US 2006/0040996 A1Published application

Benzothiazole-and benzoxazole-4, 7-dione derivatives and their use as dcd25 phosphatase inhibitors

AssigneeSociete de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S.)

InventorsMarie-Odile Galcera Contour, Olivier Lavergne, Marrie-Christine Brezak Pannetier, Gregoire Prevost

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Abstract

The invention concerns the use as cdc25 phosphatase inhibitors, in particular cdc25-C phosphatase, and CD45 phosphatase, of compounds of general formula (I), wherein: W represents O or S. In accordance with the invention, the compounds of general formula (I) can in particular be used for preparing a medicine for cancer treatment.

Claims14

Dependent claims

A method of inhibiting at least one activity selected from the group consisting of phosphatases cdc 25 and phosphatase CD 45 in a warm-blooded animals comprising administering to a warm-blooded animal in need thereof an inhibiting amount of a compound of the formula

wherein
R1 is selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, alkylthioalkyl, cycloalkyl, —(CH2)—X—Y, —(CH2)-Z-NR5R6—CHR35R36, R35 and R36 form together with the carbon atom which carries them an indanyl or tetralinyl, or R35 and R36 form together with the carbon atom which carries them a saturated heterocycle of 5 to 7 ring members and 1 to 2 heteroatoms selected from the group consisting of O, N and S, the nitrogen atoms of said heterocycle being optionally substituted by alkyl or benzyl,
R1 also being able, when W is O, to represent carbocyclic aryl optionally substituted 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl and alkoxy,
X is a bond or alkylene of 1 to 5 carbon atoms,
Y is a saturated carbon-containing cyclic system containing 1 to 3 condensed rings selected individually from rings with 3 to 7 members, or Y is a saturated heterocycle containing 1 to 2 heteroatoms individually selected from the group consisting of O, N and S and attached to X radical by N or CH, said saturated heterocycle moreover containing 2 to 6 additional members independently selected from the group consisting of —CHR7—, —CO—, —NR8—, —O— and —S—, R7 is hydrogen or alkyl and R8 is selected from the group consisting of hydrogen, alkyl and aralkyl, or Y is a carbocyclic or heterocyclic aryl optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, a haloalkoxy, hydroxy, nitro, cyano, phenyl, —SO2NHR9 and —NR10R11, R9 is selected from the group consisting of hydrogen, alkyl and phenyl, and R10 and R11 are independently alkyl,
Z is a bond or alkylene of 1 to 5 carbon atoms,
R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, aralkyl and —(CH2)n—OH, n is an integer from 1 to 6,
or R5 is selected from the group consisting of alkoxycarbonyl, haloalkoxycarbonyl of and aralkoxycarbonyl and R6 is hydrogen or a methyl,
or R5 and R6 form together with the nitrogen atom a heterocycle of 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being independently selected from the group consisting of —CR12R13—, —O—, —S— and —NR14, R12 and R13 are independently each time that they occur hydrogen or alkyl, and R14 is selected from the group consisting of hydrogen, alkyl and aralkyl, or R14 is phenyl optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl and alkoxy,
