1. A compound of the formula (I):
in which:
X represents a group
R1 represents:
a (C6-C12)alkyl;
a nonaromatic (C3-C12) carbocyclic radical which is unsubstituted or substituted once or several times with a (C1-C4)alkyl;
a methyl which is substituted with a nonaromatic C3-C12 carbocyclic radical and which is unsubstituted or substituted once or several times on the carbocycle with a (C1-C4)alkyl;
a phenyl which is mono-, di- or -trisubstituted with substituents independently chosen from a halogen atom, a (C1-C4)alkoxy, a (C1-C4)alkylamino, a di-(C1-C4)alkylamino, a cyano, a trifluoromethyl radical, a trifluoromethoxy radical, an S(O)nAlk group, a (C1-C4)alkylcarbonyl group, and methylenedioxy;
or substituents chosen from phenyl, phenoxy, pyrrolyl, imidazolyl, pyridyl and pyrazolyl radical, said radicals being unsubstituted or substituted once or several times with a (C1-C4)alkyl;
a benzyl which is mono- or disubstituted on the phenyl with substituents independently chosen from a halogen atom, a (C1-C4)alkyl, a (C1-C4)alkoxy, a trifluoromethyl radical, and (trifluoromethyl)thio radical;
or the phenyl substituted at the alpha-position with one or two similar or different groups chosen from a (C1-C4)alkyl, a (C3-C7)cycloalkyl, or a pyrrolyl radical;
a phenethyl which is unsubstituted or mono- or disubstituted on the phenyl with substituents independently chosen from the halogen atom, a (C1-C4)alkyl, a (C1-C4)alkoxy, and a trifluoromethyl radical;
a 1,2,3,4-tetrahydronaphthyl or a 5,6,7,8-tetrahydronaphthyl which is unsubstituted or mono- or disubstituted with substituents independently chosen from a (C1-C4)alkyl, a (C1-C4)alkoxy and a trifluoromethyl radical;
a benzhydryl; or a benzhydrylmethyl;
R2 represents a hydrogen atom or a (C1-C3)alkyl;
R3 represents a phenyl which is unsubstituted or mono-, di- or trisubstituted with substituents independently chosen from a halogen atom, a (C1-C4)alkyl, a (C1-C4)alkoxy, a trifluoromethyl radical or an S(O)nAlk group;
R4 represents a phenyl which is unsubstituted or mono-, di- or trisubstituted with substituents independently chosen from a halogen atom, a (C1-C4)alkyl, a (C1-C4)alkoxy, a trifluoromethyl radical or an S(O)nAlk group;
R5 represents a hydrogen atom or a (C1-C3)alkyl;
n represents 0, 1 or 2; and
Alk represents a (C1-C4)alkyl;
or a hydrate or a solvate thereof.
2. The compound of formula (I) according to claim 1, in which \u2014X\u2014 represents a \u2014CO\u2014 radical and the substituents R1 to R4 are as defined for the compounds of formula (I) in claim 1;
or a hydrate or a solvate thereof.
3. The compound of formula (I) according to claim 1, in which \u2014X\u2014 represents a \u2014CON(R5)\u2014 radical and the substituents R1 to R5 are as defined for the compounds of formula (I) in claim 1;
or a hydrate or a solvate thereof.
4. The compound of formula (I) according to claim 1, in which \u2014X\u2014 represents a \u2014CSN(R5)\u2014 radical and the substituents R1 to R5 are as defined for the compounds of formula (I) in claim 1;
or a hydrate or a solvate thereof.
