Novel δ2-isoxazolines as group II phospholipase A 2 inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 14, 2004, Pages 3679-3681

  Basappa, ^a   Satish Kumar, M ^a   Nanjunda Swamy, S ^a   Mahendra, M ^a   Shashidhara Prasad, J ^a   Viswanath, B S ^a   Rangappa, K S ^a  

^a UNIVERSITY OF MYSORE   (India)

Author keywords

2 Isoxazoline; Aldoxime; Anti inflammatory; Phospholipase A2; Ursolic acid

Indexed keywords

2 BUTYL 5 CHLORO 3H IMIDAZOLYL 4 CARBALDEHYDE OXIME; 3 (2 BUTYL 5 CHLORO 3H IMIDAZOLYL 4 YL) 4,5 DIHYDROISOXAZOLE 5 CARBOXYLIC ACID ETHYL ESTER; 3 (2 BUTYL 5 CHLORO 3H IMIDAZOLYL 4 YL) 4,5 DIHYDROISOXAZOLE 5 CARBOXYLIC ACID METHYL ESTER; 3 (2 BUTYL 5 CHLORO 3H IMIDAZOLYL 4 YL) 4,5 DIHYDROISOXAZOLE 5 CARBOXYLIC ACID PHENYL ESTER; 3 (2 BUTYL 5 CHLORO 3H IMIDAZOLYL 4 YL) 4,5 DIHYDROISOXAZOLE CARBONITRILE; 3 (2 BUTYL 5 CHLORO 3H IMIDAZOLYL 4 YL) 5 PHENYL 4,5 DIHYDROISOXAZOLE; [3 (2 BUTYL 5 CHLORO 3H IMIDAZOLYL 4 YL) 4,5 DIHYDROISOXAZOLE] 5 ACETIC ACID METHYL ESTER; [3 (2 BUTYL 5 CHLORO 3H IMIDAZOLYL 4 YL) 4,5 DIHYDROISOXAZOLE]METHANOL; ANTIINFLAMMATORY AGENT; ISOXAZOLINE DERIVATIVE; OXIME DERIVATIVE; PHOSPHOLIPASE A2 INHIBITOR; SNAKE VENOM; UNCLASSIFIED DRUG; URSOLIC ACID; ALDEHYDE; ENZYME INHIBITOR; IMIDAZOLE DERIVATIVE; ISOXAZOLE DERIVATIVE; OXIME; PHOSPHOLIPASE A; TRITERPENE;

ANIMAL EXPERIMENT; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG ACTIVITY; DRUG SYNTHESIS; ENZYME INHIBITION; EXPERIMENTAL MOUSE; IN VIVO STUDY; MOUSE; NONHUMAN; SNAKE; STATISTICAL SIGNIFICANCE; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; COMPARATIVE STUDY; DRUG ANTAGONISM; ENZYMOLOGY; METABOLISM;

SERPENTES;

ALDEHYDES; ANIMALS; ANTI-INFLAMMATORY AGENTS; ENZYME INHIBITORS; IMIDAZOLES; ISOXAZOLES; MICE; MODELS, MOLECULAR; OXIMES; PHOSPHOLIPASES A; SNAKE VENOMS; STRUCTURE-ACTIVITY RELATIONSHIP; TRITERPENES;

EID: 2942625965     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.05.012     Document Type: Article

References (22)

1. Fox N., Song M., Schermenti J., Sharp J.D., White D.L., Snyder D.W., Hartley L.W., Carlson D.G., Bach N.J., Dillard R.D., Draheim S.E., Bobbit J.L., Fisher L., Mihelich E.D. Eur. J. Pharmacol. 308:1996;195
2. Glaser K.B. Adv. Pharmacol. 32:1995;31
3. Mayer R.J., Marshall L.A. FASEB J. 7:1993;339
4. Vishwanath B.S., Fawzy A.A., Franson R.C. Inflammation. 12:1988;549
5. Sekar K., Mala S.V., Yogavel M., Velmurugan D., Ming-Jye P., Viswanath B.S., Gowda T.V., Jeyaprakash A.A., Tsai M.-D. J. Mol. Biol. 333:2003;367
6. 2 enzymes. In: Structure, Function and Mechanism; John Wiley and Sons: England, 1997
7. Fujii S., Tahara Y., Toyomoto M. Biochem. J. 7(308):1995;297
8. Amgad G., Habeeb, Praveen Rao P.N., Edward E.K. J. Med. Chem. 44:2001;2921
9. Ravikumar K.R., Mallesha H., Basappa, Rangappa K.S. Eur. J. Med. Chem. 38:2003;163
10. Ravikumar K.R., Mallesha H., Rangappa K.S. Arch. Pharm. 336:2003;159
11. Beeranahally Doreswamy H., Basappa, Madegowda M., Mantelingu K., Sridhar Anandalwar M., Javaregowda Prasad S., Rangappa K.S. Anal. Sci. 2003;31-32
12. Basappa, Sadashiva M.P., Mantelingu K., Nanjunda Swamy S., Rangappa K.S. Bioorg. Med. Chem. 11:2003;4539
13. Caramella P., Grunanger P. Padwa A. 1, 3-Dipolar Cycloaddition Chemistry. Vol. 1:1984;337 John Wiley and Sons, New York
14. Huisgen R. Angew. Chem., Int. Ed. Engl. 2:1963;565
15. 17
16. 14C] oleic acid was mixed with scintillation cocktail 13 and counted in a Hewlett Packard liquid Scintillation Analyzer TRI CARB 2100 TR
17. Vishwanath B.S., Frey F.J., Bradbury M.J., Dallman M.F., Frey B.M. J. Clin. Invest. 92:1993;1974
18. 2 -isoxazolines in 20 μL saline. The left footpads received 20 μL of saline, which served as control. After 45 min, mice were sacrificed by cervical dislocation and both legs were cut at the ankle joint and weighed individually. The increase in weight due to edema was calculated as the edema ratio, which equals the weight of edematous leg × 100/weight of the normal leg minimum edema dose, is defined as the microgram of protein causing an edema ration of 120%. Edema ratio=weight of edematous leg × 100/weight of normal leg
19. Otwinowski Z., Minor W. Processing of X-ray Diffraction Data Collected in Oscillation mode. Carter C.W. Jr., Sweet R.M. Methods in Enzymology, Macromolecular Crystallography. Vol. 276:1997;307 Academic, Dallas, TX
20. Sheldrick, G.M. SHELX-97; University of Göttingen, Göttingen, Germany, 1997
21. Johnson, C.K. ORTEP-II. A Fortran Thermal-Ellipsoid Plot Program. Report ORNL-5138; Oak Ridge National Laboratory, Oak Ridge, TN, USA, 1976
22. Crystallographic data (excluding structure factors) for the structures have been deposited with the Cambridge Crystallographic center as supplementary publication numbers CCDC No 235618 for compound 2. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union road, Cambridge, CB2 IEZ, UK (fax: +44(0) 1223336033 or e-mail: deposit@ccdc.cam.ac.uk)