Fused tricyclic indoles as S1P 1 agonists with robust efficacy in animal models of autoimmune disease

Bioorganic and Medicinal Chemistry Letters

Volumn 22, Issue 13, 2012, Pages 4404-4409

  Buzard, Daniel J ^a   Han, Sangdon ^a   Lopez, Luis ^a   Kawasaki, Andrew ^a,b   Moody, Jeanne ^a,c   Thoresen, Lars ^a   Ullman, Brett ^a   Lehmann, Juerg ^a   Calderon, Imelda ^a   Zhu, Xiuwen ^a   Gharbaoui, Tawfik ^a,d   Sengupta, Dipanjan ^a,d   Krishnan, Ashwin ^a   Gao, Yinghong ^a,e   Edwards, Jeff ^a,f   Barden, Jeremy ^a   Morgan, Michael ^a   Usmani, Khawja ^a   Chen, Chuan ^a   Sadeque, Abu ^a   Thatte, Jayant ^a,g   Solomon, Michelle ^a   Fu, Lixia ^a,h   Whelan, Kevin ^a   Liu, Ling ^a,i   Al Shamma, Hussien ^a   Gatlin, Joel ^a   Le, Minh ^a   Xing, Charles ^a   Espinola, Sheryll ^a,j   Jones, Robert M ^a   more..

^a ARENA PHARMACEUTICALS   (United States)

^b Focus Synthesis   (United States)

^c REGULUS THERAPEUTICS   (United States)

^d DART NEUROSCIENCE LLC   (United States)

^e EMD Millipore   (United States)

^f AMYLIN PHARMACEUTICALS INC   (United States)

^g GENERAL ATOMICS   (United States)

^h Synthetic Genomics Inc   (United States)

ⁱ PFIZER INC   (United States)

^j GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION   (United States)

more..

Author keywords

FTY720; Immunomodulators; S1P 1 agonist; Sphingosine 1 phosphate receptor

Indexed keywords

INDOLE DERIVATIVE; SPHINGOSINE 1 PHOSPHATE RECEPTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTOIMMUNE DISEASE; BRADYCARDIA; CONTROLLED STUDY; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG HALF LIFE; DRUG STRUCTURE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LYMPHOCYTE; MALE; NONHUMAN; RAT;

ANIMALS; AUTOIMMUNE DISEASES; DISEASE MODELS, ANIMAL; FEMALE; HUMANS; IMMUNOLOGIC FACTORS; INDOLES; LYMPHOCYTES; MALE; MICE; MICE, INBRED C57BL; MICROSOMES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, LYSOSPHINGOLIPID; STRUCTURE-ACTIVITY RELATIONSHIP;

ANIMALIA; RATTUS; RODENTIA;

EID: 84862195077     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2012.04.129     Document Type: Article

References (24)

1. K. Adachi, T. Kohara, N. Nakao, M. Arita, K. Chiba, T. Mishina, S. Sasaki, and T. Fujita Bioorg. Med. Chem. Lett. 5 1995 853
2. M. Kiuchi, K. Adachi, T. Kohara, M. Minoguchi, T. Hanano, Y. Aoki, T. Mishina, M. Arita, N. Nakao, M. Ohtsuki, Y. Hoshino, K. Teshima, K. Chiba, S. Sasaki, and T. Fujita J. Med. Chem. 43 2000 2946
3. J. Hale, L. Yan, W. Neway, R. Hajdu, J. Bergstrom, J. Milligan, G. Shei, G. Chrebet, R. Thornton, D. Card, M. Rosenbach, H. Rosen, and S. Mandala Bioorg. Med. Chem. Lett. 12 2004 4803
4. M. Oo, S. Thangada, M. Wu, C. Liu, T. Macdonald, K. Lynch, C. Lin, and T. Hla J. Biol. Chem. 282 2007 9082
5. L. Kappos, E. Radue, P. O'Conner, C. Polman, R. Hohlfeld, P. Calabresi, K. Salmaj, C. Agoropoulou, M. Layk, L. Auberson, and P. Burtin N. Eng. J. Med. 362 2010 387
6. J. Choi, S. Gardell, D. Herr, R. Rivera, C. Lee, K. Noguchi, S. Teo, Y. Yung, M. Lu, G. Kennedy, and J. Chun Proc. Natl. Acad. Sci. 108 2011 751
7. M. Hamada, M. Nakamura, M. Kiuchi, K. Marukawa, A. Tomatsu, K. Shimano, N. Sato, K. Sugahara, M. Asayama, K. Takagi, and K. Adachi J. Med. Chem. 53 2010 3154
8. P. Gergely, E. Wallström, B. Nuesslein-Hildesheim, C. Bruns, F. Zécri, N. Cooke, M. Traebert, T. Tuntland, M. Rosenberg, and M. Saltzman Multiple Sclerosis 15 2009 S125
9. http://www.receptos.com/clinical-development-RPC1063.php.
10. E. Demont, S. Arpino, R. Bit, C. Campbell, N. Deeks, S. Desai, S. Dowell, P. Gaskin, J. Gray, L. Harrison, A. Haynes, T. Heightman, D. Holmes, P. Humphreys, U. Kumar, M. Morse, G. Osborne, T. Panshal, K. Philpott, S. Taylor, R. Watson, R. Willis, and J. Witherington J. Med. Chem. 54 2011 6724
11. L. Piali, S. Froidevaux, P. Hess, O. Nayler, M. Bolli, C. Schlosser, B. Steiner, and M. Clozel J. Pharmacol. Exp. Ther. 337 2011 547
12. M. Bolli, S. Abele, C. Binkert, R. Bravo, S. Buchmann, D. Bur, J. Gatfield, P. Hess, C. Kohl, C. Mangold, B. Mathys, K. Menyhart, C. Müller, O. Nayler, M. Scherz, G. Schmidt, V. Sippel, B. Steiner, D. Strasser, A. Treiber, and T. Weller J. Med. Chem. 53 2010 4198
13. http://www.clinicaltrials.gov/ct2/show/NCT00852670?term= ACT-128800&rank=3.
14. http://clinicaltrials.gov/show/NCT01148810.
15. http://clinicaltrials.gov/show/NCT01375179.
16. J. Song, C. Matsuda, Y. Kai, T. Nishida, K. Nakajima, T. Mizushima, M. Kinoshita, T. Yasue, Y. Sawa, and T. Ito J. Pharmacol. Exp. Ther. 324 2008 276
17. Unpublished work.
18. S. Mattsson, M. Dahlströrm, and S. Karlsson Tetrahedron Lett. 48 2007 2497
19. http://www.discoverx.com/gpcrs/arrestin.php.
20. H. Kataoka, K. Sugahara, K. Shimano, K. Teshima, M. Koyama, A. Fukunari, and K. Chiba Cell. Mol. Immunol. 2 2005 439
21. S. Brode, T. Raine, P. Zaccone, and A. Cooke J. Immunol. 177 2006 6603
22. A. Bendele J. Musculoskelet. Neuron. Interact. 1 2001 377
23. M. Matsuura, T. Imayoshi, and T. Okumoto Int. J. Immunopharmacol. 22 2000 323
24. M. Forrest, S. Sun, R. Hajdu, J. Bergstrom, D. Card, G. Doherty, J. Hale, C. Keohane, C. Meyers, J. Milligan, S. Mills, N. Nomura, H. Rosen, M. Rosenbach, G. Shei, I. Singer, M. Tian, S. West, V. White, J. Xie, R. Proia, and S. Mandala J. Pharmacol. Exp. Ther. 309 2004 758