5. The compound of formula (I) according to claim 1, in which:
X represents a \u2014CO\u2014 group, a \u2014CONH\u2014 group or a \u2014CSNH\u2014 group;
R1 represents:
a 1-propylbutyl; a 1-ethylpentyl; a 1-methylpentyl;
a cycloheptyl; a 1-methylcyclopropyl; a cyclobutyl; a cyclopentyl; a cyclohexyl; a 1-methylcyclohexyl; a bicyclo2.2.1hept-2-yl; a bicyclo2.2.1hept-5-en-2-yl;
a cyclohexylmethyl; a cycloheptylmethyl; a bicyclo2.2.1hept-2-ylmethyl;
a 4-bromophenyl; a 4-chlorophenyl; a 2-fluorophenyl; a 3-fluorophenyl; a 4-fluorophenyl; a 3,5-difluorophenyl; a 2,5-difluorophenyl; a 2-methoxyphenyl; a 3-methoxyphenyl; a 3-cyanophenyl; a 4-cyanophenyl; a 3-(trifluoromethyl)-phenyl; a 4-(trifluoromethyl)phenyl: a 4-(trifluoromethoxy)phenyl; a 3-acetylphenyl; a biphenyl-2-yl; a biphenyl-4-yl; a 1,3-benzodioxol-5-yl; a 4-phenoxyphenyl; a 4-(1H-pyrrol-1-yl)phenyl;
a 2-fluorobenzyl; a 3-fluorobenzyl; a 4-fluorobenzyl; a 4-(trifluoromethyl)benzyl; a 4-(trifluoromethyl)thiobenzyl; an \u03b1-cyclohexylbenzyl; an \u03b1-(1H-pyrrol-1-yl)benzyl;
a 4-(trifluoromethyl)phenethyl;
a benzhydryl; a benzhydrylmethyl;
a 1,2,3,4tetrahydronaphth-2-yl; a 1,2,3,4-tetrahydronaphth-1-yl; or a 5,6,7,8-tetrahydronaphth-1-yl;
R2 represents a hydrogen atom or a methyl;
R3 represents a 4-bromophenyl; a 4-chlorophenyl; a 2,4-dichlorophenyl; or a 4-methoxyphenyl; and
R4 represents a 4-chlorophenyl; a 2,4 dichlorophenyl; a 4-methoxyphenyl;
or a hydrate or a solvate thereof.
6. The compound of formula (I) according to claim 1, in which:
X represents a \u2014CO\u2014 group or a \u2014CONH\u2014 group;
R1 represents:
a 1-propylbutyl; a 1-ethylpentyl; a 1-methylpentyl;
a cycloheptyl;
a cycloheptylmethyl; or
a biphenyl-2-yl;
R2 represents a hydrogen atom or a methyl;
R3 represents a 4-bromophenyl; a 4-chlorophenyl; or a 2,4-dichlorophenyl;
R4 represents a 4-chlorophenyl; or a 2,4-dichlorophenyl;
or a hydrate or a solvate thereof.
7. The compound of formula (I) according to claim 1, chosen from:
N-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-2-propylpentanamide;
N-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-2-ethylhexanamide;
N-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-2-methylhexanamide;
N-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-cycloheptanecarboxamide;
N-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-2-cycloheptylacetamide;
N-biphenyl-2-yl-N\u2032-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethylurea;
N-4-(4-bromophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-2-propylpentanamide;
N-4-(4-bromophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-2-methylhexanamide;
N-4-(4-bromophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-2-ethylhexanamide;
N-4-(4-bromophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-cycloheptanecarboxamide;
N-4-(4-bromophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-N-methylcycloheptanecarboxamide;
N-4-(4-bromophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-2-cycloheptylacetamide;
N-4-(4-bromophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-2-cycloheptyl-N-methylacetamide;
N-5-(4-chlorophenyl)-4-(2,4-dichlorophenyl)-2-thienylmethyl-cycloheptanecarboxamide;
N-5-(4-chlorophenyl)-4-(2,4-dichlorophenyl)-2-thienylmethyl-N-methylcycloheptanecarboxamide;
N-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-1-methylcyclohexanecarboxamide;
4-chloro-N-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethylbenzamide;
N-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-4-(trifluoromethyl)benzamide;
1-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethyl-3-(4-fluorophenyl)urea;
1-(4-bromophenyl)-3-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-thienylmethylurea;
N-5-(2,4-dichlorophenyl)-4-(4-methoxyphenyl)-2-thienylmethylbicyclo2.2.1heptane-2-carboxamide;
N-5-(2,4-dichlorophenyl)-4-(4-methoxyphenyl)-2-thienylmethyl-2-propylpentanamide; and
N-4-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-2-thienylmethyl-2-propylpentanamide;
or a hydrate or a solvate thereof.
