Minor structural change to tertiary sulfonamide RORC ligands led to opposite mechanisms of action

ACS Medicinal Chemistry Letters

Volumn 6, Issue 3, 2015, Pages 276-281

  René, Olivier ^a   Fauber, Benjamin P ^a   Boenig, Gladys De Leon ^a   Burton, Brenda ^b   Eidenschenk, Céline ^a   Everett, Christine ^a   Gobbi, Alberto ^a   Hymowitz, Sarah G ^a   Johnson, Adam R ^a   Kiefer, James R ^a   Liimatta, Marya ^a   Lockey, Peter ^b   Norman, Maxine ^b   Ouyang, Wenjun ^a   Wallweber, Heidi A ^a   Wong, Harvey ^a  

^a GENENTECH INC   (United States)

^b Argenta Early Discovery Charles River 7 9 Spire Green Centre Flex Meadow   (United Kingdom)

Author keywords

agonist; IL 17; inverse agonist; PBMC; RORc; ROR ; TH17

Indexed keywords

ALDEHYDE; BENZALDEHYDE; BENZYLSULFONAMIDE; CELL NUCLEUS RECEPTOR; INTERLEUKIN 17; LIGAND; RETINOIC ACID RECEPTOR GAMMA; RETINOIC ACID RECEPTOR RELATED ORPHAN RECEPTOR GAMMA; SULFONAMIDE; UNCLASSIFIED DRUG;

AMINATION; ARTICLE; BINDING ASSAY; BINDING SITE; CARBOXY TERMINAL SEQUENCE; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; CYTOKINE PRODUCTION; DRUG RECEPTOR BINDING; EC50; HUMAN; HUMAN CELL; HYDROGEN BOND; INVERSE AGONISM; LIGAND BINDING; LIPOPHILICITY; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN SECONDARY STRUCTURE; STEREOSPECIFICITY;

EID: 84924744510     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml500420y     Document Type: Article

References (28)