R2 is hydrogen, alkyl and aralkyl;
or R1 and R2 form together with the nitrogen atom a heterocycle with 4 to 8 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being at least one member selected from the group consisting of —CR15R16—, —O—, —S— and —NR17—, R15 and R16 are independently each time that they occur a hydrogen or alkyl, and R17 is selected from the group consisting of hydrogen, alkyl and aralkyl;
R3 is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy and alkylthio;
R4 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, cyano, amino, —CH2—COOR18, —CH2—CO—NR19R20 and —CH2—NR21R22, or R4 is a carbocyclic or heterocyclic aryl optionally substituted from 1 to 4 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy and NR37R38, or R4 is phenyl possessing two substituents which form together a methylenedioxy or ethylenedioxy,
R18 is hydrogen or alkyl,
R19 is selected from the group consisting of hydrogen, alkyl and aralkyl, the aryl of which is optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, nitro, cyano, phenyl, —SO2NHR23 and —NR24R25, R23 is selected from the group consisting of hydrogen, alkyl and phenyl, and R24 and R25 are independently alkyl, R20 is hydrogen or alkyl,
or R19 and R20 form together with the nitrogen atom a heterocycle with 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle at least one member selected from the group consisting of —CR26R27—, —O—, —S— and —NR28—, R26 and R27 are independently each time that they occur a selected from the group consisting of hydrogen or alkyl, and R28 is selected from the group consisting of hydrogen, alkyl and aralkyl, or R28 is phenyl optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl alkoxy,
R21 is selected from the group consisting of hydrogen, alkyl and aralkyl, the aryl group of which is optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, nitro, cyano, phenyl, —SO2NHR29 and —NR30R31, R29 is selected from the group consisting of hydrogen, alkyl and phenyl, and R30 and R31 are independently alkyl,
R22 is hydrogen or alkyl,
or R21 and R22 form together with the nitrogen atom a heterocycle with 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being independently selected from the group consisting of —CR32R33—, —O—, —S— and —NR34—, R32 and R33 are independently each time that they occur hydrogen or alkyl, and R34 is hydrogen, alkyl and aralkyl, or R34 is phenyl optionally substituted from 1 to 3 times by substituents independently selected from the group consisting of halogen, alkyl and alkoxy, R37 and R38 are independently hydrogen or alkyl or R37 and R38 form together with the nitrogen atom a heterocycle with 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being at least one member selected from the group consisting of —CR39R40—, —O—, —S— and —NR41—, R39 and R40 are independently each time that they occur hydrogen or alkyl, and R41 is hydrogen or alkyl;
and
W is O or S;
or a pharmaceutically acceptable salt.

