Patent EA-003424-B1 (EA)
Title: Novel derivatives of 1,2-dithiolane, process for preparing them and pharmaceutical compositions containing them
Inventor: GOLDSTEIN SOLO
IPC: C07D339/04
Filed: 1999-12-14
Abstract: 1. A compound selected from those of the formula (I): wherein: Ra represents linear or branched (C1 -C8)alkylene, Rb represents a single bond, or linear or branched (C1 -C6)alkylene, Z represents: - thiocarbamate wherein the oxygen is bonded to Ra, and R1 represents a group selected from hydrogen, or thioamide wherein thiocarbonyl is bonded to Ra, and R1 is as defined hereinbefore, T represents a group wherein R2 and R3, which may be identical or different, each independently of the other represents a group selected from hydrogen, linear or branched (C1 -C6)alkyl, aryl, aryl(C1-C6)alkyl in which alkyl is linear or branched, its isomers, and pharmaceutically-acceptable acid or base addition salts thereof. 2. Compounds of formula (I) by claim 1, characterized in that they represent compounds of formula (IA): wherein all substitutes have the values, defined in claim 1, its isomers, and pharmaceutically-acceptable acid or base addition salts thereof. 3. Compounds of formula (I) by claim 1, characterized in that they represent compounds of formula (IB): wherein all substitutes have the values, defined in claim 1, its isomers, and pharmaceutically-acceptable acid or base addition salts thereof. 4. Compounds of formula (I) by any of claims 1-3, characterized in that Z represents thiocarbamate: wherein R1 has the value, defined in claim 1, its isomers, and pharmaceutically-acceptable acid or base addition salts thereof. 5. Compounds of formula (I) by any of claims 1-4, characterized in that Z represents thiocarbamate: its isomers, and pharmaceutically-acceptable acid or base addition salts thereof. 6. Compounds of formula (I) by any of claims 1-3, characterized in that T represents a group wherein R2 and R3 have the values, defined in claim 1, its isomers, and pharmaceutically-acceptable acid or base addition salts thereof. 7. A compound of formula (I) by claim 6, wherein R2 and R3, which are identical, represent hydrogen, its isomers, and pharmaceutically-acceptable acid or base addition salts thereof. 8. A compound of formula (I) by claim 1 or 2, which is 5-(1,2-dithiolan-3-yl)pentyl N-(2-morpholinoethyl) thiocarbamate hydrochloride. 9. A compound of formula (I) by claim 1 or 2, which is 5-[(3S)-1,2-dithiolan-3-yl]pentyl N-(2-morpholinoethyl) thiocarbamate hydrochloride. 10. A compound of formula (I) by claim 1 or 2, which is 5-[(3R)-1,2-dithiolan-3-yl]pentyl N-(2-morpholinoethyl) thiocarbamate hydrochloride. 11. A compound of formula (I) by claim 1 or 2, which is 5-(1,2-dithiolan-3-yl)pentyl N-(3-morpholinopropyl) thiocarbamate hydrochloride. 12. A compound of formula (I) by claim 1 or 2, which is 5-(1,2-dithiolan-4-yl)pentyl N-(2-morpholinoethyl) thiocarbamate hydrochloride. 13. A method of preparation of compounds of formula (I), characterized in that as a starting material is used a compound of formula (II): wherein Ra is as defined for formula (I), which is treated in alkaline medium with compound of formula (III): wherein R1, Rb, and T are as defined for formula (I), bringing to obtaining of compounds of formula (IV): wherein Ra, R1, Rb, and T are as defined earlier, which is subjected to effect of Lowersson's reagent, in order to obtain compounds of formula (I/a), particular case of compounds of formula (I): wherein Ra, R1, Rb, and T are as defined earlier, received compounds of formula (I/a) are cleaned, if necessary, using common refinement procedures, are divided if necessary on its different isomers, using common division procedures, and are converted, where it's appropriate, its isomers, and pharmaceutically-acceptable acid or base addition salts thereof. 14. A method of preparation of compounds of formula (I), characterized in that as a starting material is used a compound of formula (V): wherein Ra is as defined for formula (I), which is reacting in presence of bis(tributyl)oxide, with thioisocyanat of formula (IV): S = C = N - Rb - T (IV) Wherein Rb, and T are as defined for formula (I), bringing to obtain compounds of formula (I/b), particular case of formula (I): wherein Ra, Rb, and T are as defined earlier, which is treated, if desired, with compound of formula (VII): R1 - X (VII) wherein R1 is as defined for formula (1), and X represents halogen, bringing to obtain compounds of formula (I/c), particular case of compounds of formula (I): wherein Ra, R1, Rb, and T are as defined earlier, received compounds(I/b and I/c) of formula (I/a) are cleaned, if necessary, using common refinement procedures, are divided if necessary on its different isomers, using common division procedures, and are converted, where it's appropriate, its isomers, and pharmaceutically-acceptable acid or base addition salts thereof. 15. A pharmaceutical composition comprising as active ingredient at least one compound of formula (I) by any of claims 1-12 independently, or in combination with one or more inert, non-toxic pharmaceutically-acceptable excipients or carriers. 16. A pharmaceutical composition by claim 15, comprising at least one active ingredient by any of claims 1-12, used as an anti-oxidation agent.