Discovery of diphenyloxazole and Nδ-Z-ornithine derivatives as highly potent and selective human prostaglandin EP4 receptor antagonists

Journal of Medicinal Chemistry

Volumn 48, Issue 9, 2005, Pages 3103-3106

  Hattori, Kouji ^a   Tanaka, Akira ^a   Fujii, Naoaki ^a   Takasugi, Hisashi ^a   Tenda, Yoshiyuki ^b   Tomita, Masayuki ^a   Nakazato, Shoko ^a   Nakano, Keiko ^a   Kato, Yasuko ^a   Kono, Yutaka ^a   Murai, Hidetsugu ^c   Sakane, Kazuo ^a  

^a Med Chemistry Research Laboratories   (Japan)

^b Drug Discovery Laboratories P   (Japan)

^c ASTELLAS PHARMA INC   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

7 [3 [(4 PHENYLSEMICARBAZIDO)METHYL] 7 OXABICYCLO[2.2.1]HEPT 2 YL] 5 HEPTENOIC ACID; BENZENE DERIVATIVE; DIPHENYLOXAZOLE DERIVATIVE; ILOPROST; IMMUNOGLOBULIN E; INTERLEUKIN 4; LIPOPOLYSACCHARIDE; N DELTA ORNITHINE DERIVATIVE; ORNITHINE DERIVATIVE; OXAZOLE DERIVATIVE; PROSTAGLANDIN D2; PROSTAGLANDIN DERIVATIVE; PROSTAGLANDIN E; PROSTAGLANDIN E RECEPTOR; PROSTAGLANDIN E2; PROSTAGLANDIN E4 RECEPTOR ANTAGONIST; PROSTAGLANDIN F2; PROSTANOID RECEPTOR; RECEPTOR SUBTYPE; UNCLASSIFIED DRUG; DRUG DERIVATIVE; EP4 RECEPTOR; IMMUNOLOGICAL ADJUVANT; ORNITHINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANTIGEN PRESENTING CELL; ARTICLE; CELL DIFFERENTIATION; CELLULAR IMMUNITY; DOG; DRUG ANTAGONISM; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG HALF LIFE; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; IMMUNE RESPONSE; KNOCKOUT GENE; MOLECULAR CLONING; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; ANIMAL; B LYMPHOCYTE; BIOSYNTHESIS; DRUG EFFECT; HUMAN; IN VITRO STUDY; METABOLISM; RADIOASSAY; STEREOISOMERISM; SYNTHESIS;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; B-LYMPHOCYTES; DINOPROSTONE; DOGS; HUMANS; IMMUNOGLOBULIN E; ORNITHINE; OXAZOLES; RADIOLIGAND ASSAY; RATS; RECEPTORS, PROSTAGLANDIN E; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 20944449218     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050085k     Document Type: Article

References (24)