19 more elements

A pharmaceutical composition for inhibiting phosphatases cd25 and/or phosphatase CD45 comprising an inhibitorily effective amount of a compound of the formula

wherein R1 is selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, alkylthioalkyl, cycloalkyl, —(CH2)—X—Y, —(CH2)-Z-NR5R6 and —CHR35R36, R35 and R36 form together with the carbon atom which carries them indanyl or tetralinyl, or R35 and R36 form together with the carbon atom which carries them a saturated heterocycle containing 5 to 7 ring members and 1 to 2 heteroatoms selected from the group consisting of O, N and S, the nitrogen atoms of said heterocycle being optionally substituted by alkyl or benzyl,
R1 also being able, when W is O, to represent carbocyclic aryl optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl and alkoxy,
X is a bond or alkylene of 1 to 5 carbon atoms,
Y is a saturated carbon-containing cyclic system containing 1 to 3 condensed rings selected independently from rings with 3 to 7 members, or Y is saturated heterocycle containing 1 to 2 heteroatoms chosen independently from O, N and S and attached to X by an N or CH member, said saturated heterocycle moreover containing 2 to 6 additional members selected from the group consisting of —CHR7—, —CO—, —NR8—, —O— and —S—, R7 is hydrogen or alkyl and R8 is selected from the group consisting of hydrogen, alkyl and aralkyl, or Y is a carbocyclic or heterocyclic aryl optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl, a haloalkyl, alkoxy, haloalkoxy, hydroxy, nitro, cyano, phenyl, SO2NHR9 and NR10R11, R9 is hydrogen or alkyl or phenyl, and R10 and R11 are independently alkyl,
Z is a bond or alkylene of 1 to 5 carbon atoms,
R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, aralkyl or —(CH2)n—OH in which n is an integer from 1 to 6,
or R5 is selected from the group consisting of alkoxycarbonyl, haloalkoxycarbonyl and aralkoxycarbonyl and R6 is hydrogen or a methyl,
or R5 and R6 form together with the nitrogen atom a heterocycle with 4 to 7 ng members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being independently selected from the group consisting of —CR12R13—, —O—, —S— and —NR14—, R12 and R13 are independently each time that they occur hydrogen or alkyl, and R14 is hydrogen, alkyl and aralkyl, or R14 is phenyl optionally substituted from 1 to 3 times by a at least one member selected from the group consisting of halogen, alkyl and alkoxy,
R2 is selected from the group consisting of hydrogen, alkyl and aralkyl;
or R1 and R2 form together with the nitrogen atom a heterocycle with 4 to 8 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being at least one member selected from the group consisting of —CR15R16—, —O—, —S— and —NR17—, R15 and R16 are independently each time that they occur a hydrogen or alkyl, and R17 is selected from the group consisting of hydrogen, alkyl and aralkyl;
R3 is selected from the group consisting of hydrogen, a halogen, alkyl, haloalkyl, alkoxy and alkylthio;
R4 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, cyano, amino, —CH2—COOR18, —CH2—CO—NR19R20 and —CH2—NR21R22, or R4 is a carbocyclic or heterocyclic aryl optionally substituted from 1 to 4 times by at least one member selected from a halogen, alkyl, haloalkyl, alkoxy, haloalkoxy and NR37R38, or R4 is phenyl possessing two substituents which form together a methylenedioxy or ethylenedioxy,
R18 is hydrogen or alkyl,
R19 is selected from the group consisting of hydrogen, alkyl and aralkyl, the aryl group of which is optionally substituted from 1 to 3 times at least one member selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, nitro, cyano, phenyl, —SO2NHR23 and —NR24R25, R23 is selected from the group consisting of hydrogen, alkyl and phenyl, and R24 and R25 are independently alkyl, R20 is hydrogen or alkyl,
or R19 and R20 form together with the nitrogen atom a heterocycle with 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being independently selected from the group consisting of —CR26R27—, —O—, —S— and —NR28—, R26 and R27 are independently each time that they occur hydrogen or alkyl, and R28 is selected from the group consisting of hydrogen, alkyl and aralkyl,
or R28 is phenyl optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl and alkoxy,
R21 is selected from the group consisting of hydrogen, alkyl and aralkyl the aryl group of which is optionally substituted from 1 to 3 times by selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, nitro, cyano, phenyl, —SO2NHR29 and —NR30R31, R29 is selected from the group consisting of hydrogen, alkyl and phenyl, and R30 and R31 are independently alkyl,
R22 is hydrogen or alkyl,
or R21 and R22 form together with the nitrogen atom a heterocycle with 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being at least one member selected from the group consisting of —CR32R33—, —O—, —S— and —NR34—, R32 and R33 are independently each time that they occur hydrogen or alkyl, and R34 is hydrogen, alkyl and aralkyl, or R34 is phenyl optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl alkoxy,
R37 and R38 are independently hydrogen or alkyl or R37 and R38 form together with the nitrogen atom a heterocycle with 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being at least one member selected from the group consisting of —CR39R40—, —O—, —S— and —NR41—, R39 and R40 are independently each time that they occur hydrogen or alkyl, and R41 is hydrogen or alkyl;
and
W is O or S;
it being understood that if W is S and R4 is optionally substituted aryl, then R1 is selected from the group consisting of alkoxyalkyl, alkylthioalkyl, cycloalkyl, —(CH2)—X—Y and —(CH2)-Z-NR5R6;
or a pharmaceutically acceptable salt thereof and a pharmaceutical carrier.

