Structure-activity relationships of (4-acylpyrrol-2-yl)alkanoic acids as inhibitors of the cytosolic phospholipase A2: Variation of the substituents in positions 1, 3, and 5

Journal of Medicinal Chemistry

Volumn 40, Issue 21, 1997, Pages 3381-3392

  Lehr, Matthias ^a  

^a UNIVERSITY OF MUNICH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

6 [2 (2 CARBOXYETHYL) 4 DODECANOYL 3,5 DIMETHYLPYRROL 1 YL]HEXANOIC ACID; 6 [2 (CARBOXYMETHYL) 4 DODECANOYL 3,5 DIMETHYLPYRROL 1 YL]NONANOIC ACID; ANTIASTHMATIC AGENT; ANTIINFLAMMATORY AGENT; ARACHIDONIC ACID; ARACHIDONYL TRIFLUOROMETHYL KETONE; PHOSPHOLIPASE A2; PHOSPHOLIPASE A2 INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CATTLE; CONTROLLED STUDY; CYTOSOL; DRUG POTENCY; DRUG SYNTHESIS; ENZYME INHIBITION; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION; THROMBOCYTE;

ANIMALS; ARACHIDONIC ACID; BLOOD PLATELETS; CALCIMYCIN; CATTLE; CYTOSOL; ENZYME INHIBITORS; FATTY ACIDS; HEXANOIC ACIDS; IONOPHORES; MOLECULAR STRUCTURE; PHOSPHOLIPASES A; PYRROLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0030770927     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970045j     Document Type: Article

References (34)

1. 2. J. Lipid Mediators Cell Signalling 1995, 12, 83-117.
2. 2 activities in stimulated platelets and their involvement in the arachidonic acid liberation. Br. J. Haematol. 1994, 88, 149-155.
3. Moncada, S.; Higgs, E. A. Metabolism of arachidonic acid. Ann. N.Y. Acad. Sci. 1988, 522, 454-463.
4. Samuelsson, B.; Dahlen, S. E.; Lindgren, J. A.; Rouzer, C. A.; Serhan, C. N. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 1991, 237, 1171-1176.
5. Weltzien, H. U. Cytolytic and membrane-perturbing properties of lysophosphatidylcholine. Biochim. Biophys. Acta 1979, 559, 259-287.
6. Venable, M. E.; Zimmerman, G. A.; McIntyre, T. M.; Prescott, S. M. Platelet-activating factor: a phospholipid autacoid with diverse actions. J. Lipid Res. 1993, 34, 691-702.
7. 2 inhibitors. Int. Arch. Allergy Immunol. 1995, 107, 432-434.
8. 2. Arch. Pharm. Pharm. Med. Chem. 1996, 329, 483-488.
9. 2 inhibitors. PCT Int. Appl. WO 88 06,885, 1988.
10. 2: Role and Function in Inflammation; Wong, P. Y. K., Dennis, E. A., Eds.; Plenum Press: New York, London, 1990; Vol. 275, pp 169-182.
11. 2. Agents Actions 1993, 38, 202-211.
12. 2. Biochemistry 1993, 32, 12560-12565.
13. 2: Variation of the alkanoic acid substituent, the acyl chain, and the position of the pyrrole nitrogen. Eur. J. Med. Chem., in press.
14. Sinisterra, J. V.; Mouloungui, Z.; Delmas, M.; Gaset, A. Barium hydroxide as catalyst in organic reactions; V. Application in the Horner reaction under solid-liquid phase-transfer conditions. Synthesis 1985, 1097-1100.
15. Nenitzescu, C. D.; Solomonica, E. Action of aliphatic diazo compounds on pyrrole and its homologs. Ber. Dtsch. Chem. Ges. 1931, 64, 1924-1931.
16. Massa, S.; Artico, M.; Corelli, F.; Mai, A.; Di Santo, R.; Cortes, S.; Marongiu, M. E.; Pani, A.; La Colla, P. Synthesis and antimicrobial and cytotoxic activities of pyrrole-containing analogs of trichostatin A. J. Med. Chem. 1990, 33, 2845-2849.
17. Hess, K.; Wissing, F. New transformations in the pyrrole series. Ber. Dtsch. Chem. Ges. 1914, 47, 1416-1428.
18. Loader, C. E.; Anderson, H. J. Pyrrole Chemistry - IX A new synthesis of 3-acylpyrroles from 4-acyl-2-pyrrolethiolcarboxylates using a catalytic decarbonylation reaction. Tetrahedron 1969, 25, 3879-3885.
19. Anderson, H. J.; Loader, C. E.; Foster, A. Pyrrole chemistry. XXII. A "one-pot" synthesis of some 4-acylpyrrole-2-carboxaldehydes from pyrrole. Can. J. Chem. 1980, 58, 2527-2530.
20. Jurch, G. R.; Tatum, J. H. Degradation of D-glucose with acetic acid and methyl-amine. Carbohydr. Res. 1970, 15, 233-239.
21. Ermili, A.; Castro, A. J.; Westfall, P. A. Products from attempted Vilsmeier-Haack acylations of pyrroles with selected amides. J. Org. Chem. 1965, 30, 339-343.
22. Treibs, A.; Michl, K. H. Substitution reactions of the pyrroles. IV. Addition of acrylic acid and its derivatives to pyrroles. Justus Liebigs Ann. Chem. 1954, 589, 163-173.
23. 2 inhibitors using bovine platelets and HPLC with UV-detection. Pharm. Pharmacol. Lett. 1992, 2, 176-179.
24. 2 by measuring phorbol ester-induced arachidonic acid release from bovine platelets with HPLC/UV-detection. Pharm. Pharmacol. Lett. 1995, 5, 108-111.
25. 2 activation, and histamine release in rat basophilic leukemia cells. Arch. Allergy Appl. Immunol. 1985, 78, 92-100.
26. 2. J. Biol Chem. 1994, 269, 19480-19487.
27. Visnjic, D.; Batinic, D.; Lasic, Z.; Knotek, M.; Marusic, M.; Banfic, H. Phorbol 12-myristate 13-acetate-mediated signalling in murine bone marrow cells. Biochem. J. 1995, 310, 163-170.
28. 2. Arch. Pharm. Pharm. Med. Chem. 1996, 329, 386-392.
29. 2. J. Lipid Mediators Cell Signalling 1995, 12, 119-130.
30. 2 is not required for arachidonic acid liberation during platelet activation. Eur. J. Biochem. 1993, 216, 169-175.
31. 2. Biochim. Biophys. Acta 1994, 1214, 88-96.
32. 2 inhibit release of free arachidonate in thrombin-stimulated human platelets. J. Biol. Chem. 1994, 269, 15625-15630.
33. 2. J. Med. Chem. 1997, 40, 2694-2705.
34. 2, on zymosan- and carrageenan-induced paw edema. Prostaglandins, Leukotrienes Essent. Fatty Acids 1996, 55 (Suppl. 1), 91.