1. 4 prostanoid receptor signaling. Life Sci. 2003, 74, 143-153. Benoit, P.; De Leval, X.; Pirotte, B.; Dogne, J.-M. Latest discoveries in prostaglandin receptor modulators. Expert Opin. 2002, 12, 1225-1235. DeLong, M. Prostaglandin receptor ligands: Recent patent activity. IDrugs 2000, 3, 1039-1052.
2. 4 prostanoid receptor signaling. Life Sci. 2003, 74, 143-153. Benoit, P.; De Leval, X.; Pirotte, B.; Dogne, J.-M. Latest discoveries in prostaglandin receptor modulators. Expert Opin. 2002, 12, 1225-1235. DeLong, M. Prostaglandin receptor ligands: Recent patent activity. IDrugs 2000, 3, 1039-1052.
3. 4 prostanoid receptor signaling. Life Sci. 2003, 74, 143-153. Benoit, P.; De Leval, X.; Pirotte, B.; Dogne, J.-M. Latest discoveries in prostaglandin receptor modulators. Expert Opin. 2002, 12, 1225-1235. DeLong, M. Prostaglandin receptor ligands: Recent patent activity. IDrugs 2000, 3, 1039-1052.
4. Abramovitz, A. M.; Adam, M.; Boie, Y. The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim. Biophys. Acta 2000, 1483, 285-293. Negishi, M.; Sugimoto, Y.; Ichikawa, A. Molecular mechanisms of diverse action of prostanoid receptors Biochim. Biophys. Acta 1995, 1259, 109-120.
5. Abramovitz, A. M.; Adam, M.; Boie, Y. The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim. Biophys. Acta 2000, 1483, 285-293. Negishi, M.; Sugimoto, Y.; Ichikawa, A. Molecular mechanisms of diverse action of prostanoid receptors Biochim. Biophys. Acta 1995, 1259, 109-120.
6. Coleman, R. A.; Smith, W. L.; Narumiya, S. International union of pharmacology classification of prostanoid receptors, distribution and structure of the receptors and their subtypes. Pharmacol. Rev. 1994, 46, 205-229.
7. 4 receptors expressed with semliki forest virus. Br. J. Pharamcol. 1997, 121, 1673-1678.
8. 4 receptors expressed with semliki forest virus. Br. J. Pharamcol. 1997, 121, 1673-1678.
9. 4 receptors expressed with semliki forest virus. Br. J. Pharamcol. 1997, 121, 1673-1678.
10. 4 subtypes regulate activation and differentiation of mouse B lymphocytes to IgE-secreting cells. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 10978-10983.
11. 2 that regulate cellular immune responses in the mouse. J. Clin. Invest. 2001, 108, 1229-1235.
12. 2 receptors in the pathogenesis of rheumatoid arthritis. J. Clin. Invest. 2002, 110, 651-658.
13. 4 in colon carcinogenesis. Cancer Res. 2002, 62, 28-32.
14. 2. Mol. Pharamacol. 2001, 60, 36-41.
15. i) for ligands in the previously reported method; see in refs 2 and 4.
16. Hattori, K.; Tabuchi, S.; Okitsu, O.; Taniguchi, K. A simple stereoselective synthesis and biological evaluation of FR-181157: orally active prostacyclin mimetic. Bioorg. Med. Chem. Lett. 2003, 13, 4277-4279.
17. 1 prostanoid receptor. Bioorg. Med. Chem. Lett. 1999, 9, 2699-2704. Yee, Y. K.; Bernstein, P. R.; Adams, E. J.; Brown, F. J.; Cronk, L. A.; Hebbel, K. C.; Vacek, E. P.; Krell, R. D.; Snyder, D. W. A new series of selective leukotriene antagonists: exploration and optimization of the acidic region in 1,6-disubstituted indoles and indazoles. J. Med. Chem. 1990, 33, 2437-2451.
18. 1 prostanoid receptor. Bioorg. Med. Chem. Lett. 1999, 9, 2699-2704. Yee, Y. K.; Bernstein, P. R.; Adams, E. J.; Brown, F. J.; Cronk, L. A.; Hebbel, K. C.; Vacek, E. P.; Krell, R. D.; Snyder, D. W. A new series of selective leukotriene antagonists: exploration and optimization of the acidic region in 1,6-disubstituted indoles and indazoles. J. Med. Chem. 1990, 33, 2437-2451.
19. 1 prostanoid receptor. Bioorg. Med. Chem. Lett. 1999, 9, 2699-2704. Yee, Y. K.; Bernstein, P. R.; Adams, E. J.; Brown, F. J.; Cronk, L. A.; Hebbel, K. C.; Vacek, E. P.; Krell, R. D.; Snyder, D. W. A new series of selective leukotriene antagonists: exploration and optimization of the acidic region in 1,6-disubstituted indoles and indazoles. J. Med. Chem. 1990, 33, 2437-2451.
20. Measurements of the concentration of 1, 3, and 8 in plasma were measured using HPLC or LC/MS.
21. 2 promotes IL-4-induced IgE and IgG1 synthesis. J. Immunol. 1990, 145, 2644-2651.
22. 2 promotes IL-4-induced IgE and IgG1 synthesis. J. Immunol. 1990, 145, 2644-2651.
23. Assay was performed by the previously described method in refs 14 and 16.
24. Fedric, E. R.; Phipps, R. P. Reactive oxygen species and not lipoxygenase products are required for mouse B-lymphocyte activation and differentiation. Int. J. Immunopharmacol. 1994, 16, 533-546.