Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP1 receptor antagonist for the treatment of inflammatory pain

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 9, 2009, Pages 2599-2603

  Hall, Adrian ^a   Billinton, Andy ^a   Brown, Susan H ^a   Chowdhury, Anita ^a   Clayton, Nicholas M ^a   Giblin, Gerard M P ^a   Gibson, Mairi ^a   Goldsmith, Paul A ^a   Hurst, David N ^a   Naylor, Alan ^a   Peet, Caroline F ^a   Scoccitti, Tiziana ^a   Wilson, Alexander W ^a   Winchester, Wendy ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

CNS penetration; EP1 antagonist; Inflammatory pain; Microdose; Pain

Indexed keywords

6 [2 [5 CHLORO 2 (2,4 DIFLUOROBENZYLOXY)PHENYL] 1 CYCLOPENTENYL] 2 PYRIDINECARBOXYLIC ACID; CARBOXYLIC ACID DERIVATIVE; G PROTEIN COUPLED RECEPTOR; GSK 269984A; GW 855454X; ROFECOXIB; SODIUM 6 [[5 CHLORO 2 [[(4 CHLORO 2 FLUOROPHENYL) METHYL]OXY]PHENYL]METHYL] 2 PYRIDINECARBOXYLATE; UNCLASSIFIED DRUG;

ANALGESIC ACTIVITY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CENTRAL NERVOUS SYSTEM; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG METABOLISM; DRUG PENETRATION; DRUG SENSITIVITY; DRUG STABILITY; DRUG STRUCTURE; FEMALE; HUMAN; HUMAN CELL; INFLAMMATION; MALE; MOUSE; NONHUMAN; PAIN; PLASMA CLEARANCE; RAT; RECEPTOR BLOCKING;

ANALGESICS; ANIMALS; CENTRAL NERVOUS SYSTEM; CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; HUMANS; HYDROGEN-ION CONCENTRATION; INFLAMMATION; INHIBITORY CONCENTRATION 50; MODELS, CHEMICAL; NICOTINIC ACIDS; PYRIDINES; RATS; RECEPTORS, PROSTAGLANDIN E; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 64249083593     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.02.112     Document Type: Article

References (45)

