Identification of the first inverse agonist of retinoid-related orphan receptor (ROR) with dual selectivity for RORβ and RORγt

Bioorganic and Medicinal Chemistry Letters

Volumn 24, Issue 22, 2014, Pages 5265-5267

  Gege, Christian ^a   Schlüter, Thomas ^a   Hoffmann, Thomas ^a  

^a PHENEX PHARMACEUTICALS AG   (Germany)

Author keywords

2 Aminothiazole; Retinoid related orphan receptor beta; Retinoid related orphan receptor gamma t; ROR ; ROR t

Indexed keywords

7 (3,5 DI TERT BUTYLPHENYL) 3 METHYL 2,4,6 OCTATRIENOIC ACID; HORMONE RECEPTOR STIMULATING AGENT; N (2,2,2 TRIFLUOROETHYL) N [4 (2,2,2 TRIFLUORO 1 HYDROXY 1 TRIFLUOROMETHYLETHYL)PHENYL]BENZENESULFONAMIDE; N [5 (4 CHLORO BENZOYL) 4 (3 CHLOROPHENYL) THIAZOL 2 YL] 2 (4 ETHANESULFONYL PHENYL) ACETAMIDE; RETINOIC ACID; RETINOID RELATED ORPHAN RECEPTOR BETA; RETINOID RELATED ORPHAN RECEPTOR GAMMA; UNCLASSIFIED DRUG; BENZENEACETAMIDE DERIVATIVE; LIGAND; N-(5-(2-CHLOROBENZOYL)-4-(3-CHLOROPHENYL)THIAZOL-2-YL)-2-(4-ETHANESULFONYLPHENYL)ACETAMIDE; PROTEIN BINDING; THIAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; ARTHRITIS; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG LIVER LEVEL; DRUG RECEPTOR BINDING; DRUG SOLUBILITY; DRUG TISSUE LEVEL; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FLUORESCENCE RESONANCE ENERGY TRANSFER; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION; TIME TO MAXIMUM PLASMA CONCENTRATION; AGONISTS; CHEMISTRY; HUMAN; IMMUNOLOGY; INVERSE AGONISM; METABOLISM; TH17 CELL;

BENZENEACETAMIDES; DRUG INVERSE AGONISM; FLUORESCENCE RESONANCE ENERGY TRANSFER; HUMANS; LIGANDS; NUCLEAR RECEPTOR SUBFAMILY 1, GROUP F, MEMBER 2; NUCLEAR RECEPTOR SUBFAMILY 1, GROUP F, MEMBER 3; PROTEIN BINDING; TH17 CELLS; THIAZOLES; TRETINOIN;

EID: 84908439592     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2014.09.053     Document Type: Article

References (30)

