Dicarboxylic acid inhibitors of phospholipase A2

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 7, 1997, Pages 793-798

  Springer, Dane M ^a   Luh, Bing Yu ^a   D'Andrea, Stan V ^a   Bronson, Joanne J ^a   Mansuri, Muzammil M ^a,c   Burke, James R ^b   Gregor, Kurt R ^b   Stanley, Paul L ^b   Tramposch, Kenneth M ^b  

^a BRISTOL MYERS SQUIBB   (United States)

^b BRISTOL MYERS SQUIBB PHARMACEUTICAL RESEARCH INSTITUTE   (United States)

^c GPC Biotech Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (3 CARBOXYPHENYL) 3 METHYL 5 (6,7,8,9 TETRAHYDRO 6,6,9,9 TETRAMETHYLPHENANTHREN 2 YL) 2,4 PENTADIENOIC ACID; 4 (3 CARBOXYPHENYL) 3,7 DIMETHYL 9 (2,6,6 TRIMETHYL 1 CYCLOHEXENYL) 2,4,6,8 NONATETRAENOIC ACID; ANTIINFLAMMATORY AGENT; ANTIPSORIASIS AGENT; PHOSPHOLIPASE A2; PHOSPHOLIPASE A2 INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG SYNTHESIS; EDEMA; ENZYME INHIBITION; HUMAN; HUMAN CELL; IN VITRO STUDY; MOUSE; NONHUMAN; NORMAL HUMAN; REACTION ANALYSIS; STEREOCHEMISTRY; THROMBOCYTE;

EID: 0030975348     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00110-8     Document Type: Article

References (34)

