. 87 (2000) 992
4. 50 of 130 nM in the hSEH enzymatic assay. This LM data could be confounded by the low HT solubility of these analogs, (all <1 μg/mL)
5. Larsen B.T., Miura H., Hatoum O.A., Campbell W.B., Hammock B.D., Zeldin D.C., Falck J.R., and Gutterman D.D. Am. J. Physiol. Heart Circ. Physiol. 290 (2006) H491
6. Spector A.A., Fang X., Snyder G.D., and Weintraub N.L. Prog. Lipid Res. 43 (2004) 55
7. Batchu S.N., Law E., Falck J.R., and Seubert J.M. J. Mol. Cell. Cardiol. 46 (2009) 67
8. Imig J.D., Zhao X., Capdevila J.H., Morisseau C., and Hammock B.D. Hypertension 39 (2002) 690
9. Zhao X., Yamamoto T., Newman J.W., Kim I.-H., Watanabe T., Hammock B.D., Stewart J., Pollock J.S., Pollock D.M., and Imig J.D. J. Am. Soc. Nephrol. 15 (2004) 1244
10. Smith K.R., Pinkerton K.E., Watanabe T., Pedersen T.L., Ma S.J., and Hammock B.D. Proc. Natl. Acad. Sci. U.S.A. 102 (2005) 2186
11. Morisseau C., Goodrow M.H., Dowdy D., Zheng J., Greene J.F., Sanborn J.R., and Hammock B.D. Proc. Natl. Acad. Sci. U.S.A. 96 (1999) 8849
12. Morisseau C., Goodrow M.H., Newman J.W., Wheelock C.E., Dowdy D.L., and Hammock B.D. Biochem. Pharmacol. 63 (2002) 1599
13. Kim I.H., Morisseau C., Watanabe T., and Hammock B.D. J. Med. Chem. 47 (2004) 2110
14. Olearczyk J.J., Field M.B., Kim I.H., Morisseau C., Hammock B.D., and Imig J.D. J. Pharmacol. Exp. Ther. 318 (2006) 1307
15. Kim I.H., Tsai H.J., Nishi K., Kasagami T., Morisseau C., and Hammock B.D. J. Med. Chem. 50 (2007) 5217
16. Hwang S.H., Tsai H.J., Liu J.Y., Morisseau C., and Hammock B.D. J. Med. Chem. 50 (2007) 3825
17. Kim I.H., Heirtzler F.R., Morisseau C., Nishi K., Tsai H.J., and Hammock B.D. J. Med. Chem. 48 (2005) 3621
18. Morisseau C., Goodrow M.H., Dowdy D., Zheng J., Greene J.F., Sanborn J.R., and Hammock B.D. Proc. Natl. Acad. Sci. U.S.A. 96 (1999) 8849
19. Shen H.C., Ding F.-X., Wang S., Xu S., Chen H.S., Tong X., Tong V., Mitra K., Kumar S., Zhang X., Chen Y., Zhou G., Pai L.-Y., Alonso-Galicia M., Chen X., Zhang B., Tata J.R., Berger J.P., and Colletti S.L. Bio. Med. Chem. Lett. 19 (2009) 3398
20. Shen H.C., Ding F.-X., Deng Q., Xu S., Chen H.-S., Tong X., Tong V., Zhang X., Chen Y., Zhou G., Pai L.-Y., Alonso-Galicia M., Zhang B., Roy S., Tata J.R., Berger J.P., and S.L. C. Bio. Med. Chem. Lett. 19 (2009) 5314
21. Gomez G.A., Morisseau C., Hammock B.D., and Christianson D.W. Biochemistry 43 (2004) 4716
22. http://www.aretetherapeutics.com/discovery_seh.html.
23. Taylor, S. J.; et. al. Abstracts of Papers, Part 2, 212th National Meeting of the American Chemical Society, Boston, MA, Aug 25-29, 2007.
24. Eldrup, A.B.; Soleymanzadeh, S.; Taylor, S. J.; Muegge, I.; Farrow, N. A.; Joseph, D.; McKellop, K.; Man, C. C.; De Lombaert, S. J. Med. Chem. in press. This manuscript describes the enzymatic and cellular assays used to determine sEH inhibition. Cywin, C L; De Lombaert, S.; Eldrup, A. B.; Ingraham, R. H.; Taylor, S.; Soleymanzadeh, F. WO 06/121719 November 16, 2006.
25. Ingraham, R.; et al. U.S. Patent 6,794,158, September 21, 2004.
26. Taylor S.J., and Netherton M.A. J. Org. Chem. 71 (2006) 397
27. Ingraham, R. H.; Cardozo, M. G.; Grygon, C. Anne; Kroe, R. Rebecca; Proudfoot, J. R. WO 02/082082.
28. Eldrup, A. B.; Farrow, N. A.; Kowalski, J. A.; De Lombaert, S.; Muegge, I. A.; Soleymanzadeh, F.; Swinamer, A. D.; Taylor, S. J. WO 07/098352 August 30, 2007.
29. An alignment of the rat and human protein sequences reveals that there are several amino-acid differences within the ligand binding site. Many of these changes are close to the region of the protein that would influence the SAR described in Table 2.