1. Hirose, T.; Smith, R. J.; Jetten, A. Biochem. Biophys. Res. Commun. 1994, 205, 1976
2. Ivanov, I. I.; McKenzie, B. S.; Zhou, L.; Takodoro, C. E.; Lepelley, A.; Lafaille, J. J.; Cua, D. J.; Littman, D. R. Cell 2006, 126, 1121
3. Sabat, R.; Ouyang, W.; Wolk, K. Nat. Rev. Drug Disc. 2014, 13, 21
4. Codarri, L.; Gyülvészi, G.; Tosevski, V.; Hesske, L.; Fontana, A.; Magnenat, L.; Suter, T.; Becher, B. Nat. Immunol. 2011, 12, 560
5. Rich, P.; Sigurgeirsson, B.; Thaci, D.; Ortonne, J.-P.; Paul, C.; Schopf, R. E.; Morita, A.; Roseau, K.; Harfst, E.; Guettner, A.; Machacek, M.; Papavassilis, C. Br. J. Dermatol. 2013, 168, 402
6. Chabaud, M.; Durand, J. M.; Buchs, N.; Fossiez, F.; Page, G.; Frappart, L.; Miossec, P. Arthritis Rheum. 1999, 42, 963
7. Lock, C.; Hermans, G.; Pedotti, R.; Brendolan, A.; Schadt, E.; Garren, H.; Langer-Gould, A.; Strober, S.; Cannella, B.; Allard, J.; Klonowski, P.; Austin, A.; Lad, N.; Kaminski, N.; Galli, S. J.; Oksenberg, J. R.; Raine, C. S.; Heller, R.; Steinman, L. Nat. Med. 2002, 8, 500
8. Fujino, S.; Andoh, A.; Bamba, S.; Ogawa, A.; Hata, K.; Araki, Y.; Bamba, T.; Fujiyama, Y. Gut 2003, 52, 65
9. Kojetin, D. J.; Burris, T. P. Nat. Rev. Disc. 2014, 13, 197
10. Fauber, B. P.; Magnuson, S. J. Med. Chem. 2014, 57, 5871
11. Yang, J.; Sundrud, M. S.; Skepner, J.; Yamagata, T. Trends Pharmacol. Sci. 2014, 35, 493
12. For a description of the nomenclature of ROR-family modulators, see: Schupp, M.; Lazar, M. A. J. Biol. Chem. 2010, 285, 40409
13. For a review on NR nomenclature, see: Germain, P.; Staels, B.; Dacquet, C.; Spedding, M.; Laudet, V. Pharmacol. Rev. 2006, 58, 685
14. Solt, L. A.; Griffin, P. R.; Burris, T. P. Curr. Opin. Lipidol. 2010, 21, 204
15. Fauber, B. P.; René, O.; Burton, B.; Everett, C.; Gobbi, A.; Hawkins, J.; Johnson, A. R.; Liimatta, M.; Lockey, P.; Norman, M.; Wong, H. Bioorg. Med. Chem. Lett. 2014, 24, 2182
16. Fauber, B. P.; René, O.; de Leon Boenig, G.; Burton, B.; Deng, Y.; Eidenschenk, C.; Everett, C.; Gobbi, A.; Hymowitz, S. G.; Johnson, A. R.; La, H.; Liimatta, M.; Lockey, P.; Norman, M.; Ouyang, W.; Wanga, W.; Wong, H. Bioorg. Med. Chem. Lett. 2014, 24, 3891
17. For a review on the structure of NRs, see: Huang, P.; Chandra, V.; Rastinejad, F. Annu. Rev. Physiol. 2010, 72, 247
18. Fujita-Sato, S.; Ito, S.; Isobe, T.; Ohyama, T.; Wakabayashi, K.; Morishita, K.; Ando, O.; Isono, F. J. Biol. Chem. 2011, 286, 31409
19. Fauber, B. P.; de Leon Boenig, G.; Burton, B.; Eidenschenk, C.; Everett, C.; Gobbi, A.; Hymowitz, S. G.; Johnson, A. R.; Liimatta, M.; Lockey, P.; Norman, M.; Ouyang, W.; René, O.; Wong, H. Bioorg. Med. Chem. Lett. 2013, 23, 6604
20. Jiang, L.; Buchwald, S. Palladium-Catalyzed Aromatic Carbon-Nitrogen Bond Formation. In Metal-Catalyzed Cross-Coupling Reactions, 2 nd ed.; de Meijere, A.; Diederich, F., Eds.; Wiley-VCH GmbH & Co. KGaA: Weinheim, 2004; Vol. 2, pp 699-760.
21. For representative synthetic protocols, see: Fauber, B. P.; René, O. WO 2013/092941.
22. Leeson, P. D.; Springthorpe, B. Nat. Rev. Drug Disc. 2007, 6, 881
23. Leach, A. R.; Hann, M. M.; Burrows, J. N.; Griffen, E. J. Mol. BioSyst. 2006, 2, 429
24. The logP was calculated with internal software using the VolSurf approach. For additional details, see: Cruciani, G.; Crivori, P.; Carrupt, P.- A.; Testa, B. THEOCHEM 2000, 503, 17
25. Salonen, L. M.; Ellermann, M.; Diederich, F. Angew. Chem., Int. Ed. 2011, 50, 4808
26. Another team has noted similar effects with RORc inverse agonists. For details, see: Yang, T.; Liu, Q.; Cheng, Y.; Cai, W.; Ma, Y.; Yang, L.; Wu, Q.; Orband-Miller, L. A.; Zhou, L.; Xiang, Z.; Huxdorf, M.; Zhang, W.; Zhang, J.; Xiang, J.-N.; Leung, S.; Qiu, Y.; Zhong, Z.; Elliott, J. D.; Lin, X. ACS Med. Chem. Lett. 2014, 5, 65
27. Fleming, F. F.; Yao, L.; Ravikumar, P. C.; Funk, L.; Shook, B. C. J. Med. Chem. 2010, 53, 7902
28. Parkin, A.; Collins, A.; Gilmore, C. J.; Wilson, C. C. Acta Crystallogr., Sect. B: Struct. Sci. 2008, 64, 66