Patent EA-003023-B1 (EA)
Title: New aminotriazole compounds, a process for their preparation and pharmaceutical compositions containing them
Inventor: FAUCHERE JEAN-LUC
IPC: A61P3/00
Filed: 2000-04-14
Abstract: 1. The compounds formula (I):   wherein n is 0 or 1, W represents group -CO- or group S(O)q wherein q is 0, 1 or 2, fragment of the formula   the group, selected from   Z represents alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted arylalkenyl, optionally substituted arylalkynyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl or optionally substituted heteroarylalkyl group, A represents fragment of formula selected from -A2-, -A1-A2-, -A2-A1- and -A1-A2-A1-, wherein A1 represents alkylen group and A2 represents optionally substituted phenylene, optionally substituted naphtylene, cycloalkylene, or optionally substituted heteroarylene group, R represents hydrogen atom or alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted arylalkenyl , optionally substituted arylalkynyl, optionally substituted heteroarylalkenyl , or optionally substituted heteroarylalkynyl, or optionally substituted heteroarylalkyl group, R1 represents alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted arylalkenyl, optionally substituted arylalkynyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, or optionally substituted heteroarylalkyl group, enantiomers, diastereoisomers or addition salts of pharmaceutically acceptable acids or bases thereof, wherein: - "alkyl" represents the group with straight or branched chain comprising from 1 to 6 carbon atoms, - "alkylene" represents bivalent radical with straight or branched chain, comprising from 1 to 6 carbon atoms, - "alkenyl" represents the group with straight or branched chain comprising from 2 to 6 carbon atoms and from 1 to 3 double bonds, - "alkynyl" represents the group with straight or branched chain comprising from 2 to 6 carbon atoms and from 1 to 3 triple bonds, - "aryl" represents phenyl, napthyl, biphenyl, dihydronapthyl, or tetrahydronapthyl, - "heteroaryl" represents unsaturated or partly unsaturated mono- or bicyclic group having 5 to 11 members in the ring, comprising from 1 to 4 heteroatomes selected from nitrogen, oxygen or sulfur such as pyridyl, pyridazinyl, furyl, thienyl, pyrrolyl, - terms "phenylene" or "naphtylene" represent bivalent phenyl or naphtyl radicals correspondingly, - "cycloalkylene" represents bivalent saturated cyclic radical comprising 3 to 8 carbon atoms, - "heteroarylene" represents bivalent heteroaryl radical, as it is determined above, - expression "optionally substituted" in respect of "aryl", "arylalkyl", "heteroaryl", or "heteroarylalkyl" means that these groups are substituted on their cyclic fragment with 1 to 3 similar of different substituents, selected from (C1-C6) alkyl with linear or branched chain; (C1-C6)alkoxy with linear or branched chain; halogen; hydroxy; perhalogen(C1-C6)alkyl with linear or branched chain; nitro; amino (optionally substituted with one or two groups (C1-C6)alkyl with linear or branched chain); (C1-C6) acyl with linear or branched chain; aminocarbonyl (optionally substituted on nitrogen atom with one or two groups (C1-C6) alkyl with linear or branched chain); (C1-C6)acylamino with linear or branched chain; (C1-C6)alkoxycarbonyl with linear or branched chain; formyl; carboxy; sulfo; nitril; (C1-C6)aminoalkyl with linear or branched chain (optionally substituted on nitrogen atom with one or two groups (C1-C6) alkyl with linear or branched chain); (C1-C6)thioalkyl with linear or branched chain (optionally substituted on sulfur atom with (C1-C6)alkyl group with linear or branched chain); or (C1-C6)hydroxyalkyl with linear or branched chain (optionally substituted on oxygen atom with (C1-C6) alkyl group with linear or branched chain); - expression "optionally substituted" in respect of "phenylene", "naphtylene" or "heteroarylene" means that these groups are substituted with one-three similar or different groups, selected from (C1-C6)alkyl with linear or branched chain; (C1-C6)alkoxy with linear or branched chain; halogen; hydroxy; perhalogen(C1-C6)alkyl with linear or branched chain; nitro; amino (optionally substituted with one or two groups (C1-C6)alkyl with linear or branched chain); (C1-C6)acyl with linear or branched chain; formyl; carboxy; (C1-C6)alkoxycarbonyl with linear or branched chain; aminocarbonyl (optionally substituted on nitrogen atom with one or two groups (C1-C6) alkyl with linear or branched chain); (C1-C6)acylamino with linear or branched chain; or nitrile. 2. The compounds of formula (I) according to Claim 1, wherein n is 1, enantiomers, diastereoisomers or addition salts of pharmaceutically acceptable acid or base thereof. 3. The compounds of formula (I) according to Claim 1, wherein n is 0, enantiomers, diastereoisomers or addition salts of pharmaceutically acceptable acid or base thereof. 