The discovery of 2-anilinothiazolones as 11β-HSD1 inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 22, 2007, Pages 6056-6061

  Yuan, Chester ^a   St Jean Jr , David J ^a   Liu, Qingyian ^a   Cai, Lynn ^a   Li, Aiwen ^a   Han, Nianhe ^a   Moniz, George ^a   Askew, Ben ^a   Hungate, Randall W ^a   Johansson, Lars ^b   Tedenborg, Lars ^b   Pyring, David ^b   Williams, Meredith ^b   Hale, Clarence ^a   Chen, Michelle ^a   Cupples, Rod ^a   Zhang, Jiandong ^a   Jordan, Steven ^a   Bartberger, Michael D ^a   Sun, Yaxiong ^a   Emery, Maurice ^a   Wang, Minghan ^a   Fotsch, Christopher ^a   more..

^a AMGEN INC   (United States)

^b BIOVITRUM AB   (Sweden)

Author keywords

11 HSD1; 11 Hydroxysteroid dehydrogenase type 1; Metabolic syndrome; Thiazolone

Indexed keywords

11BETA HYDROXYSTEROID DEHYDROGENASE 1 INHIBITOR; 2 ANILINOTHIAZOLONE DERIVATIVE; ENZYME INHIBITOR; HUMAN SERUM ALBUMIN; THIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; NONHUMAN; RAT; REACTION ANALYSIS; STRUCTURE ANALYSIS; X RAY CRYSTALLOGRAPHY;

11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1; ANIMALS; CHLORINE; CHO CELLS; CRICETINAE; CRICETULUS; CRYSTALLOGRAPHY, X-RAY; FLUORINE; HUMANS; MOLECULAR STRUCTURE; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES;

RATTUS;

EID: 35148832557     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.09.070     Document Type: Article

References (38)