21 more elements

A compound of the formula

wherein:
R1 is selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, alkylthioalkyl, cycloalkyl, —(CH2)—X—Y, —(CH2)-Z-NR5R6 and —CHR35R36, R35 and R36 form together with the carbon atom which carries them indanyl or tetralinyl, or R35 and R36 form together with the carbon atom which carries them a saturated heterocycle of 5 to 7 ring members and 1 to 2 heteroatoms selected from the group consisting of O, N and S, nitrogen atoms of said heterocycle being optionally substituted by alkyl or benzyl,
R1 also being able, when W is O, to represent a carbocyclic aryl optionally substituted from 1 to 3 times by selected from the group consisting of halogen, alkyl, haloalkyl and alkoxy,
X is a bond or alkylene of 1 to 5 carbon atoms,
Y is a saturated carbon-containing cyclic system containing 1 to 3 condensed rings chosen independently from rings with 3 to 7 members, or Y is a saturated heterocycle containing 1 to 2 heteroatoms selected from the group consisting of O, N and S and attached to X by a N or CH member, said saturated heterocycle containing 2 to 6 additional members of at least one member selected from the group consisting of —CHR7—, —CO—, —NR8—, —O— and —S—, R7 is hydrogen or alkyl and R8 is selected from the group consisting of hydrogen, alkyl and aralkyl, or Y is a carbocyclic or heterocyclic aryl optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, nitro, cyano, phenyl, —SO2NHR9 and —NR10R11, R9 is selected from the group consisting of hydrogen, alkyl and phenyl, and R10 and R11 are independently alkyl,
Z is a bond or alkylene of 1 to 5 carbon atoms,
R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, aralkyl and —(CH2)n—OH radical in which n represents an integer from 1 to 6,
or R5 is selected from the group consisting of alkoxycarbonyl, haloalkoxycarbonyl and aralkoxycarbonyl and R6 is hydrogen or a methyl,
or R5 and R6 form together with the nitrogen atom a heterocycle with 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being independently selected from the group consisting of —CR12R13—, —O—, —S— and —NR14—, R12 and R13 are independently each time that they occur hydrogen or alkyl, and R14 is selected from the group consisting of hydrogen, alkyl and aralkyl, or R14 is phenyl optionally substituted from 1 to 3 times by at least one member selected from the croup consisting of halogen, alkyl and alkoxy,
R2 is selected from the group consisting of hydrogen, alkyl and aralkyl;
or R1 and R2 form together with the nitrogen atom a heterocycle with 4 to 8 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being independently selected from the group consisting of —CR15R16—, —O—, —S— and —NR17—, R15 and R16 are independently each time that they occur a hydrogen or alkyl, and R17 is hydrogen or alkyl or aralkyl;
R3 is selected from the group consisting of hydrogen, a halogen, alkyl, haloalkyl, alkoxy and alkylthio;
R4 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, cyano, amino, —CH2—COOR18, —CH2—CO—NR19R20 and —CH2—NR21R22, or R4 is a carbocyclic or heterocyclic aryl optionally substituted from 1 to 4 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy and —NR37R38, or R4 is phenyl possessing two substituents which form together a methylenedioxy or ethylenedioxy, R18 is hydrogen or alkyl,
R19 is selected from the group consisting of hydrogen, alkyl and aralkyl the aryl of which is optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl, a haloalkyl, alkoxy, haloalkoxy, hydroxy, nitro, cyano, phenyl, —SO2NHR23 and —NR24R25, R23 is selected from the group consisting of hydrogen, alkyl and phenyl, and R24 and R25 are independently alkyl, R20 is hydrogen or alkyl,
or R19 and R20 form together with the nitrogen atom a heterocycle with 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being independently selected from the group consisting of —CR26R27—, —O—, —S— and —NR28—, R26 and R27 are independently each time that they occur a hydrogen or alkyl, and R28 is selected from the group consisting of hydrogen, alkyl and aralkyl,
or R28 is phenyl optionally substituted from 1 to 3 times by at least one member selected from the group consisting of hydrogen, alkyl and alkoxy,
R21 is at least one member selected from the group consisting of hydrogen, alkyl and aralkyl the aryl of which is optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, nitro, cyano, phenyl, —SO2NHR29 and —NR30R31, R29 is selected from the group consisting of hydrogen:
alkyl and phenyl, and R30 and R31 are independently alkyl,
R22 is hydrogen or alkyl,
or R21 and R22 form together with the nitrogen atom a heterocycle with 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being independently selected from the group consisting of —CR32R33—, —O—, —S— and —NR34—, R32 and R33 are independently each time they occur a hydrogen or alkyl, and R34 is selected from the group consisting of hydrogen, alkyl and aralkyl, or R34 is phenyl optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl and alkoxy,
R37 and R38 are independently hydrogen or alkyl or R37 and R38 form together with the nitrogen atom a heterocycle with 4 to 7 ring members comprising from 1 to 2 heteroatoms, the members necessary for completing the heterocycle being independently selected from the group consisting of —CR39R40—, —O—, —S— and —NR41—, R39 and R40 are independently each time that they occur hydrogen or alkyl, and R41 is hydrogen or alkyl;
and
W is O or S;
it being understood that:
if W is S and R4 is alkyl, then R1 is not hydrogen or alkyl or cycloalkyl and/or R3 is hydrogen or alkyl,
if W is S and R4 is optionally substituted aryl, then R1 is selected from the group consisting of alkoxyalkyl, alkylthioalkyl, cycloalkyl, —(CH2)—X—Y and —(CH2)-Z-NR5R6;
or a salt thereof.

