Discovery of a second generation agonist of the orphan G-protein coupled receptor GPR119 with an improved profile

Bioorganic and Medicinal Chemistry Letters

Volumn 22, Issue 4, 2012, Pages 1750-1755

  Semple, Graeme ^a   Lehmann, Juerg ^a   Wong, Amy ^a   Ren, Albert ^a   Bruce, Marc ^a   Shin, Young Jun ^a   Sage, Carleton R ^a   Morgan, Michael ^a   Chen, Wei Chao ^a   Sebring, Kristen ^a   Chu, Zhi Liang ^a   Leonard, James N ^a   Al Shamma, Hussein ^a   Grottick, Andrew J ^a   Du, Fuyong ^b   Liang, Yin ^b   Demarest, Keith ^b   Jones, Robert M ^a  

^a ARENA PHARMACEUTICALS   (United States)

^b JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

Diabetes; GPCR; GPR119; Lead optimization

Indexed keywords

APD 597; APD 668; AR 231453; AR 246881; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR 119 AGONIST; JNJ 28630355; JNJ 28630368; JNJ 38431055; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG MEGADOSE; DRUG METABOLISM; DRUG POTENCY; DRUG SOLUBILITY; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION;

EID: 84862778036     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.12.092     Document Type: Article

References (16)

1. Chu, Z.-L.; Jones, R. M.; He, H.; Carroll, C.; Gutierrez, V.; Lucman, A.; Moloney, M.; Gao, H.; Mondala, H.; Bagnol, D.; Unett, D.; Liang, Y.; Demarest, K.; Semple, G.; Behan, D. P.; Leonard, J. Endocrinology 2007, 148, 2601.
2. Chu, Z.-L.; Carroll, C.; Alfonso, J.; Gutierrez, V.; He, H.; Lucman, A.; Pedraza, M.; Mondala, H.; Gao, H.; Bagnol, D.; Chen, R.; Jones, R. M.; Behan, D. P.; Leonard, J. Endocrinology 2008, 149, 2038.
3. Semple, G.; Fioravanti, B.; Pereira, G.; Calderon, I.; Uy, J.; Choi, K.; Xiong, Y.; Ren, A.; Morgan, M.; Dave, V.; Thomsen, W.; Unett, D. J.; Xing, C.; Bossie, S.; Carroll, C.; Chu, Z.; Leonard, J.; Jones, R. M. J. Med. Chem. 2008, 51, 5172.
4. (a) Morgan, N. l. G.; Dhayal, S. Drug News Perspect. 2010, 23, 418
5. (b) Jones, R. M.; Leonard, J. N. Ann. Reports Med. Chem. 2009, 44, 149
6. (c) Shah, U. Curr. Opin. Drug Discov. Devel. 2009, 12, 519.
7. Semple, G.; Ren, A.; Fioravanti, B.; Pereira, G.; Calderon, I.; Choi, K.; Xiong, Y.; Sage, C. R.; Morgan, M.; Xing, C.; Chu, Z.-L.; Leonard, J. N.; Grottick, A. J.; Al-Shamma, H.; Jones, R. M. Bioorg. Med. Chem. Lett. 2011, 21, 3134.
8. (a) Jones, R.M. 239th ACS National Meeting, March 21-25, 2010, San Francisco, CA, (MEDI-316)
9. (b) Wong, A. S.; Lehmann, J.; Calderon, I.; Semple, G.; Xiong, Y.; Shin, Y-J.; Ren. A. S.; Choi, K. J. S.; Morgan, M.; Grottick, A. J.; Unett, D. J.; Chu, Z.; Leonard, J.; Jones, R. M. 241st ACS National Meeting, March 27-31 2011, Anaheim, CA. (MEDI 116).
10. (a) Full experimental details and compound characterization are described in the patent literature: Jones, R.M.; Lehmann, J. 2008 PCT Int. Appl., WO 2008005576.
11. (b) Jones, R.M.; Semple, G.; Xiong, Y.; Shin, Y.; Ren, A. S.; Lehmann, J.; Fioravanti, B.; Bruce, M. A.; Choi, K. 2005 PCT Int. Appl., WO 2005121121.
12. (c) Jones, R.M.; Semple, G.; Xiong, Y.; Shin, Y.; Ren, A. S. Calderon, I.; Choi, K.; Fioravanti, B.; Lehmann, J.; Bruce, M. A. 2005 PCT Int. Appl., WO 2005007647.
13. (a) Jones, R.M.; Lehmann, J. WO2007035355, 2007.
14. (b) Xia, Y.; Chackalamannil, S.; Greenlee, W. J.; Jayne, C.; Neustadt, B.; Stamford, A.; Vaccaro, H.; Xu, X. L.; Baker, H.; O'Neill, K.; Woods, M.; Hawes, B.; Kowalski, T. Bioorg. Med. Chem. Lett. 2011, 21, 3290
15. (c) McClure, K. F.; Darout, E.; Guimarães, C. R.; DeNinno, M. P.; Mascitti, V.; Munchhof, M. J.; Robinson, R. P.; Kohrt, J.; Harris, A. R.; Moore, D. E.; Li, B.; Samp, L.; Lefker, B. A.; Futatsugi, K.; Kung, D.; Bonin, P. D.; Cornelius, P.; Wang, R.; Salter, E.; Hornby, S.; Kalgutkar, A. S.; Chen, Y. J. Med. Chem. 2011, 54, 1948.
16. Effects of JNJ-38431055, a novel GPR119 receptor agonist, in randomized, double-blind, placebo-controlled studies in subjects with type 2 diabetes. Katz, L. B.; Gambale, J. J.; Rothenberg, P. L.; Vanapalli, S. R.; Vaccaro, N.; Xi, L.; Sarich, T. C.; Stein, P. P. Clin. Pharm. Ther. 2011, 90, 685.