1. (a) Pruzanski, W.; Vadas, P. Immunology Today 1991, 12, 143.
2. (b) Hope, W. C.; Patel, B. J.; Fieldler-Nagy, C.; Wittreich, B. H. Inflammation 1990, 14, 543.
3. (c) Vishwanath, B. S.; Fawzy, A. A.; Franson, R. C. Inflammation 1988, 12, 549.
4. (d) Vadas, P.; Pruzanski, W. Laboratory Investigation 1986, 55, 391.
5. (e) Forster, S.; Ilderton, E.; Norris, J. F. B.; Summerly, R.; Yardley, H. J. Br. J. Derm. 1985, 112, 135.
6. (f) Pruzanski, W.; Vadas, P.; Stefanski, E. J. Rheumatol. 1985, 12, 211.
7. (g) Vadas, P.; Urowitz, M. B. J. Lab. Clin. Med. 1984, 104, 873.
8. (h) Franson, R.; Dobrow, R.; Weiss, J.; Elsbach, P.; Woglichi, W. B. J. Lipid Res. 1978, 19, 18.
9. (a) Clark, J. D.; Milona, N.; Knopf, J. L. Proc. Nat. Acad. Sci. U.S.A. 1990, 87, 7708.
10. (b) Kramer, R. M.; Roberts, E. F.; Manetta, J.; Putnam, J. E. J. Biol. Chem. 1991, 266, 5268.
11. (c) Clark, J. D.; Lin, L. L.; Kriz, R. W.; Ramesha, C. S.; Sultzman, L. A.; Lin, A. Y.; Milona, N.; Knopf, J. L. Cell 1991, 65, 1043.
12. (d) Sharp, J. D.; White, D. L.; Chiou, X. G.; Goodson, T.; Gamboa, G. C; McClure, D.; Burgett, S.; Hoskins, J.; Skatrud, P. L.; Sportsman, J. R.; Becker, G. W.; Kang, L. H.; Roberts, E. F.; Kramer, R. M. J. Biol. Chem. 1991, 266, 14850.
13. Nishijima, J.; Okamoto, M.; Ogawa, M.; Kosaki, G.; Yamano, T. J. Biochem. 1983, 94, 137.
14. (a) Hara, S.; Kudo, I.; Chang, H. W.; Matsuta, K.; Miyamoto, T.; Inoue, K. J. Biochem. 1989, 105, 395.
15. (b) Seilhamer, J. J.; Pruzanski, W.; Vadas, P.; Plant, S.; Miller, J. A.; Kloss, J.; Johnson, L. K. J. Biol. Chem. 1989, 264, 5335.
16. (c) Kramer, R. M.; Hession, C.; Johansen, B.; Hayes, G.; McGray, P.; Chow, E. P.; Tizard, R.; Pepinsky, R. B. J. Biol. Chem. 1989, 264, 5768.
17. (a) Musser, J. H.; Kreft, A. F.; Failli, A. A.; Demerson, C. A.; Shah, U. S.; Nelson, J. A. International Patent Publication 1991, WO91/06537; Chem. Abstr. 1991, 115, 135935.
18. (b) Failli, A. A.; Kreft, A. F.; Musser, J. H.; Banker, A. L.; Nelson, J. A.; Shah, U. S. US Patent 1991, 5,071,988; Chem. Abstr. 1992, 116, 151752.
19. (c) Djuric, S. W.; Haack, R. A.; Miyashiro, J. M. International Patent Publication 1992, WO92/21644; Chem. Abstr. 1993, 119, 8502.
20. (d) Tramposch, K. M.; Steiner, S. A.; Stanley, P. L.; Nettleton, D. O.; Franson, R. C.; Lewin, A. H.; Carroll, F. I. Biochem. Biophys. Res. Commun. 1992, 189, 272.
21. (e) Tramposch, K. M.; Chilton, F. H.; Stanley, P. L.; Franson, R. C.; Havens, M. B.; Nettleton, D. O.; Davern, L. D.; Darling, I. M.; Bonney, R. J. J. Pharmacol. Expt. Therapeut. 1994, 271, 852.
22. (f) Kohler, T.; Heinisch, M.; Kirchner, M.; Peinhardt, G.; Hirschelmann, R.; Nuhn, P. Biochemical Pharmacology 1992, 44, 805.
23. (g) LeMahieu, R. A.; Carson, M.; Han, R. J.; Madison, V. S.; Hope, W. C.; Chen, T.; Morgan, D. W.; Hendrickson, H. S. J. Med. Chem. 1993, 36, 3029.
24. (h) Beaton, H. G.; Bennion, C.; Connolly, S.; Cook, A. R.; Gensmantel, N. P.; Hallam, C.; Hardy, K.; Hitchin, B.; Jackson, C. G,; Robinson, D. H. J. Med. Chem. 1994, 37, 557.
25. (i) Carson, M.; Han, R. J.; LeMahieu, R. A.; Madison, V. S. US Patent 1994, 5,298,652; Chem. Abstr. 1994, 121, 231362.
26. 50 is therefore a measure of protection of the mouse ear from inflammation caused by the irritant. For the experimental details of this assay see ref 5d.
27. 50 of lonapalene (a known 5-lipoxegenase inhibitor and antipsoriasis agent) in this assay is 1000 μg/ear (for details see ref 5e).
28. 2 screen of proprietary compounds. Compounds 1, 4, 10, 12, and 17 were evaluated for binding and activation of retinoic acid receptors (RARs) α, β, γ. All the compounds tested failed to activate RARs α, β and γ.
29. 1H NMR spectrum of 4 obtained prior to chromatography was very clean for structure 4. There are only a few trace peaks in the baseline, and these could not be assigned unequivocally to another isomer. The yields reported for compound 4 and the other compounds shown in Table 1 (see ref 9) are unoptimized. The yields appear low due to losses from chromatography (yield for center cuts reported) and crystallization. We believe, however, that the actual yield of these reactions from starting aldehyde to product diacid is generally >80%.
30. 2/pentane); 17, 58%; 18, 45% (chromatographed using EtOAc/hexane).
31. 2 isolated from human synovial fluid (Marshall, L. A.; Bauer, J.; Sung, M. L.; Chang, J. Y. J. Rheumatol. 1991, 18, 59), and 3.2 μM against the same enzyme isolated from human polymorphonuclear leukocytes (Marki, F.; Breitenstein, W.; Beriger, E.; Bernasconi, R.; Caravatti, G.; Francis, J. E.; Paioni, R.; Wehrli, H. U.; Wiederkehr, R. Agents Actions 1993, 38, 202).
32. 2 isolated from human synovial fluid (Marshall, L. A.; Bauer, J.; Sung, M. L.; Chang, J. Y. J. Rheumatol. 1991, 18, 59), and 3.2 μM against the same enzyme isolated from human polymorphonuclear leukocytes (Marki, F.; Breitenstein, W.; Beriger, E.; Bernasconi, R.; Caravatti, G.; Francis, J. E.; Paioni, R.; Wehrli, H. U.; Wiederkehr, R. Agents Actions 1993, 38, 202).
33. 2 inhibitor see: Schevitz, R. W.; Bach, N. J.; Carlson, D. G.; Chirgadze, N. Y.; Clawson, D. K.; Dillard, R. D.; Draheim, S. E.; Hartley, L. W.; Jones, N. D.; Mihelich, E. D.; Olkowski, J. L.; Snyder, D. W.; Sommers, C.; Wery, J. P. Nature Struct. Biol. 1995, 2, 458.
34. 2 see ref 7.