8. A method for preparing the compounds of formula (I) according to claim 1, comprising:
treating a compound of formula (II):
in which R2, R3 and R4 are as defined for a compound of formula (I) in claim 1,
either with an acid of formula (III) or a functional derivative of this acid:
HOOC\u2014R1 \u2003\u2003(III)
in which R1is as defined for a compound of formula (I) in claim 1, when a compound of formula (I) has to be prepared in which \u2014X\u2014 represents an \u2014CO\u2014 group;
or with a haloformate of formula (IV):
HalCOOAr \u2003\u2003(IV)
in which Hal represents a halogen atom and Ar represents a phenyl or a 4-nitrophenyl, to give an intermediate compound of formula (V):
in which R2, R3 and R4 are as defined for a compound of formula (I) in claim 1; reacting a compound of formula (V) thus formed with an amine of formula (VI):
HN(R5)R1 \u2003\u2003(VI)
in which R1 and R5 are as defined for a compound of formula (I), when a compound of formula (I) has to be prepared in which \u2014X\u2014 represents a \u2014CON(R5)\u2014 group;
or with an isothiocyanate of formula (XX):
S\u2550C\u2550N\u2014R1 \u2003\u2003(XX)
in which R1 is as defined for a compound of formula (I) in claim 1, when a compound of formula (I) has to be prepared in which \u2014X\u2014 represents a \u2014CSNH\u2014 group.
9. A pharmaceutical composition comprising a compound of formula (I) according to claim 1 or a hydrate or a solvate of this compound and at least one pharmaceutically acceptable excipient.
10. A pharmaceutical composition comprising a compound of formula (I) according to claim 2 or a hydrate or a solvate of this compound and at least one pharmaceutically acceptable excipient.
11. A pharmaceutical composition comprising a compound of formula (I) according to claim 3 or a hydrate or a solvate of this compound and at least one pharmaceutically acceptable excipient.
12. A pharmaceutical composition comprising a compound of formula (I) according to claim 4 or a hydrate or a solvate of this compound and at least one pharmaceutically acceptable excipient.
13. A pharmaceutical composition comprising a compound of formula (I) according to claim 5 or a hydrate or a solvate of this compound and at least one pharmaceutically acceptable excipient.
14. A pharmaceutical composition comprising a compound of formula (I) according to claim 6 or a hydrate or a solvate of this compound and at least one pharmaceutically acceptable excipient.
15. A pharmaceutical composition comprising a compound of formula (I) according to claim 7 or a hydrate or a solvate of this compound and at least one pharmaceutically acceptable excipient.
16. A method of treatment of appetite disorder, gastrointestinal disorder, inflammatory phenomena, immune system disease, psychotic disorder, alcohol dependence and nicotine dependence comprising administering to a patient in need of said treatment a therapeutically effective amount of a compound of formula (I) according to claim 1.
17. A method of treatment of appetite disorder, gastrointestinal disorder, inflammatory phenomena, immune system disease, psychotic disorder, alcohol dependence and nicotine dependence comprising administering to a patient in need of said treatment a therapeutically effective amount of a compound of formula (I) according to claim 2.
18. A method of treatment of appetite disorder, gastrointestinal disorder, inflammatory phenomena, immune system disease, psychotic disorder, alcohol dependence and nicotine dependence comprising administering to a patient in need of said treatment a therapeutically effective amount of a compound of formula (I) according to claim 3.
19. A method of treatment of appetite disorder, gastrointestinal disorder, inflammatory phenomena, immune system disease, psychotic disorder, alcohol dependence and nicotine dependence comprising administering to a patient in need of said treatment a therapeutically effective amount of a compound of formula (I) according to claim 4.
20. A method of treatment of appetite disorder, gastrointestinal disorder, inflammatory phenomena, immune system disease, psychotic disorder, alcohol dependence and nicotine dependence comprising administering to a patient in need of said treatment a therapeutically effective amount of a compound of formula (I) according to claim 5.
21. A method of treatment of appetite disorder, gastrointestinal disorder, inflammatory phenomena, immune system disease, psychotic disorder, alcohol dependence and nicotine dependence comprising administering to a patient in need of said treatment a therapeutically effective amount of a compound of formula (I) according to claim 6.
22. A method of treatment of appetite disorder, gastrointestinal disorder, inflammatory phenomena, immune system disease, psychotic disorder, alcohol dependence and nicotine dependence comprising administering to a patient in need of said treatment a therapeutically effective amount of a compound of formula (I) according to claim 7.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. An apparatus for providing flushing fluid at different rates, said apparatus comprising;
a valve for controlling flow through a housing, said valve having a reset area to close the valve,
a first bleed valve for constantly providing high pressure fluid to said reset area through a first path,
a second bleed valve for providing high pressure fluid to said reset area through a second path,
an actuator having;
a first position in which fluid is prevented from escaping from said second path,
a second position in which fluid is allowed to escape from said second path and said second bleed valve is activated, and
a third position in which fluid is allowed to escape from said second path and said second bleed valve is activated,
wherein if said second bleed valve is activated, said first bleed valve causes said reset area to close said valve in a first time period and if said second bleed valve is not activated said first and second valves cause said reset area to close said valve in a second time period wherein said second time period is less than said first time period.
