Activation of the G-protein-coupled receptor 119: A conformation-base hypothesis for understanding agonist response

Journal of Medicinal Chemistry

Volumn 54, Issue 6, 2011, Pages 1948-1952

  McClure, Kim F ^a   Darout, Etzer ^a   Guimarães, Cristiano R W ^a   Deninno, Michael P ^a   Mascitti, Vincent ^a   Munchhof, Michael J ^a   Robinson, Ralph P ^a   Kohrt, Jeffrey ^a   Harris, Anthony R ^a   Moore, Dianna E ^a   Li, Bryan ^a   Samp, Lacey ^a   Lefker, Bruce A ^a   Futatsugi, Kentaro ^a   Kung, Daniel ^a   Bonin, Paul D ^a   Cornelius, Peter ^a   Wang, Ruduan ^a   Salter, Eben ^a   Hornby, Sam ^a   Kalgutkar, Amit S ^a   Chen, Yue ^a   more..

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBOXYLIC ACID DERIVATIVE; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR 119; ISOPROPYL 8 [5 METHYL 6 (2 METHYLPYRIDIN 3 YLOXY)PYRIMIDIN 4 YLOXY] 6 OXA 3 AZABICYCLO[3.2.1]OCTANE 3 CARBOXYLATE; ISOPROPYL 9 ANTI [[5 METHYL 6 [(2 METHYLPYRIDIN 3 YL)OXY]PYRIMIDIN 4 YL]OXY] 3 OXA 7 AZABICYCLO[3.3.1]NONANE 7 CARBOXYLATE; ISOPROPYL 9 SYN [[5 METHYL 6 [(2 METHYLPYRIDIN 3 YL)OXY]PYRIMIDIN 4 YL]OXY] 3 OXA 7 AZABICYCLO[3.3.1]NONANE 7 CARBOXYLATE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; DRUG ACTIVITY; DRUG CONFORMATION; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; NONHUMAN; RAT;

ANIMALS; AZABICYCLO COMPOUNDS; GLUCOSE TOLERANCE TEST; HUMANS; MOLECULAR CONFORMATION; PYRIMIDINES; RATS; RECEPTORS, G-PROTEIN-COUPLED; SPECIES SPECIFICITY; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79952779675     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm200003p     Document Type: Article

References (22)

1. Fyfe, M. C. T.; Overton, H. A.; Procter, M. J.; Reynet, C.; White, J. R. New nonpeptide-binding GPCRs as targets for diabetes and the metabolic syndrome Annu. Rep. Med. Chem. 2007, 42, 129-145
2. Overton, H. A.; Babbs, A. J.; Doel, S. M.; Fyfe, M. C. T.; Gardner, L. S.; Griffin, G.; Jackson, H. C.; Procter, M. J.; Rasamison, C. M.; Tang-Christensen, M.; Widdowson, P. S.; Williams, G. M.; Reynet, C. Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents Cell Metab. 2006, 3, 167-175
3. Chu, Z.-L.; Carroll, C.; Chen, R.; Alfonso, J.; Gutierrez, V.; He, H.; Lucman, A.; Xing, C.; Sebring, K.; Zhou, J.; Wagner, B.; Unett, D.; Jones, R. M.; Behan, D. P.; Leonard, J. N -Oleoyldopamine enhances glucose homeostasis through the activation of GPR119 Mol. Endocrinol. 2010, 24, 161-170
4. Ezzili, C.; Otrubova, K.; Boger, D. L. Fatty acid amide signaling molecules Biorg. Med. Chem. Lett. 2010, 20, 5959-5968
5. 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.-L.; Grottick, A. J.; Hauser, E. K.; Leonard, J.; Jones, R. M. Discovery of the first potent and orally efficacious agonist of the orphan G-protein coupled receptor 119 J. Med. Chem. 2008, 51, 5172-5175
6. Wu, Y.; Kuntz, J. D.; Carpenter, A. J.; Fang, J.; Sauls, H. R.; Gomez, D. J.; Ammala, C.; Xu, Y.; Hart, S.; Tadepalli, S. 2,5-Disubstituted pyridines as potent GPR119 agonists Bioorg. Med. Chem. Lett. 2010, 20, 2577-2581
7. Shah, U. GPR119 agonists: a promising new approach for the treatment of type 2 diabetes and related metabolic disorders Curr. Opin. Drug Discovery Dev. 2009, 12, 519-532
8. Fyfe, M. C.; McCormack, J. G.; Overton, H. A.; Procter, M. J.; Reynet, C. GPR119 agonists as potential new oral agents for the treatment of type 2 diabetes and obesity Expert Opin. Drug Discovery 2008, 3, 403-413 (Pubitemid 351618767)
9. 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. A role for intestinal endocrine cell-expressed G protein-coupled receptor 119 in glycemic control by enhancing glucagon-like peptide-1 and glucose-dependent insulinotropic peptide release Endocrinology 2008, 149, 2038-2047 (Pubitemid 351574507)
10. Jones, R. M.; Lehmann, J. Modulators of Metabolism and the Treatment of Disorders Related Thereto. WO 2007035355, 2007.
11. LMP2/6-311G* with solvent effects (water) included was used to calculate the difference in energy between axial and equatorial conformations. The energy maps were obtained using B3LYP 6-31G* in the gas phase.
12. Jones, R. M.; Leonard, J. N. The emergence of GPR119 agonists as anti-diabetic agents Annu. Rep. Med. Chem. 2009, 44, 149-170
13. Jones, R. M.; Leonard, J. N.; Buzard, D. J.; Lehmann, J. GPR119 agonists for the treatment of type 2 diabetes Expert Opin. Ther. Pat. 2009, 19, 1339-1359
14. During the course of this work the patent application (Xia, Y; Boyle, C. D.; GreenLee, W. J.; Chackalamannil, S.; Jayne, C. L.; Stamford, A. W.; Dai, X.; Harris, J. M.; Neustadt, B. R. Bicyclic Heterocycle Derivatives and Methods of use Thereof. WO2009055331, 2009,) appeared, disclosing related or identical structures.
15. See Supporting Information
16. To our knowledge this is the first primary literature disclosure of a GPR119 binding assay.
17. oct: a tool for lipophilicity determination in drug discovery. 2. Basic and neutral compounds J. Med. Chem. 2001, 44, 2490-2497 (Pubitemid 32852170)
18. 1A superagonists J. Med. Chem. 2010, 53, 7167-7179
19. Zimmerman, D. M.; Leander, J. D.; Cantrell, B. E.; Reel, J. K.; Snoddy, J.; Mendelsohn, L. G.; Johnson, B. G.; Mitch, C. H. Structure-activity relationships of trans -3,4-dimethyl-4-(3-hydroxyphenyl)piperidine antagonists for.mu.- and.kappa.-opioid receptors J. Med. Chem. 1993, 36, 2833-2841 (Pubitemid 23315385)
20. Bissantz, C.; Bernard, P.; Hibert, M.; Rognan, D. Protein-based virtual screening of chemical databases. II. Are homology models of G-protein coupled receptors suitable targets- Proteins: Struct., Funct., Bioinf. 2003, 50, 5-25 (Pubitemid 36090604)
21. Darout, E.; Basak, A. The synthesis of azabicyclic heterocycles Tetrahedron Lett. 2010, 51, 2998-3001
22. Human accession number: NM-178471. Rat accession number: AR240217