Antiinflammatory phospholipase-A2 inhibitors. I

Abstract A novel series of dehydroabietylamine derivatives has been synthesized and shown to be inhibitors of phospholipase-A 2 (PLA 2 ). These compounds exhibit in vivo antiinflammatory activity in the rat carrageenan paw edema assay and support the concept of PLA 2 inhibition as an approach to the discovery of novel antiinflammatories.

[1]  F. Sun,et al.  Calcium stimulation of a novel lipoxygenase. , 1980, Biochemical and Biophysical Research Communications - BBRC.

[2]  S. Miller,et al.  Suppressive Mechanisms Involving Sensitization and Tolerance in Contact Allergy , 1980, Immunological reviews.

[3]  C. Leslie,et al.  A cytosolic phospholipase in human neutrophils that hydrolyzes arachidonoyl-containing phosphatidylcholine. , 1986, Biochimica et biophysica acta.

[4]  D. A. Spires,et al.  The mouse ear inflammatory response to topical arachidonic acid. , 1984, The Journal of investigative dermatology.

[5]  W G Hol,et al.  Structure of porcine pancreatic phospholipase A2 at 2.6 A resolution and comparison with bovine phospholipase A2. , 1983, Journal of molecular biology.

[6]  R. Dowling,et al.  Kinetics of phospholipase A2, arachidonic acid, and eicosanoid appearance in mouse zymosan peritonitis. , 1990, Journal of immunology.

[7]  B. Jakschik,et al.  Arachidonic acid metabolism in rat basophilic leukemia (RBL-1) cells☆ , 1978 .

[8]  R. Dorfman,et al.  THE RELATIVE THYMOLYTTC ACTIVITIES OF CORTICOIDS USING THE OVARIECTOMIZEDADRENALECTOMIZED MOUSE1 , 1961 .

[9]  R. Heinrikson,et al.  A new class of phospholipases A2 with lysine in place of aspartate 49. Functional consequences for calcium and substrate binding. , 1984, The Journal of biological chemistry.

[10]  F. Marks,et al.  Early prostaglandin E synthesis is an obligatory event in the induction of cell proliferation in mouse epidermis in vivo by the phorbol ester TPA. , 1980, Biochemical and biophysical research communications.

[11]  D. Wallach,et al.  Studies on the arachidonic acid cascade--I. Inhibition of phospholipase A2 in vitro and in vivo by several novel series of inhibitor compounds. , 1981, Biochemical pharmacology.

[12]  R. Heinrikson,et al.  The lysine-49 phospholipase A2 from the venom of Agkistrodon piscivorus piscivorus. Relation of structure and function to other phospholipases A2. , 1986, The Journal of biological chemistry.

[13]  H. Sprecher,et al.  Delta four acetylenic acids - selective inhibitors of the formation of slow reacting substance. , 1981, Biochemical and biophysical research communications.

[14]  R. Tukey,et al.  Mechanism of action of novel anti-inflammmatory drugs diflumidone and R-805. , 1977, Biochemical pharmacology.