2. The apparatus of claim 1 wherein said second bleed valve comprises;
a slot having an inlet, a first outlet and a second outlet,
a first ball having a dimension to seal either of said first outlet or said second outlet,
a second ball having a dimension to seal said second outlet.
3. The apparatus of claim 2 wherein said slot has a dimension in which said second ball cannot pass said first ball therein.
4. The apparatus of claim 2 further comprising;
said second outlet having a first area having a first diameter and a second area having a second diameter,
a pin having a shaft disposed in said first area and a head disposed in said second area, said shaft cooperating with said actuator and,
a channel in fluid communication with said second area.
5. The apparatus of claim 2 wherein said actuator contacts said pin if said actuator is in said third position.
6. The apparatus of claim 5 wherein said actuator has a plunger.
7. The apparatus of claim 4 wherein said pin has a length such that said pin cannot escape said first area and said second area.
8. The apparatus of claim 1 wherein said valve comprises;
a pressure cup disposed in said reset area, said pressure cup including a closed body in which a piston translates.
9. The apparatus of claim 8 in which said piston controls flow from said reset area into said second path.
10. The apparatus of claim 1 in which said second path allows fluid to drain from said reset area to open said valve.
11. The apparatus of claim 10 in which said fluid that drains escapes through said actuator.
12. The apparatus of claim 1 wherein said actuator further comprises
a handle for manipulation,
a plunger engaging said handle,
a sleeve having a bore for receiving said plunger and a contour which said handle engages if manipulated, said plunger traveling a first distance if said handle engages said first portion of said contour and a second distance if engaging a second portion of said contour.
13. The apparatus of claim 12 wherein said handle further comprises a flange for engaging said contour and said plunger.
14. A method for providing flushing fluid at different rates, said method comprising;
controlling flow through a housing by using a valve having a reset area to close the valve,
providing high pressure fluid to said reset area through a first path,
providing high pressure fluid through a bleed valve to said reset area through a second path,
maintaining said valve in a static position if an actuator is in a first position in which fluid is prevented from escaping from said second path,
opening said valve by placing said actuator in a second position in which fluid is allowed to escape from said second path and said bleed valve is not activated, or
opening said valve by placing said actuator in a third position in which fluid is allowed to escape from said second path and said bleed valve is activated,
wherein if said bleed valve is activated, said high pressure fluid passing through said first path causes said reset area to close said valve in a first time period and if said bleed valve is not activated said first and second paths cause said reset area to close said valve in a second time period wherein said second time period is less than said first time period.
15. The method of claim 14 wherein said method further comprises
providing a second bleed valve having a slot having an inlet, a first outlet and a second outlet,
providing first sealing mechanism,
providing a second sealing mechanism,
sealing said first outlet with said first sealing mechanism if said actuator activates said bleed valve wherein said high pressure fluid is provided through said second path to said reset area.
16. The method of claim 14 wherein said method further comprises
providing a second bleed valve having a slot having an inlet, a first outlet and a second outlet,
providing first ball,
providing a second ball,
sealing said first outlet with said second ball and
sealing said second outlet with said first ball if said actuator activates said bleed valve.
17. The method of claim 16 further comprising;
sealing said first outlet with said second ball.
18. The method of claim 17 further comprising;
providing said first outlet having a first area having a first diameter and a second area having a second diameter, a pin having a shaft disposed in said first area and a head disposed in said second area, said shaft cooperating with said actuator and a channel in fluid communication with said second area and
contacting said pin with said actuator to deactivate said bleed valve.
19. The method of claim 14 further comprising controlling flow from said second path into said reset area.
20. The method of claim 14 further comprising draining fluid from said reset area through said second path.
21. The method of claim 20 further comprising draining fluid from said reset area through said actuator.
22. A bleed valve, said bleed valve comprising;
a slot having an inlet, a first outlet and a second outlet,
a first ball having a dimension to seal either of said first outlet or said second outlet,
a second ball having a dimension to seal said second outlet.
23. The apparatus of claim 22 wherein said slot has a dimension in which said second ball cannot pass said first ball therein.
24. The apparatus of claim 22 further comprising;
said second outlet having a first area having a first diameter and a second area having a second diameter,
a pin having a shaft disposed in said first area and a head disposed in said second area, said shaft cooperating with said actuator and,
a channel in fluid communication with said second area.
25. The apparatus of claim 24 wherein said pin has a length such that said pin cannot escape said first area and said second area.