Inhibition of group IVA cytosolic phospholipase A2 by novel 2-oxoamides in vitro, in cells, and in vivo

Journal of Medicinal Chemistry

Volumn 47, Issue 14, 2004, Pages 3615-3628

  Kokotos, George ^a   Six, David A ^b   Loukas, Vassilios ^a   Smith, Timothy ^b   Constantinou Kokotou, Violetta ^c   Hadjipavlou Litina, Dimitra ^d   Kotsovolou, Stavroula ^a   Chiou, Antonia ^a   Beltzner, Christopher C ^b   Dennis, Edward A ^b  

^a UNIVERSITY OF ATHENS   (Greece)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c AGRICULTURAL UNIVERSITY OF ATHENS   (Greece)

^d ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

Author keywords

[No Author keywords available]

Indexed keywords

2 OXOAMIDE DERIVATIVE; 3 [1 (2 OXOPENTADECANOYL)PYRROLIDIN 2 YL]PROPIONIC ACID; 3 [2 (2 OXODODECANOYL)PYRROLIDIN 2 YL]PROPIONIC ACID; 4 (HEXADECANOYLAMINO)BUTYRIC ACID; 4 [(2 OXODODECANOYL)AMINO]OCTANOIC ACID; 4 [(2 OXOHEXADECANOYL)AMINO]BUTANOIC ACID; 4 [(2 OXOOCTANOYL)AMINO] 5 PHENYLPENTANOIC ACID; 4 [(2 OXOOCTANOYL)AMINO]BUTANOIC ACID; 4 [(2 OXOPENTADECANOYL)AMINO] 5 PHENYLPENTANOIC ACID; 4 [(2 OXOPENTADECANOYL)AMINO]PENTANOIC ACID; 4 [(2 OXOPENTANODECANOYL)AMINO]OCTANOIC ACID; 4 AMINOBUTYRIC ACID; 5 (DECYLOXY) 4 [(2 OXODODECANOYL)AMINO]PENTANOIC ACID; 6 METHYL 4 [(2 OXODODECANOYL)AMINO]HEPTANOIC ACID; 6 METHYL 4 [(2 OXOPENTADECANOYL)AMINO]HEPTANOIC ACID; ARACHIDONIC ACID; AX 001; AX 002; AX 003; AX 004; AX 005; AX 006; AX 007; AX 008; AX 009; AX 010; AX 011; AX 012; AX 013; AX 014; AX 015; AX 016; AX 017; AX 018; AX 019; AX 024; AX 026; AX 027; METHYL 4 [(2 OXOHEXADECANOYL)AMINO]BUTANOATE; NORLEUCINE; PHOSPHOLIPASE A2; PHOSPHOLIPASE A2 INHIBITOR; PROSTAGLANDIN E2; UNCLASSIFIED DRUG;

ANALGESIC ACTIVITY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CONTROLLED STUDY; CYTOSOL; DRUG POTENCY; DRUG SYNTHESIS; ENZYME INHIBITION; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

AMIDES; ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; BUTYRIC ACIDS; CELL LINE; EDEMA; HEPTANOIC ACIDS; MACROPHAGE ACTIVATION; MICE; OCTANOIC ACIDS; PAIN MEASUREMENT; PHOSPHOLIPASES A; RATS; RATS, INBRED F344; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 3042599028     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm030485c     Document Type: Article

References (45)

