Although various nonsteroidal anti-inflammatory drugs have already been put on the market, they are all unsatisfactory in respect of efficacy, so that the development of an anti-inflammatory drug from new standpoints has been eagerly expected.
It has already been known that the inhibition of production of prostaglandins (PGs) brings about an anti-inflammatory effect. Meanwhile, many studies have recently been made on leukotrienes (LTs) to make their physiological activities apparent. That is, LTB.sub.4 exhibits an activity of highly activating the migration of leukocyte to cause the excess accumulation thereof, thus contributing to the acceleration of inflammatory reactions, while LTC.sub.4 and D.sub.4 have been ascertained to exhibit an effect of enhancing the permeability of a blood vessel. Accordingly, it is conceivable that a more excellent anti-inflammatory drug can be developed if the inhibitory activity against LTs production is combined with that against PGs production at a well-balanced activity ratio. Further, such an anti-inflammatory drug may be effectively applied to asthma, inflammatory dermatitis, inflammatory enteric diseases, arthritis and so on by virtue of its pathological effects.
No drug has been developed as yet from the standpoint described above.
Under these circumstances, the inventors of the present invention have eagerly studied for many years and have found that a naphthalene derivative which will be described below acts as an excellent anti-inflammatory drug. The present invention has been accomplished on the basis of this finding.
With respect to naphthalene derivatives, for example, Japanese Patent Laid-Open No. 263943/1986 discloses naphthalene derivatives exhibiting an inhibitory activity against 5-lipoxygenase, while Aust. J. Chem., U, 2241 (1977) discloses those substituted with an alkenylcarboxylic acid group at the 1-position. However, not only these derivatives are distinguishable from those of the present invention in respect of chemical structure, but also these documents are silent on the efficacy thereof as a drug.
USPTO Backgrounds
USPTO Backgrounds