Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1992-06-24
1994-06-07
Higel, Floyd D.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
544141, 548188, 548225, 548243, 5483231, 5483697, 548111, C07D20724, C07D23102, C07D26302, C07D27702, A61K 3140, A61K 3141
Patent
active
053190998
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to novel 3-benzylidene-1-carbamoyl-2-pyrrolidone analogues which have inhibitory activities against the production of leukotriene B.sub.4 (LTB.sub.4) and that of interleukin-1 (IL-1). In more detail, these derivatives are able to be applied to safe medicaments which show potent anti-inflammatory effects to acute and chronic inflammation and hardly cause stomach disease.
BACKGROUND OF THE INVENTION
Prior anti-inflammatory agents of non-steroid type are effective to the improvement in the early stages of rheumatism and acute inflammation, however, have some defects of being no effective to progressed rheumatic diseases such as osteonecrosis, the improvement in chronic rheumatic diseases, or the treatment of arthrosteitis etc., and of having potent activities to induce gastric ulcer caused by the inhibition of the production of prostaglandin E.sub.2 (PGE.sub.2).
Recently it has been revealed that leukotriene (LT), esp. LTB.sub.4 etc., which is a metabolite produced via the metabolism of arachidonic acid caused by 5-lipoxygenase, is an important mediator in inflammation reaction. Furthermore, it has been suggested that the cause of inflammation relates to IL-1 which is a kind of cytokines and that also chronic rheumatism is much influenced by cytokines such as IL-1.
In view of circumstances above, attentions have been paid to compounds having inhibitory activities against the production of LTB.sub.4 and IL-1, as a new type of anti-inflammatory agent. These compounds are much useful than known non-steroidal anti-inflammatories, in respect of that they are expected to have efficacy not only to acute inflammation but also to chronic inflammation, e.g., chronic arthrorheumatism etc.
With an intention to develop such anti-inflammatory agents as described above, a wide variety of compounds are disclosed in specifications of Kokai 58-79944, Kokai 61-257967, Kokai 62-42977, Kokai 1-305028, Kokai 2-4729, Kokai 2-256645, Kokai 2-270865, and Kokai 1-503782.
As stated above, it has been desired to develop anti-inflammatory agents capable of inhibiting the production of mediators relating to inflammation such as PGE.sub.2, LTB.sub.4, and IL-1, however, such an anti-inflammatory agent as being useful for treating chronic inflammation and having little side effect, e.g., stomach disease, has not been developed yet.
DISCLOSURE OF THE INVENTION
The present inventors have tried to find that the compounds of the formula (I): ##STR2## wherein R.sup.1 and R.sup.2 each is independently hydrogen, alkyl, alkoxy, or halogen; R.sup.3 is hydrogen or acyl; R.sup.4 is hydrogen, alkyl, hydroxy, alkoxy, cyano, or halogen; R.sup.5 and R.sup.6 each is independently hydrogen, alkyl, aryl, aralkyl, heterocyclic group, substituted or unsubstituted amino, or OR.sup.7 wherein R.sup.7 is hydrogen, alkyl, aryl, acyl, or aralkyl, or taken together with the adjacent nitrogen atom may form heterocyclic group which may contain N, O, and/or S, and X and Y each is independently O, S, substituted or unsubstituted imino, or substituted or unsubstituted methylene, give advantageous anti-inflammatory activities applicable to an agent for treating chronic inflammation, and that side effects thereof, e.g., stomach disease, are extremely weaker than prior anti-inflammatory agents, whereby they have completed the present invention. The present invention is characterized by its potent inhibitory activities against the production of IL-1.
In the present specification, "alkyl" means straight or branched C.sub.1 -C.sub.10 alkyl, and preferred is straight or branched C.sub.1 -C.sub.6 alkyl, including, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, i-pentyl, neopentyl, s-pentyl, t-pentyl, n-hexyl, neohexyl, i-hexyl, s-hexyl, t-hexyl, and the like.
As alkyl meant in the definition for R.sup.1 and R.sup.2, most preferred is branched C.sub.3 or C.sub.4 alkyl, i.e., i-propyl or t-butyl. As alkyl meant in the definition for R.sup.4, especially preferred is C.sub.1 or C
REFERENCES:
patent: 3485632 (1969-12-01), Ohlschlager et al.
patent: 3624081 (1971-11-01), Dickinson et al.
patent: 3686204 (1972-08-01), Munz et al.
patent: 4153713 (1979-05-01), Huth et al.
patent: 4861794 (1989-08-01), Otterness
patent: 5191084 (1993-03-01), Bagli et al.
Haga Nobuhiro
Jyoyama Hirokuni
Kamata Susumu
Matsumoto Saichi
Okada Toshihiko
Higel Floyd D.
Shionogi Seiyaku Kabushiki Kaisha
LandOfFree
3-benzylidene-1-carbamoyl-2-pyrrolidone compounds useful as anti does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 3-benzylidene-1-carbamoyl-2-pyrrolidone compounds useful as anti, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 3-benzylidene-1-carbamoyl-2-pyrrolidone compounds useful as anti will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-793826