Patent EA-004291-B1 (EA)
Title: Novel derivatives of 3-imino-1,2-dithioles, method for producing them and pharmaceutical compositions containing the same
Inventor: DUFLOS MURIEL
IPC: C07D213/74
Filed: 2000-12-21
Abstract: 1. Compound of formula (I): wherein: Het1 and Het2, which may be identical or different, each represents a heteroaryl group, A represents a bond or a linear or branched (C1-C6)alkylene group, its optical isomers, where they exist, and addition salts thereof with a pharmaceutically acceptable acid, wherein a heteroaryl group is to be understood as meaning an aromatic mono- or bi-cyclic group having from 5 to 12 ring members containing one, two or three hetero atoms selected from oxygen, nitrogen and sulphur, wherein the heteroaryl group may optionally be substituted by one or more identical or different atoms or groups selected from the halogen atoms and the groups linear or branched (C1-C6)alkyl, hydroxy, linear or branched (C1-C6)alkoxy, linear or branched (C1-C6)polyhaloalkyl, nitro and amino (optionally substituted by one or more linear or branched (C1-C6)alkyl groups). 2. Compound of formula (I) according to claim 1, wherein Het1 represents an optionally substituted pyridyl group, its optical isomers, where they exist, and its addition salts with a pharmaceutically acceptable acid. 3. Compound of formula (I) according to claim 1, wherein Het2 represents an optionally substituted pyridyl group, its optical isomers, where they exist, and its addition salts with a pharmaceutically acceptable acid. 4. Compound of formula (I) according to claim 1, which is 3-(3-pyridyl)-5-[N-(4,6-dimethyl-2-pyridyl)-imino]-1,2-dithiol, and addition salts thereof with a pharmaceutically acceptable acid. 5. Process for the preparation of compounds of formula (I) according to claim 1, characterised in that a compound of formula (II): wherein Het1 has the same meaning as in formula (I) and R1 represents a linear or branched (C1-C6)alkyl group, is reacted with a compound of formula (III): H2N-A-Het2 (III) wherein Het2 and A have the same meanings as in formula (I), to yield a compound of formula (IV): wherein Het1, Het2 and A have the same meanings as in formula (I), which is reacted with a thionation agent to yield a compound of formula (I), which is purified, if necessary, according to a conventional purification technique, and which is converted, if desired, into addition salts with a pharmaceutically acceptable acid. 6. Process according to claim 5 for the preparation of 3-(3-pyridyl)-5-[N-(4,6-dimethyl-2-pyridyl)-imino]-1,2-dithiol, characterised in that a compound of formula (IIa), a particular case of the compounds of formula (II): wherein R1 has the same meaning as hereinbefore, is reacted with the compound of formula (IIIa), a particular case of the compounds of formula (III): to yield the compound of formula (IVa), a particular case of the compounds of formula (IV): which is reacted with a thionation agent, such as, for example, Lawesson's reagent, to yield 3-(3-pyridyl)-5-[N-(4,6-dimethyl-2-pyridyl)-imino]-1,2-dithiol, which is purified according to a conventional purification technique, and which is converted, if desired, into addition salts with a pharmaceutically acceptable acid. 7. Synthesis intermediate of 3-(3-pyridyl)-5-[N-(4,6-dimethyl-2-pyridyl)-imino]-1,2-dithiol, which is N-(4,6-dimethyl-2-pyridyl)-3-oxo-3-(3-pyridyl)-propionamide. 8. Pharmaceutical compositions comprising as active ingredient a compound according to any one of claims 1 to 4, alone or in combination with one or more pharmaceutically acceptable, inert, non-toxic carriers. 9. Pharmaceutical compositions according to claim 8, for use in the manufacture of anti-inflammatory medicaments. 10. Pharmaceutical compositions according to claim 9, for use in the manufacture of medicaments useful in the treatment of psoriasis.