Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1990-07-10
1992-04-21
Morris, Patricia L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
544 582, A61K 3154, C07D27912
Patent
active
051068460
DESCRIPTION:
BRIEF SUMMARY
This invention relates to novel 2,3-thiomorpolinedione-2-oxime-derivatives of the general formula (I), ##STR2## wherein R.sub.1 stands for hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy or nitro group; or oxo group; or an ester group containing 1 to 4 carbon atoms in the alkoxy moiety; or a C.sub.1-4 alkoxy, cyano, amino, C.sub.1-4 alkylamino, or dialkylamino group; or an acyl group containing 1 to 7 carbon atoms in the alkyl moiety; or substituents defined above for R.sub.2 in the alkyl chain and optionally substituted by halogen, nitro, C.sub.1-4 alkyl or alkoxy group in the benzene ring; or latter groups optionally being substituted by halogen or a C.sub.1-4 alkyl group in the benzene ring; or alkyl group(s) or phenyl group on the nitrogen atom
The compounds of the general formula (I) have interesting cytoprotective and gastric acid secretion-inhibiting properties and are effective against gastric and duodenal ulcers.
The therapeutic importance of the above new compounds is very high since the number of patients suffering from gastric and duodenal ulcer is continuously increasing both in the absolute and relative sense as well. Although a number of drugs are known which are useful for the ulcer therapy, no similar effect has up to the present been described for 2,3-thiomorpholinedione-2-oximes.
According to the literature, several patents (U.S. Pat. Nos. 3,790,566, 3,883,510, 3,894,150, 3,930,002, 4,003,895 and 4,003,897) describing 2,3-thiomorpholinedione-2-oxime derivatives as pesticides were granted for the Union Carbide and the du Pont companies; however, no benzyl group substituted by R.sub.1 was bound to the ring nitrogen in the compounds of these patents.
Thus, the aim of the present invention was to find novel, therapeutically useful compounds which can be prepared economically on an industrial scale, too.
Accordingly the invention relates also to a process for the preparation of the new compounds of general formula (I), ##STR3## wherein R.sub.1 stands for hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy or nitro group; or oxo group; or an ester group containing 1 to 4 carbon atoms in the alkoxy moiety; or a C.sub.1-4 alkoxy, cyano, amino, C.sub.1-4 alkylamino, or dialkylamino group; or an acyl group containing 1 to 7 carbon atoms in the alkyl moiety; or substituents defined above for R.sub.2 in the alkyl chain and optionally substituted by halogen, nitro, C.sub.1-4 alkyl or alkoxy group in the benzene ring; or latter groups optionally being substituted by halogen or a C.sub.1-4 alkyl group in the benzene ring; or alkyl group(s) or phenyl group on the nitrogen atom
a) to obtain compounds of the general formula (I) containing as R.sub.2 a substituent different from an N-substituted carbamoyl group reacting a compound of the general formula (II), ##STR4## wherein R.sub.1 is as defined above, in an inert organic solvent in the presence of an inorganic or organic base with a compound of the general formula (III), carbamoyl group and X is halogen or, when the meaning of R.sub.3 is different from an acylatable group, X may be also a mesyloxy or tosyloxy group; or
b) to obtain compounds of the general formula (I) containing an N-substituted cabamoyl group as R.sub.2, reacting a compound of the general formula (II), wherein R.sub.1 is as defined above, in an inert organic solvent in the presence of an organic tertiary amine, preferably triethylamine with a compound of the general formula (IV),
The preparation of the 2,3-thiomorpholinedione-2-oxime derivatives of general formula (II) used as starting substances has been described in our patent application simultaneously filed. According to those reported in that patent application, the compounds of the general formula (II) can be prepared e.g. by reacting an appropriately substituted 2-nitromethylene-3-(phenylmethyl)thiazolidine with a basic reagent in an aqueous and/or alcoholic medium.
From the 2,3-thiomorpholinedione-2-oxime derivatives of the general formula (II), the compounds according to the present invention can be prepared by the metho
REFERENCES:
patent: 3790566 (1974-02-01), Bellina
patent: 3883510 (1975-05-01), Bellina
patent: 3894150 (1975-07-01), Durden, Jr.
patent: 3930002 (1975-12-01), Durden, Jr.
patent: 4003895 (1977-01-01), Durden, Jr.
patent: 4003897 (1977-01-01), Durden
Chemical Abstracts, vol. 90, No. 11, issued Mar. 12, 1979, abstract No. 90:821-62Z, p. 172, column 1, CA 90:82162Z.
Domany Gyorgy
Ezer Elemer
Hajos Gyorgy
Harsanyi Kalman
Hegedus Bela
Morris Patricia L.
Richter Gedeon Vegyeszeti Gyar Rt
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