Potent and selective 5-LO inhibitor bearing benzothiophene pharmacophore: Discovery of MK-5286

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 24, 2010, Pages 7440-7443

  Li, Lianhai ^a,b   Berthelette, Carl ^a   Chateauneuf, Anne ^a   Ouellet, Marc ^a   Sturino, Claudio F ^a   Wang, Zhaoyin ^a  

^a MERCK FROSST CENTRE FOR THERAPEUTIC RESEARCH   (Canada)

^b NONE   (Canada)

Author keywords

5 Lipoxygenase; Benzothiophene; Inhibitor; MK 5286

Indexed keywords

3 (4 FLUOROPHENYL) 6 [[4-[1 HYDROXY 1 (TRIFLUOROMETHYL)PROPYL] 1H 1,2,3 TRIAZOL 1 YL]METHYL] 1 BENZOTHIOPHENE 2 CARBOXAMIDE; BENZOTHIOPHENE; LIPOXYGENASE INHIBITOR; MK 5286; UNCLASSIFIED DRUG;

ARTICLE; DRUG POTENCY; DRUG SYNTHESIS; PHARMACOPHORE; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; ARACHIDONATE 5-LIPOXYGENASE; DOGS; DRUG EVALUATION, PRECLINICAL; HUMANS; HYDROCARBONS, FLUORINATED; LIPOXYGENASE INHIBITORS; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES; TRIAZOLES;

EID: 78449284865     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.10.024     Document Type: Article

References (15)

1. For a review and references therein, see: J. Rokach, Leukotrienes and Lipoxygenases 1989 Elsevier Amsterdam
2. M. Peters-Golden, and W.R. Henderson Jr. N. Engl. J. Med. 357 2007 1841
3. O. Rdmark, O. Werz, D. Steinhilber, and B. Samuelsson Trends Biochem. Sci. 32 2007 332
4. J.F. Evans, A.D. Ferguson, R.T. Mosley, and J.H. Hutchinson Trends Pharmacol. Sci. 29 2008 72
5. C. Pergola, and O. Werz Expert Opin. Ther. Patents 20 2010 355
6. See M. Mehrabian, H. Allayee, J. Wong, W. Shih, X.-P. Wang, Z. Shaposhnik, C.D. Funk, and A.J. Lusis Circ. Res. 91 2002 120
7. I. Avis, S.H. Hong, A. Martinez, T. Moody, Y.H. Choi, J. Trepel, R. Das, M. Jett, and J.L. Mulshine FASEB J. 15 2001 2007
8. M.R. Yun, H.M. Park, K.W. Seo, S.J. Lee, D.S. Im, and C.D. Kim Free Radic. Res. 44 2010 742
9. W. Berger, M.T. De Chandt, and C.B. Cairns Int. J. Clin. Pract. 61 2007 663
10. Y. Ducharme, M. Blouin, C. Brideau, A. Chateauneuf, Y. Gareau, E.L. Grimm, H. Juteau, S. Laliberte, B. MacKay, F. Masse, M. Ouellet, M. Salem, A. Styhler, and R.W. Friesen ACS Med. Chem. Lett. 1 2010 170 and references therein
11. Unpublished results.
12. Berthelette, C.; Dufresne, C.; Li, L.; Wang, Z. WO2007016784, 2007; 73pp.
13. T. Higa, and A.J. Krubsack J. Org. Chem. 40 1975 3037
14. C. Brideau, C. Chan, S. Charlson, D. Denis, J.F. Evans, A.W. Ford-Hutchinson, R. Fortin, J.W. Gillard, J. Guay, D. Guevremont, J.H. Hutchinson, T.R. Jones, S. Leger, J.A. Mancini, C.S. McFarlane, C. Pickett, H. Piechuta, P. Prasit, D. Riendeau, C.A. Rouzer, P. Tagari, P.J. Vickers, R.N. Young, and W.M. Abraham Can. J. Physiol. Pharmacol. 70 1992 799
15. By hydrolysis of (S)-2l with NaOH.