Optimization of amide-based EP3 receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 26, Issue 11, 2016, Pages 2670-2675

  Lee, Esther C Y ^a   Futatsugi, Kentaro ^a   Arcari, Joel T ^a   Bahnck, Kevin ^a   Coffey, Steven B ^a   Derksen, David R ^a   Kalgutkar, Amit S ^a   Loria, Paula M ^a   Sharma, Raman ^a  

^a PFIZER INC   (United States)

Author keywords

EP3 receptor; GPCR; Indazole; LipE; Metabolites; P gp; PGE2

Indexed keywords

AMIDE; PROSTAGLANDIN E RECEPTOR 3 ANTAGONIST; PROSTAGLANDIN RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG; PROSTAGLANDIN E RECEPTOR 3; PTGER3 PROTEIN, HUMAN;

AEROBIC METABOLISM; ARTICLE; DRUG SELECTIVITY; HUMAN; HUMAN CELL; IC50; IN VITRO STUDY; INTRINSIC CLEARANCE; IONIZATION; LIPOPHILICITY; METABOLIC STABILITY; REACTION OPTIMIZATION; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; SYNTHESIS;

AMIDES; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MOLECULAR STRUCTURE; RECEPTORS, PROSTAGLANDIN E, EP3 SUBTYPE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84963969024     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2016.04.009     Document Type: Article

References (18)

1. i) - cLog P (or Log D) P.D. Leeson, and B. Springthorpe Nat. Rev. Drug Disc. 6 2007 881
2. M.P. Edwards, and D.A. Price Annu. Rep. Med. Chem. 45 2010 380
3. Y. Sugimoto, and S. Narumiya J. Biol. Chem. 282 2007 11613
4. T.A. Samad, A. Sapirstein, and C.J. Woolf Trends Mol. Med. 8 2002 390
5. G.P. McCafferty, B.A. Misajet, N.J. Laping, R.M. Edwards, and K.S. Thorneloe Am. J. Physiol. Renal 295 2008 F507
6. M.E. Kimple, M.P. Keller, M.R. Rabaglia, R.L. Pasker, J.C. Neuman, N.A. Truchan, H.K. Brar, and A.D. Attie Diabetes 62 2013 1904
7. M.-A. Mawhin, P. Tilly, and J.-E. Fabre Prostaglandins Other Lipid Mediators 121 2015 4
8. P. Tilly, A.-L. Charles, S. Ludwig, F. Slimani, S. Gross, O. Meilhac, B. Geny, K. Stefansson, M.E. Gurney, and J.-E. Fabre Cardiovasc. Res. 101 2014 482
9. D. Flesch, D. Merk, C. Lamers, and M. Schubert-Zsilavecz Expert Opin. Ther. Pat. 23 2013 233
10. H. Juteau, Y. Gareau, M. Labelle, C.F. Sturino, N. Sawyer, N. Tremblay, S. Lamontagne, M.-C. Carrière, D. Denis, and K.M. Metters Bioorg. Med. Chem. Lett. 9 2001 1977
11. J. Singh, W. Zeller, N. Zhou, G. Hategen, R. Mishra, A. Polozov, P. Yu, E. Onua, J. Zhang, D. Zembower, A. Kiselyov, J.L. Ramírez, G. Sigthorsson, J.M. Bjornsson, M. Thorsteindottir, T. Andrésson, M. Bjarnadottir, O. Magnusson, J.-E. Fabre, K. Stefansson, and M.E. Gurney ACS Chem. Biol. 4 2009 115
12. J. Jin, A. Morales-Ramos, P. Eidam, J. Mecom, Y. Li, C. Brooks, M. Hilfiker, D. Zhang, N. Wang, D. Shi, P.-S. Tseng, K. Wheless, B. Budzik, K. Evans, J.-P. Jaworski, J. Jugus, L. Leon, C. Wu, M. Pullen, B. Karamshi, P. Rao, E. Ward, N. Laping, C. Evans, C. Leach, D. Holt, X. Su, D. Morrow, H. Fries, K. Thorneloe, and R. Edwards ACS Med. Chem. Lett. 1 2010 316
13. A.I. Morales-Ramos, Y.H. Li, M. Hilfiker, J.S. Mecom, P. Eidam, D. Shi, P.-S. Tseng, C. Brooks, D. Zhang, N. Wang, J.-P. Jaworski, D. Morrow, H. Fries, R. Edwards, and J. Jin Bioorg. Med. Chem. Lett. 21 2011 2806
14. M.A. Hilfiker, N. Wang, X. Hou, Z. Du, M.A. Pullen, M. Nord, R. Nagilla, H.E. Fries, C.W. Wu, A.C. Sulpizio, J.-P. Jaworski, D. Morrow, R.M. Edwards, and J. Jin Bioorg. Med. Chem. Lett. 19 2009 4292
15. M. Ungerer, and G. Münch Thromb. Haemost. 110 2013 868
16. M. Sanchez-Alavez, I. Klein, S.E. Brownell, I.V. Tabarean, C.N. Davis, B. Conti, and T. Bartfai PNAS 104 2007 3009
17. R.P. Ceddia, D. Lee, M.F. Maulis, B.A. Carboneau, D.W. Threadgill, G. Poffenberger, G. Milne, K.L. Boyd, A.C. Powers, O.P. McGuinness, M. Gannon, and R.M. Breyer Endocrinology 157 2016 220
18. S.A. Hitchcock J. Med. Chem. 55 2012 4877