The metabolic routes, in which various compounds are biosynthesized from the same mother compound, i.e. arachidonic acid, are called "Arachidonate cascade" as a whole.
Arachidonic acid is metabolized by the action of lipoxygenase, e.g. 5-lipoxygenase, 12-lipoxygenase, and 15-lipoxygenase, to 5-hydroperoxyeicosatetraenoic acid (abbreviated as HPETE hereinafter), 12-HPETE and 15-HPETE, respectively.
These HPETEs are converted into 5-hydroxyeicosatetetraenoic acid (abbreviated as HETE hereinafter), 12-HETE and 15-HETE, respectively, by the action of peroxidase which convert a hydroperoxy group to a hydroxy group. Furthermore, LTA.sub.4 is also produced from 5-HPETE. LTA.sub.4 is converted into LTB.sub.4 and LTC.sub.4. LTC.sub.4 is converted into LTD.sub.4 by the action of .gamma.-glutamyl transpeptidase. Moreover, it has been defined that LTD.sub.4 is metabolized to LTE.sub.4 (see Biochem. Biophys. Res. Commun., 91, 1266 (1979) and Prostaglandins, 19 (5), 645 (1980)).
Moreover, the action of LTB.sub.4 has been gradually identified recently. Namely, it as been identified that LTB.sub.4 having the following structure: ##STR12## (wherein the double bonds between 6th- and 7th- carbon, 8th- and 9th-carbon, 10th- and 11th- carbon and 14th- and 15th-carbon, are Z, E, E and Z, respectively), possesses a powerful action of polymorphonuclear leukocytes (PMNLs) accumulation and PMNLs adhesion, and PMNLs degranulation (see Nature, 286, 264 (1980), Proc. Nat. Acad. Sci. U.S.A. 78, 3887 (1981) and J. Biol. Chem., 256, 5317 (1981)). Moreover it has been considered that LTB.sub.4 promotes the release of arachidonic metabilites by attacking various cells as it has the powerful action like calcium ionophore (see J. Biol. Chem., 257, 4746 (1982)).
Moreover, LTB.sub.4 in high concentration has been detected at the sites of various inflammation, for example, rheumatism, spinal arthritis (see Klichstein L. B., Shapleigh, C. and Goetzl, E. J. (1980) J. Clin. Invest., 66, 1166-1170), gout (Rae, S. A., Davidson, E. M. and Smith, M. J. H. (1982) Lancet II 1122-1123), psoriasis (see Grabbe, J., Czarnetzki, B. M., Rosenbach, T. and Mardin, M. (1984) J. Invest. Dermatol., 82, 477-479), ulceractive colitis (see Sharon, P. and Stenson, W. F. (1984) Gastroenterology 86, 453-460), respiratory disease (see O'Driscoll, B. R., Cromwell, O. and Kay, A. B. (1984) Clin. Exp., Immunol., 55, 397-404). The fact described above shows that LTB.sub.4 is deeply related to various inflammation.
Accordingly, the antagonistic agents on LTB.sub.4 are considered to be useful as anti-inflammatory agents and antiallergic agents.