Organic compounds -- part of the class 532-570 series – Organic compounds – Azo
Patent
1986-07-03
1988-02-16
Higel, Floyd D.
Organic compounds -- part of the class 532-570 series
Organic compounds
Azo
534728, 534787, A61K 31655, C07C10706, C07D30783
Patent
active
047256761
DESCRIPTION:
BRIEF SUMMARY
The present invention is concerned with novel compounds having a potentially inhibitory effect on 15-hydroxyprostaglandin dehydrogenase (PGDH). The invention is also concerned with the production of these novel compounds and with pharmaceutical compositions containing them.
The future potentialities of PGDH inhibitors, in respect of their usefulness in medicine, have not yet been fully explored. But it is a known fact that prostaglandins play a very important role in the body's regulating system, and for this reason any drugs interfering with either the synthesis or the degradation of prostaglandins may be potentially valuable medical tools. The so-called cytoprotective effect of prostaglandins is relatively well known in the context of ulcer therapies; but neverthless prostaglandin administration has not been utilized to any major extent for therapeutic purposes because the prostaglandins administered with survive in vivo for only a very short time. A drug inhibiting the degradation of endogenous prostaglandins might conceivably be much more successful than prostaglandin administration.
Endogenous prostaglandins have a major role also in inflammatory processes. In the treatment of rheumatoid arthritis it is therefore at present quite a common practice to employ inhibitors of prostaglandin synthesis; but nowadays this is regarded as merely being a symptomatic treatment, and as a matter of fact some of the prostaglandins are now believed to possibly have a very favorble effect. Thus in this context, too, the inhibition of PGDH dependent degradation may be potentially very valuable. Further potentially valuable medical fields of application for the present novel compounds are all those where prostaglandins may function as desirable controlling factors as e.g. in the case of circulatory disorders, cancer, fertility, cell regulation etc.
Examples of previously known compounds having an inhibitory effect on PGDH are such azo compounds as are set forth in No. EP-A-21229 and novel arylacetic acid derivatives set forth in Swedish patent application No. 8400239-3.
It is an object of the present invention to provide improved PGDH inhibitors and methods for their production. Further objects are to provide improved pharmaceutical compositions and treating methods involving such inhibitors.
The novel compounds of the present invention have the following structure: ##STR2## in which X, Y and Z are hydrogen, carboxy or lower alkoxycarbonyl, one of X, Y and Z always being hydrogen and the others being identical or different groups.
The invention comprises also lactones of compounds (I) and salts thereof. The preferred salts are pharmaceutically acceptable and therapeutically active.
By lower alkoxy groups are meant those having less than seven carbon atoms.
Suitable salts are metal salts such as the sodium, potassium and calcium salts, or salts with organic amines such as e.g. diethanolamine, triethanolamine, N-methyl-glucamine, trishydroxymethyl-methylamine etc.
A major advantage of the compounds according to the present invention resides in that they comprise groups greatly varying inter se in respect to their capacity of being absorbed from the gastrointestinal tract. This means that the invention comprises i.a. compounds which are rapidly and completely absorbed into the bloodstream--which is a valuable feature for obtaining a systemic effect. Other compound, on the other hand, have a very low capacity for being absorbed and consequently will concentrate to the gastrointestinal tract; so this in turn means that some compunds of formula (I) may have a potential local activity against gastrointestinal disorders such as for instance gastric ulcer, Crohn's disease and ulcerous colitis.
It has been found, surprisingly, that the novel compounds are extremely potent inhibitors of the enzyme PGDH. Moreover an important feature of these compounds is that they are highly selective in their effect: Their inhibition of cyclooxygenase is practically zero. The invention permits treatments with very low doses of the active substance
REFERENCES:
patent: 3236829 (1966-02-01), May et al.
patent: 3244694 (1966-04-01), May et al.
patent: 3251822 (1966-05-01), May et al.
patent: 4412992 (1983-11-01), Chan
Berry et al, Biochemical Pharmacol., vol. 32, pp. 2863 to 2871 (1983).
Moore et al, Biochemical Pharmacol., vol. 31, pp. 969 to 971 (1982).
Agback Karl H.
Nygren Alf S.
Higel Floyd D.
Pharmacia AB
Philpitt Fred
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