1. Moller D.E., and Kaufman K.D. Annu. Rev. Med. 56 (2005) 45
2. Arnaldi G., Angeli A., Atkinson A.B., Bertagna X., Cavagnini F., Chrousos G.P., Fava G.A., Findling J.W., Gaillard R.C., Grossman A.B., Kola B., Lacroix A., Mancini T., Mantero F., Newell-Price J., Nieman L.K., Sonino N., Vance M.L., Giustina A., and Boscaro M. J. Clin. Endocrinol. Metab. 88 (2003) 5593
3. Seckl J.R., and Walker B.R. Trends Endocrinol. Metab. 15 (2004) 418
4. Kannisto K., Pietilainen K.H., Ehrenborg E., Rissanen A., Kaprio J., Hamsten A., and Yki-Jarvinen H. J. Clin. Endocrinol. Metab. 89 (2004) 4414
5. Tomlinson J.W., Walker E.A., Bujalska I.J., Draper N., Lavery G.G., Cooper M.S., Hewison M., and Stewart P.M. Endocr. Rev. 25 (2004) 831
6. Stewart P.M., Wallace A.M., Valentino R., Burt D., Shackleton C.H.L., and Edwards C.R.W. Lancet 2 (1987) 821
7. Masuzaki H., Paterson J., Shinyama H., Morton N.M., Mullins J.J., Seckl J.R., and Flier J.S. Science 294 (2001) 2166
8. Kotelevtsev Y., Holmes M.C., Burchell A., Houston P.M., Schmoll D., Jamieson P., Best R., Brown R., Edwards C.R.W., Seckl J.R., and Mullins J.J. Proc. Natl. Acad. Sci. U.S.A. 94 (1997) 14924
9. Morton N.M., Holmes M.C., Fiévet C., Staels B., Tailleux A., Mullins J.J., and Seckl J.R. J. Biol. Chem. 276 (2001) 41293
10. Morton N.M., Paterson J.M., Masuzaki H., Holmes M.C., Staels B., Fievet C., Walker B.R., Flier J.S., Mullins J.J., and Seckl J.R. Diabetes 53 (2004) 931
11. Kershaw E.E., Morton N.M., Dhillon H., Ramage L., Seckl J.R., and Flier J.S. Diabetes 54 (2005) 1023
12. Wang M. Curr. Opin. Invest. Drugs 7 (2006) 319
13. Hermanowski-Vosatka A., Balkovec J.M., Cheng K., Chen H.Y., Hernandez M., Koo G.C., LeGrand C.B., Li Z., Metzger J.M., Mundt S.S., Noonan H., Nunes C.N., Olson S.H., Pikounis B., Ren N., Robertson N., Schaeffer J.M., Shah K., Springer M.S., Strack A.M., Strowski M., Wu K., Wu T., Xiao J., Zhang B.B., Wright S.D., and Thieringer R. J. Exp. Med. 202 (2005) 517
14. Wang M. Drug Dev. Res. 67 (2006) 567
15. St. Jean Jr. D.J., Yuan C., Bercot E.A., Cupples R., Chen M., Fretland J., Hale C., Hungate R.W., Komorowski R., Veniant M., Wang M., Zhang X., and Fotsch C. J. Med. Chem. 50 (2007) 429
16. Rohde J.J., Pliushchev M.A., Sorensen B.K., Wodka D., Shuai Q., Wang J., Fung S., Monzon K.M., Chiou W.J., Pan L., Deng X., Chovan L.E., Ramaiya A., Mullally M., Henry R.F., Stolarik D.F., Imade H.M., Marsh K.C., Beno D.W.A., Fey T.A., Droz B.A., Brune M.E., Camp H.S., Sham H.L., Frevert E.U., Jacobson P.B., and Link J.T. J. Med. Chem. 50 (2007) 149
17. Patel J.R., Shuai Q., Dinges J., Winn M., Pliushchev M., Fung S., Monzon K., Chiou W., Wang J., Pan L., Wagaw S., Engstrom K., Kerdesky F.A., Longenecker K., Judge R., Qin W., Imade H.M., Stolarik D., Beno D.W.A., Brune M., Chovan L.E., Sham H.L., Jacobson P., and Link J.T. Bioorg. Med. Chem. Lett. 17 (2007) 750
18. Richards S., Sorensen B., Jae H., Winn M., Chen Y., Wang J., Fung S., Monzon K., Frevert E.U., Jacobson P., Sham H., and Link J.T. Bioorg. Med. Chem. Lett. 16 (2006) 6241
19. Yeh V.S.C., Kurukulasuriya R., Fung S., Monzon K., Chiou W., Wang J., Stolarik D., Imade H., Shapiro R., Knourek-Segel V., Bush E., Wilcox D., Nguyen P.T., Brune M., Jacobson P., and Link J.T. Bioorg. Med. Chem. Lett. 16 (2006) 5555
20. Yeh V.S.C., Patel J.R., Yong H., Kurukulasuriya R., Fung S., Monzon K., Chiou W., Wang J., Stolarik D., Imade H., Beno D., Brune M., Jacobson P., Sham H., and Link J.T. Bioorg. Med. Chem. Lett. 16 (2006) 5414
21. Yeh V.S.C., Kurukulasuriya R., Madar D., Patel J.R., Fung S., Monzon K., Chiou W., Wang J., Jacobson P., Sham H.L., and Link J.T. Bioorg. Med. Chem. Lett. 16 (2006) 5408
22. Yeh V.S.C., Kurukulasuriya R., and Kerdesky F.A. Org. Lett. 8 (2006) 3963
23. Schuster D., Maurer E.M., Laggner C., Nashev L.G., Wilckens T., Langer T., and Odermatt A. J. Med. Chem. 49 (2006) 3454
24. Gu X., Dragovic J., Koo G.C., Koprak S.L., LeGrand C., Mundt S.S., Shah K., Springer M.S., Tan E.Y., Thieringer R., Hermanowski-Vosatka A., Zokian H.J., Balkovec J.M., and Waddell S.T. Bioorg. Med. Chem. Lett. 15 (2005) 5266
25. Olson S., Aster S.D., Brown K., Carbin L., Graham D.W., Hermanowski-Vosatka A., LeGrand C.B., Mundt S.S., Robbins M.A., Schaeffer J.M., Slossberg L.H., Szymonifka M.J., Thieringer R., Wright S.D., and Balkovec J.M. Bioorg. Med. Chem. Lett. 15 (2005) 4359
26. Barf T., Vallågrda J., Emond R., Häggström C., Kurz G., Nygren A., Larwood V., Mosialou E., Axelsson K., Olsson R., Engblom L., Edling N., Rönquist-Nii Y., Öhman B., Alberts P., and Abrahmsén L. J. Med. Chem. 45 (2002) 3813
27. Fotsch C., Askew B.C., and Chen J.J. Expert Opin. Ther. Pat. 15 (2005) 289
28. Henriksson M., Homan E., Johansson L., Vallgarda J., Williams M., Bercot E., Fotsch C.H., Li A., Cai G., Hungate R.W., Yuan C.C., Tegley C., St. Jean D., Han N., Huang Q., Liu Q., Bartberger M.D., Moniz G.A., and Frizzle M.J. WO 2005116002 Chem. Abstr. 144 (2005) 36327
29. See Ref. 27 for a description of the 11β-HSD1 and 2 binding Assay.
30. See Ref. 27 for a description of the 11β-HSD1 whole cell assay.
31. For a description of the methods used in our laboratory, see:. Zhang J., Osslund T.D., Plant M.H., Clogston C.L., Nybo R.E., Xiong F., Delaney J.M., and Jordan S.R. Biochemistry 44 (2005) 6948
32. 32
33. The tautomeric equilibria of N-substituted thiazolones appear highly dependent on the nature of the substituent. A detailed study of tautomerism in this and other related systems, along with ramifications of ligand binding, will be published in due course.
34. Chelli R., Gervasio F.L., Procacci P., and Schettino V. J. Am. Chem. Soc. 124 (2002) 6133
35. Sinnokrot M.O., and Sherrill C.D. J. Am. Chem. Soc. 126 (2004) 7690
36. Kim K.W., Wang Z., Busby J., Tsuruda T., Chen M., Hale C., Castro V.M., Svensson S., Nybo R., Xiong F., and Wang M. Biochim. Biophys. Acta, Proteins Proteomics 1764 (2006) 824
37. 3OH; column: Chiralpak AD-H (250 × 21 mm, 5 μm); flow rate: 65 mL/min; column temp: 40 °C.
38. Compounds 3-5 are racemates and it is possible that the single enantiomers may have different PK. However, the protein shift was not significantly different for the separated enantiomers.