1. 2 enzymes: classification and characterization. Biochim. Biophys. Acta 2000, 1488, 1-19.
2. 2. Probing the role of histidine, aspartic acid, cysteine, and arginine. J. Biol. Chem. 1996, 271, 19225-19231.
3. 2 reveals a novel topology and catalytic mechanism. Cell 1999, 97, 349-360.
4. 2 and their effect on enzyme activity. J. Biol. Chem. 1998, 273, 207-214.
5. 2 by bromoenol lactone and trifluoromethyl ketones. J. Biol. Chem. 1995, 270, 445-450.
6. 2. J. Am. Chem. Soc. 1996, 118, 5519-5525.
7. 2 by methyl arachidonyl fluorophosphonate. Biochim. Biophys. Acta 1996, 1302, 55-60.
8. 2: structure-function studies with vesicle, micelle, and membrane assays. Biochim. Biophys. Acta 1999, 1420, 45-56.
9. 2. Nature 1997, 390, 622-625.
10. 2 are resistant to MPTP neurotoxicity. J. Neurochem. 1998, 71, 2634-2637.
11. 2 in allergic response and parturition. Nature 1997, 390, 618-622.
12. 2 is essential for both the immediate and the delayed phases of eicosanoid generation in mouse bone marrow-derived mast cells. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 4803-4807.
13. 2α as revealed by gene-targeted mice. Prostaglandins Other Lipid Mediators 2002, 68-69, 59-69.
14. 2. Nat. Immunol. 2000, 1, 42-46.
15. 2α is crucial for "on-time" embryo implantation that directs subsequent development. Development 2002, 129, 2879-2889.
16. 2 inhibitors. Nat. Immunol. 2000, 1, 13-15.
17. 2. J. Med. Chem. 2002, 45, 2891-2893.
18. 2. Biochemistry 1993, 32, 5935-5940.
19. 2. Biochemistry 1993, 32, 12560-12565.
20. 2. Biochemistry 1996, 35, 3712-3721.
21. 2. J. Am. Chem. Soc. 1996, 118, 5519-5525.
22. Removed in proofs.
23. 2: variation of the substitutents in positions 1, 3, and 5. J. Med. Chem. 1997, 40, 3381-3392.
24. 2. Bioorg. Med. Chem. Lett. 2001, 11, 2569-2572.
25. 2. J. Med. Chem. 2000, 43, 1041-1044.
26. 2. Part 2: Synthesis of potent and crystallized 4-triphenylmethylthio derivative "pyrrophenone". Bioorg. Med. Chem. Lett. 2001, 11, 587-590.
27. (a) Chiou, A.; Markidis, T.; Constantinou-Kokotou, V.; Verger, R.; Kokotos, G. Synthesis and study of a lipolytic α-keto amide inhibitor of pancreatic lipase. Org. Lett., 2000, 2, 347-350.
28. (b) Chiou, A.; Verger, R.; Kokotos, G. Synthetic routes and lipase-inhibiting activity of long-chain α-keto amides. Lipids 2001, 36, 535-542.
29. (a) Kokotos, G.; Verger, R.; Chiou, A. Synthesis of 2-oxo amide triacylglycerol analogues and study of their inhibition effect on pancreatic and gastric lipases. Chem.-Eur. J. 2000, 6, 4211-4217.
30. (b) Kotsovolou, S.; Chiou, A.; Verger, R.; Kokotos, G. Bis-2-oxo amide triacylglycerol analogues: a novel class of potent human gastric lipase inhibitors. J. Org. Chem. 2001, 66, 962-967.
31. 2 based on a 1,3-disubstituted propan-2-one skeleton. J. Med. Chem. 2002, 45, 1348-1362.
32. Sheehan, J. C.; Cruickshank, P. A.; Boshart, G. L. A convenient synthesis of water-soluble carbodiimides. J. Org. Chem. 1961, 26, 2525-2528.
33. (a) Leanna, M. R.; Sowin, T. J.; Morton, H. E. Synthesis of α-amino and α-alkoxy aldehydes via oxammonium oxidation. Tetrahedron Lett. 1992, 33, 5029-5032.
34. (b) Ma, Z.; Bobbitt, J. M. Organic oxoammonium salts: a new convenient method for the oxidation of alcohols to aldehydes and amines. J. Org. Chem. 1991, 56, 6110-6114.
35. Kokotos, G. A convenient one-pot conversion of N-protected amino acids and peptides into alcohols. Synthesis 1990, 299-301.
36. Kokotos, G.; Noula, C. Selective one-pot conversion of carboxylic acids into alcohols. J. Org. Chem. 1996, 61, 6994-6996.
37. 2 binds with high affinity and specificity to phosphatidylinositol 4,5-bisphosphate resulting in dramatic increases in activity. J. Biol. Chem. 1998, 273, 2184-2191.
38. 2 C2 domain for interfacial activity. J. Biol. Chem. 2003, 278, 23842-23850.
39. 2. J. Med. Chem. 1994, 37, 557-559.
40. 2 enzymes. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 11060-11064.
41. 2s. J. Biol. Chem. 1999, 274, 12263-12268.
42. 2 dependent induction of cyclooxygenase-2 in macrophages. J. Biol. Chem. 1999, 274, 25967-25970.
43. 1 macrophages. J. Biol. Chem. 1996, 271, 6758-6765.
44. Kontogiorgis, C.; Hadjipavlou-Litina, D. Biological evaluation of several coumarin derivatives designed as possible anti-inflammatory/antioxidant agents. J. Enzyme Inhib. Med. Chem. 2003, 18, 63-69.
45. Hadjipavlou-Litina, D.; Rekka, E.; Hadjipetrou-Kourounakis, L.; Kourounakis, P. N. Synthesis and biological studies of some novel anti-inflammatory aryl-hydroxy-amino-ketones. Eur. J. Med. Chem. 1991, 26, 85-90.