4. The compounds of formula (I) according to Claim 1, wherein W is group SO2 enantiomers, diastereoisomers or addition salts of pharmaceutically acceptable acid or base thereof. 5. The compounds of formula (I) according to Claim 1, wherein fragment of formula  , represents the group selected from   enantiomers, diastereoisomers or addition salts of pharmaceutically acceptable acid or base thereof. 6. The compounds of formula (I) according to Claim 1, wherein fragment of formula  , represents the group selected from    enantiomers, diastereoisomers or addition salts of pharmaceutically acceptable acid or base thereof. 7. The compounds of formula (I) according to Claim 1, wherein A is a fragment of formula A2, enantiomers, diastereoisomers or addition salts of pharmaceutically acceptable acid or base thereof. 8. The compounds of formula (I) according to Claim 1, wherein A is a fragment of formula -A1-A2-, or -A2-A1-, enantiomers, diastereoisomers or addition salts of pharmaceutically acceptable acid or base thereof. 9. The compounds of formula (I) according to Claim 1, wherein R1 represents optionally substituted aryl group, enantiomers, diastereoisomers or addition salts of pharmaceutically acceptable acid or base thereof. 10. The compounds of formula (I) according to Claim 1, wherein R is selected from hydrogen atom or optionally substituted aryl group, or optionally substituted heteroaryl group, enantiomers, diastereoisomers or addition salts of pharmaceutically acceptable acid or base thereof. 11. The compounds of formula (I) according to Claim 1, wherein Z represents a group selected from alkyl, optionally substituted aryl, or optionally substituted heteroaryl group, enantiomers, diastereoisomers or addition salts of pharmaceutically acceptable acid or base thereof. 12. The compounds of formula (I) according to Claim 1, wherein n is 1, W represents a group SO2, A represents a group selected from phenylene, pyridinylene or pyrazinylene, R1 represents optionally substituted aryl group, R is selected from hydrogen atom or optionally substituted aryl group, or optionally substituted heteroaryl group, or Z represents alkyl, optionally substituted aryl group, or optionally substituted heteroaryl group, enantiomers, diastereoisomers or addition salts of pharmaceutically acceptable acid or base thereof. 13. The compound of formula (I) according to Claim 1, which is N'-[4-({5-phenyl-1-[3-(trifluoromethyl)phenyl]-1H-1,2,4-triazol-3-yl}amino)benzoyl]benzenesulfonohydrazide. 14. The compound of formula (I) according to Claim 1, which is N'-{4-[(5-phenyl-1H-1,2,4-triazol-3-yl)amino]benzoyl}benzenesulfonohydrazide. 15. The compound of formula (I) according to Claim 1, which is N'-(4-{[5-phenyl-1-(2-pyridyl)-1H-1,2,4-triazol-3-yl)amino}benzoyl)-benzenesulfonohydrazide. 16. The compound of formula (I) according to Claim 1, which is N'-[4-({5-oxo-1-[3-(trifluoromehyl)phenyl]-4,5-dihydro-1H-1,2,4-triazol-3-yl}amino)benzoyl}benzenesulfonohydrazide. 17. The compound of formula (I) according to Claim 1, which is N'-(4-{[5-oxo-1-(2-pyridyl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]amino}benzoyl)benzenesulfonohydrazide. 18. The compound of formula (I) according to Claim 1, which is N'-[(6-{[5-oxo-1-(2-pyridinyl)-4,5-dihydro-1H-1,2,4-triazol-3-yl]amino}-3-pyridinyl)carbonyl]benzenesulfonohydrazide. 19. The process for preparation of compounds of formula (I) according to Claim 1, characterized in that as starting material the compound of formula (II) is used:   wherein A is determined for formula (I), and P represents protecting group for aminofunction, which reacts in presence of linking agent with the compound of formula (III):   wherein n, W or Z are as determined for formula (I), with obtaining after aminofunction deprotection by removing P group, the compound of formula (IV)   wherein n, A, W and Z are such as determined above, and the compound (IV) is further condensed in alkaline medium with isothiocyanate of formula (V):   wherein R'1 is as determined above for R1 in formula (I), or is (C1-C6) alkoxy group with linear or branched chain, obtaining the compound of (VI):   wherein n, R'1, A, W and Z are such as determined above, and the compound of formula (VI): either when R'1 represents (C1-C6) alkoxy group is condensed in presence of condensing agent with hydrazine of formula R-NH-NH2, wherein R is determined for formula (I) with obtaining the compound of formula (VII/a):     wherein R, A, n, W or Z are such as determined above, and R'1 represents (C1-C6)alkoxy group with linear or branched chain, at that the composition (VII/a) is cyclizated spontaneously or after treatment in acid medium depending on nature of R group, giving the mixture of two compounds of formula (I/a) and (I/b):     particular cases of compounds of formula (I) wherein R, A, n, W and Z are such as determined above, at that compounds (I/a) and (I/b) can be separated in accordance with standard methods of separation, - or when R'1 represents R1, as it is determined for formu