1. Kassuya C.A.L., Ferreira J., Claudino R.F., and Calixto J.B. Br. J. Pharmacol. 150 (2007) 727
2. Minami T., Uda R., Horiguchi S., Ito S., Hyodo M., and Hayashi M. Pain 57 (1994) 217
3. Fitzgerald G.A.C. Nat. Rev. Drug Disc. 2 (2003) 879
4. Huntjens D.R.H., Danhof M., and Della Pasqua O.E. Rheumatology 44 (2005) 846
5. Bianchi M., and Broggini M. Drugs 63 (2003) 37
6. Zhang Y., Shaffer A., Portanova J., Seibert K., and Isakson P.C. J. Pharmacol. Exp. Ther. 283 (1997) 1069
7. Trebino C.E., Stock J.L., Gibbons C.P., Naiman B.M., Wachtmann T.S., Umland J.P., Pandher K., Lapointe J.-M., Saha S., Roach M.L., Carter D., Thomas N.A., Durtschi B.A., McNeish J.D., Hambor J.E., Jakobsson P.-J., Carty T.J., Peez J.R., and Audoly L.P. Proc. Nat. Acad. Sci. 100 (2003) 9044
8. Kamei D., Yamakawa K., Takegoshi Y., Mikami-Nakanishi M., Nakatani Y., Oh-ishi S., Yasui H., Azuma Y., Hirasawa N., Ohuchi K., Kawaguchi H., Ishikawa Y., Ishii T., Uematsu S., Akira S., Murakami M., and Kudo I. J. Biol. Chem. 279 (2004) 33684
9. Xu D., Rowland S.E., Clark P., Giroux A., Côté B., Guiral S., Salem M., Ducharme Y., Friesen R.W., Méthot N., Mancini J., Audoly L., and Riendeau D. J. Pharm. Expt. Ther. 326 (2008) 754
10. Friesen R.W., and Mancini J.A. J. Med. Chem. 51 (2008) 1059
11. Coleman R.A., Smith W.L., and Narumiya S. Pharmacol. Rev. 46 (1994) 205
12. Narumiya S., Sugimoto Y., and Ushikubi F. Physiol. Rev. 79 (1999) 1193
13. Coleman R.A., Kennedy I., Humphrey P.P.A., Bunce K., and Lumley P. Comprehensive Medicinal Chemistry Vol. 3 (1990), Pergamon, Oxford, UK
14. Tober K.L., Wilgus T.A., Kusewitt D.F., Thomas-Ahner J.M., Maruyama T., and Oberyszyn T.M. J. Investig. Dermatol. 126 (2006) 205
15. Omote K., Kawamata T., Nakayama Y., Kawamata M., Hazama K., and Namiki A. Anesth. Analg. 92 (2001) 233
16. Kawahara H., Sakamoto A., Takeda A., Onodera H., Imaki J., and Ogawa R. Anesth. Analg. 93 (2001) 1012
17. Omote K., Yamamoto H., Kawamata T., Nakayama Y., and Namiki A. Anesth. Analg. 95 (2002) 1708
18. Minami T., Nakano H., Kobayashi T., Sugimoto Y., Ushikubi F., Ichikawa A., Narumiya S., and Ito S. Br. J. Pharmacol. 133 (2001) 438
19. Mebane H., Turnbach M.E., and Randich A. J. Pain 4 (2003) 392
20. Hall A., Billinton A., and Giblin G.M.P. Curr. Opin. Drug Disc. Dev. 10 (2007) 597
21. Sarkar S., Hobson A.R., Hughes A., Growcott J., Woolf C.J., Thompson D.G., and Aziz Q. Gastroenterology 124 (2003) '8
22. Lee T., Hedlund P., Newgreen D., and Andersson K.-E. J. Urol. 177 (2007) 1562
23. Schröder A., Newgreen D., and Andersson K.-E. J. Urol. 172 (2004) 1166
24. Kawano T., Anrather J., Zhou P., Park L., Wang G., Frys K.A., Kunz A., Cho S., Orio M., and Iadecola C. Nat. Med. 122 (2006) 225
25. Ahmad A.S., Saleem S., Ahmad M., and Doré S. Toxicol. Sci. 89 (2006) 265
26. Giblin G.M.P., Bit R.A., Brown S.H., Chaignot H.M., Chowdhury A., Chessell I.P., Clayton N.M., Coleman T., Hall A., Hammond B., Hurst D.N., Michel A.D., Naylor A., Novelli R., Scoccitti T., Spalding D., Tang S.P., Wilson A.W., and Wilson R. Bioorg. Med. Chem. Lett. 17 (2007) 385-389
27. Hall A., Brown S.H., Budd C., Clayton N.M., Giblin G.M.P., Goldsmith P., Hayhow T.G., Hurst D.N., Naylor A., Rawlings D.A., Scoccitti T., Wilson A.W., and Winchester W.J. Bioorg. Med. Chem. Lett. 19 (2009) 497
28. McKeown S.C., Hall A., Giblin G.M.P., Lorthioir O., Blunt R., Lewell X.Q., Wilson R.J., Brown S.H., Chowdhury A., Coleman T., Watson S.P., Chessell I.P., Pipe A., Clayton N., and Goldsmith P. Bioorg. Med. Chem. Lett. 16 (2006) 4767
29. Wilson A.W., Medhurst S.J., Dixon C.I., Bontoft N.C., Winyard L.A., Brackenborough K.T., De Alba J., Clarke C.J., Gunthorpe M.J., Hicks G.A., Bountra C., McQueen D.S., and Chessell I.P. Eur. J. Pain 10 (2006) 537
30. Mao B., Abrahim A., Ge Z., Ellison D.K., Hartman R., Prabu S.V., Reamer R.A., and Wyvratt J. J. Pharmaceut. Biomed. 28 (2002) 1101
31. Hartman R., Abrahim A., Clausen A., Mao B., Crocker L.S., and Ge Z. J. Liq. Chromatogr. R. T. 26 (2003) 2551
32. Knochel P., Yeh C.M.P., Berk S.C., and Talbert J. J. Org. Chem. 53 (1988) 2390
33. Knochel P., and Singer R.D. Chem. Rev. 93 (1993) 2117
34. Hall A., Bit R.A., Brown S.H., Chowdhury A., Giblin G.M.P., Hurst D.N., Kilford I.R., Lewell X., Naylor A., and Scoccitti T. Bioorg. Med. Chem. Lett. 18 (2008) 1592
35. Clarke S.E., and Jeffrey P. Xenobiotica 31 (2001) 591
36. 1 function. For further details see:. Schild H.O. Br. J. Pharmacol. Chemother. 4 (1949) 277
37. Arunlakshana O., and Schild H.O. Br. J. Pharmacol. Chemother. 14 (1959) 48
38. Crespi C.L., Miller V.P., and Penman B.W. Anal. Biochem. 248 (1997) 188
39. Hall A., Brown S.H., Chessell I.P., Chowdhury A., Clayton N.M., Coleman T., Giblin G.M.P., Hammond B., Healy M.P., Johnson M.R., Metcalf A., Michel A.D., Naylor A., Novelli R., Spalding D.J., Sweeting J., and Winyard L. Bioorg. Med. Chem. Lett. 17 (2007) 916
40. Keogh J.P., and Kunta J.R. Eur. J. Pharm. Sci. 27 (2006) 543
41. Tran T.T., Mital A., Gales T., Maleeff B., Aldinger T., Polli J.W., Aryton A., Ellens H., and Bentz J. J. Pharm. Sci. 93 (2004) 2108
42. Details of the full pharmacological profile and human pharmacokinetic data will be published elsewhere.
43. Knochel P., Dohle W., Gommermann N., Kniesel F.F., Kopp F., Korn T., Sapountzis I., and Vu V.A. Angew. Chem., Int. Ed. 42 (2003) 4302
44. Miyaura N., and Suzuki A. Chem. Rev. 95 (1995) 2457
45. Full experimental details and characterising data have been published, see: Giblin, G. M. P.; Hall, A.; Hurst, D. N.; Rawlings, D. A.; Scoccitti, T. PCT patent application WO2006066968A1, 2006.