1. A.M. Jetten, and J.H. Joo Adv. Dev. Biol. 16 2006 31
2. T.P. Burris, S.A. Busby, and P.R. Griffin Chem. Biol. 19 2012 51
3. S.E. Mullican, J.R. DiSpirito, and M.A. Lazar J. Mol. Endocrinol. 51 2013 T115
4. A.M. Jetten Nucl. Recept. Signal. 7 2009 e003
5. P. Miossec, and J.K. Kolls Nat. Rev. Drug Disc. 11 2012 763
6. J.R. Huh, M.W.L. Leung, P. Huang, D.A. Ryan, M.R. Krout, R.R.V. Malapaka, J. Chow, N. Manel, M. Ciofani, S.V. Kim, A. Cuesta, F.R. Santori, J.J. Lafaille, H.E. Xu, D.Y. Gin, F. Rastinejad, and D.R. Littman Nature 472 2011 486
7. L.A. Solt, N. Kumar, P. Nuhant, Y. Wang, J.L. Lauer, J. Liu, M.A. Istrate, T.M. Kamenecka, W.R. Roush, D. Vidovic, S.C. Schürer, J. Xu, G. Wagoner, P.D. Drew, P.R. Griffin, and T.P. Burris Nature 472 2011 491
8. C. Sherida Nat. Biotechnol. 31 2013 370
9. S.C.P. Williams Nat. Med. 19 2013 1078
10. B.P. Fauber, and S. Magnuson J. Med. Chem. 57 2014 5871
11. http://www.jt.com/investors/results/S-information/pharmaceuticals/index.html.
12. E. André, F. Conquet, M. Steinmayr, S.C. Stratton, V. Porciatti, and M. Becker-André EMBO J. 17 1998 3867
13. L. Jia, E.C.T. Oh, L. Ng, M. Srinivas, M. Brooks, A. Swaroop, and D. Forrest Proc. Natl. Acad. Sci. U.S.A. 106 2009 17534
14. T.M. Kamenecka, B. Lyda, M.R. Chang, and P.R. Griffin MedChemComm 4 2013 764
15. B.P. Fauber, G. de Leon Boenig, B. Burton, C. Eidenschenk, C. Everett, A. Gobbi, S.G. Hymowitz, A.R. Johnson, M. Liimatta, P. Lockey, M. Norman, W. Ouyang, O. René, and H. Wong Bioorg. Med. Chem. Lett. 23 2013 6604
16. J. Skepner, R. Ramesh, M. Trocha, D. Schmidt, E. Baloglu, M. Lobera, T. Carlson, J. Hill, L.A. Orband-Miller, A. Barnes, M. Boudjelal, M. Sundrud, S. Ghosh, and J. Yang J. Immunol. 192 2014 2564
17. B.P. Fauber, O. René, G. de Leon Boenig, B. Burton, Y. Deng, C. Eidenschenk, C. Everett, A. Gobbi, S.G. Hymowitz, A.R. Johnson, H. La, M. Liimatta, P. Lockey, M. Norman, W. Ouyang, W. Wang, and H. Wong Bioorg. Med. Chem. Lett. 24 2014 3891
18. C. Stehlin-Gaon, D. Willmann, D. Zeyer, S. Sanglier, A. Van Dorsselaer, J.P. Renaud, D. Moras, and R. Schüle Nat. Struct. Biol. 10 2003 820
19. P. Huang, V. Chandra, and F. Rastinejad Chem. Rev. 114 2014 233
20. D.P. Marciano, M.R. Chang, C.A. Corzo, D. Goswami, V.Q. Lam, B.D. Pascal, and P.R. Griffin Cell Metab. 19 2014 193
21. Boehm, M. F.; Zhang, L.; Bennani, Y. L.; Nadzan A. M. WO1996020913A1; 1996.
22. D.R. Shalinsky, E.D. Bischoff, W.W. Lamph, L. Zhang, M.F. Boehm, P.J.A. Davies, A.M. Nadzan, and R.A. Heyman Cancer Res. 57 1997 162
23. Wang, Y.; Yang, T.; Liu, Q.; Xiang, J. WO2012028100A1; 2012.
24. Wang, Y.; Cai, W.; Liu, Q.; Xiang, J. WO2012027965A1; 2012.
25. Y. Wang, W. Cai, G. Zhang, T. Yang, Q. Liu, Y. Cheng, L. Zhou, Y. Ma, Z. Cheng, S. Lu, Y.-G. Zhao, W. Zhang, Z. Xiang, S. Wang, L. Yang, Q. Wu, L.A. Orband-Miller, Y. Xu, J. Zhang, R. Gao, M. Huxdorf, J.-N. Xiang, Z. Zhong, J.D. Elliott, S. Leung, and X. Lin Bioorg. Med. Chem. 22 2014 692
26. The c log D was calculated with MarvinView from ChemAxon Ltd.
27. Kinetic solubility (PBS, pH 7.4) was measured at Cerep SA (Celle l'Evescault, France) according to catalog Ref. 0435.
28. N. Kumar, L.A. Solt, J.J. Conkright, Y. Wang, M.A. Istrate, S.A. Busby, R.D. Garcia-Ordonez, T.P. Burris, and P.R. Griffin Mol. Pharmacol. 77 2010 228
29. Kinzel, O.; Steeneck, C.; Kleymann, G.; Albers, M.; Hoffmann, T.; Kremoser, C.; Perovic-Ottstadt, S.; Schlüter, T. WO2011107248A1; 2012.
30. The targets in the 19 human hormone receptors M1H panel are: NR1A1 (TRα), NR1B1 (RARα), NR1C1 (PPARα), NR1C2 (PPARβ), NR1C3 (PPARγ), NR1H2 (LXRβ), NR1H3 (LXRα), NR1H4 (FXR), NR1I1 (VDR), NR1I2 (PXR), NR1I3 (CAR), NR2B1 (RXRα), NR3A1 (ERα), NR3A2 (ERβ), NR3B3 (ERRγ), NR3C1 (GR), NR3C2 (MR), NR3C3 (PR), NR3C4 (AR).