Design and synthesis of 1-indol-1-yl-propan-2-ones as inhibitors of human cytosolic phospholipase A2α

Journal of Medicinal Chemistry

Volumn 49, Issue 8, 2006, Pages 2611-2620

  Ludwig, Joachim ^a   Bovens, Stefanie ^a   Brauch, Carsten ^a   Elfringhoff, Alwine Schulze ^a   Lehr, Matthias ^a  

^a UNIVERSITY OF MÜNSTER   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

1 [3 (4 DECYLOXYPHENOXY) 2 OXOPROPYL]INDOLE 3,5 DICARBOXYLATE; 1 INDOL 1 YL PROPAN 2 ONE DERIVATIVE; PHOSPHOLIPASE A2 INHIBITOR; PHOSPHOLIPASE A2ALPHA INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; ASSAY; CELL ASSAY; DRUG ACTIVITY; DRUG DESIGN; DRUG POTENCY; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; MEMBRANE VESICLE; STRUCTURE ACTIVITY RELATION; VESICLE ASSAY;

BLOOD PLATELETS; CYTOSOL; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HUMANS; INDOLES; KETONES; MOLECULAR STRUCTURE; PHOSPHOLIPASES A; PROPANE; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33646146486     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm051243a     Document Type: Article

References (35)

1. Serhan, C. N.; Haeggström, J. Z.; Leslie, C. C. Lipid mediator networks in cell signaling: update and impact of cytokines. FASEB J. 1996, 10, 1147-1158.
2. Huang, Y. H.; Schafer-Elinder, L.; Wu, R.; Claesson, H. E.; Frostegard, J. Lysophosphatidylcholine (LPC) induces proinflammatory cytokines by a platelet-activating factor (PAF) receptor-dependent mechanism. Clin. Exp. Immunol 1999, 116, 326-331.
3. Ryborg, A. K.; Deleuran, B.; Sogaard, H. R.; Kragballe, K. Intracutaneous injection of lysophosphatidylcholine induces skin inflammation and accumulation of leukocytes. Acta Derm. Venereol. 2000, 80, 242-246.
4. 2. Expert Opin. Ther. Pat. 1993, 3, 1141-1155.
5. 2. Expert Opin. Ther. Pat. 1995, 5, 673-683.
6. 2 inhibitors in development. Expert Opin. Invest. Drugs 1997, 6, 279-298.
7. 2 inhibitors. Emerging Drugs 1998, 3, 333-344.
8. 2 inhibitors in inflammation. Expert Opin. Ther. Pat. 2001, 11, 1123-1136.
9. 2 inhibitors. Expert Opin. Ther. Pat. 2004, 14, 937-950.
10. 2 enzymes: classification and characterization. Biochim. Biophys. Acta 2000, 1488, 1-19.
11. 2 enzymes. Prostaglandins Other Lipid Mediators 2002, 65-69, 3-58.
12. 2 is coupled to hormonally regulated release of arachidonic acid. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 6147-6151.
13. 2 in allergic response and parturition. Nature 1997, 390, 618-622.
14. 2. Nature 1997, 590, 622-625.
15. 2 regulation. J. Biol. Chem. 2000, 275, 20146-20156.
16. 2α- deficient mice are resistant to collagen-induced arthritis. J. Exp. Med. 2003, 197, 1297-1302.
17. 2-mediated bone resorption associated with inflammation. J. Exp. Med. 2003, 197, 1303-1310.
18. 2α reigns supreme in arthritis and bone resorption. Trends Immunol. 2004, 25, 116-119.
19. 2. PCT Int. Appl. WO2003048122, 2003.
20. Khurdayan, V.; Cullell-Young, M. Cronicles in drug discovery. Drug News & Perspect. 2005, 18, 227-280.
21. 2. J. Med. Chem. 2000, 43, 1041.
22. 2 based on a 1,3-disubstituted propan-2-one skeleton. J. Med. Chem. 2002, 45, 1348-1362.
23. 2. J. Med. Chem. 1997, 40, 2694-2705.
24. 2-mediated arachidonic acid release by several indole-2-carboxylic acids and 3-(pyrrol-2-yl)propionic acids in bovine and in human platelets. Arch. Pharm. (Weinheim, Ger.) 2000, 333, 312-314.
25. 2α-mediated arachidonic acid release in intact platelets: variation of the keto moiety. J. Enzyme Inhib. Med. Chem. 2005, 20, 429-437.
26. Wiesner, I.; Kolinsky, J.; Bruthans, V.; Sieber, J. Glycidyl ethers of monovalent phenols. CS 107473, 1963 CA: 60: 30832.
27. Ludwig, J.; Lehr, M. Convenient synthesis of pyrrole- and indole-carboxylic acid tert-butylesters. Synth. Commun. 2004, 34, 3691-3695.
28. Gwaltney, S. L.; Jae, H.-S.; Kalvin, D. M.; Liu, G.; Sham, H. L.; Li, Q.; Claiborne, A. K.; Wang, L.; Barr, K. J.; Woods, K. W. Substituted oxazolines as antiproliferative agents. PCT Int. Appl. WO0006556, 2000.
29. 2. J. Pharm. Biomed. Anal. 2004, 35, 135-142.
30. 2 is a 100-kDa protein in human monoblast U937 cells. J. Biol. Chem. 1991, 266, 5268-5272.
31. 2: structure-function studies with vesicle, micelle, and membrane assays. Biochim. Biophys. Acta 1999, 1420, 45-56.
32. Ware, J. A.; Saitoh, M.; Smith, M.; Johnson, P. C.; Salzmann, E. W. Response of aequorin-loaded platelets to activators of protein kinase C. Am. J. Physiol. 1989, 256, C35-43.
33. 2 inhibitors, arachidonyltrifluoromethyl ketone, methyl arachidonylfluorophosphonate and palmityltrifluoromethyl ketone. Pharm. Pharmacol Commun. 1999, 5, 389-393.
34. 2α inhibitor with an activated keto group by rat liver microsomes. Abstract of the book, Annual Meeting of the German Pharmaceutical Society (DPhG), Mainz, Germany, 2005.
35. th Mainzer Forum Medicinal Chemistry: Mainz, Germany, 2002.