24 more elements

A compound of claim 11, selected from the grout consisting of:

-2-methyl-5-{[2-(4-morpholinyl)ethyl]amino}-1,3-benzothiazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-methyl-1,3-benzothiazole-4,7-dione;
-5-{[6-(dimethylamino)hexyl]amino}-2-methyl-1,3-benzothiazole-4,7-dione;
-5-{[3-(dimethylamino)-2,2-dimethylpropyl]amino}-2-methyl-1,3-benzothiazole-4,7-dione;
-2-methyl-5-{[3-(4-methyl-1-piperazinyl)propyl]amino}-1,3-benzothiazole-4,7-dione;
-5-[(1-ethylhexyl)amino]-2-methyl-1,3-benzothiazole-4,7-dione;
-5-[(1-adamantylmethyl)amino]-2-methyl-1,3-benzothiazole-4,7-dione;
-2-methyl-5-[(2-thienylmethyl)amino]-1,3-benzothiazole-4,7-dione;
-5-[(3-chlorobenzyl)amino]-2-methyl-1,3-benzothiazole-4,7-dione;
-2-methyl-5-[(4-pyridinylmethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-methyl-5-(propylamino)-1,3-benzothiazole-4,7-dione;
-5-{[3-(1H-imidazol-1-yl)propyl]amino}-2-methyl-1,3-benzothiazole-4,7-dione;
-4-{2-[(2-methyl-4,7-dioxo-4,7-dihydro-1,3-benzothiazol-5-yl)amino]ethyl}-benzenesulphonamide;
-5-(4-benzyl-1-piperazinyl)-2-methyl-1,3-benzothiazole-4,7-dione;
-5-[(2-methoxyethyl)amino]-2-methyl-1,3-benzothiazole-4,7-dione;
-2-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-methyl-5-[(2-piperidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-5-{[2-(diisopropylamino)ethyl]amino}-2-methyl-1,3-benzothiazole-4,7-dione;
-5-[(1-benzylpyrrolidin-3-yl)amino]-2-methyl-1,3-benzothiazole-4,7-dione;
-5-{[3-(dimethylamino)propyl]amino}-2-methyl-1,3-benzothiazole-4,7-dione;
-2-methyl-5-{[2-(1-methylpyrrolidin-2-yl)ethyl]amino}-1,3-benzothiazole-4,7-dione;
-2-methyl-5-{[3-(2-methylpiperidin-1-yl)propyl]amino}-1,3-benzothiazole-4,7-dione;
-5-{[4-(dimethylamino)butyl]amino}-2-methyl-1,3-benzothiazole-4,7-dione;
-5-{[5-(dimethylamino)pentyl]amino}-2-methyl-1,3-benzothiazole-4,7-dione;
-5-(2,3-dihydro-1H-inden-1-ylamino)-2-methyl-1,3-benzothiazole-4,7-dione;
-5-{benzyl[2-(dimethylamino)ethyl]amino}-2-methyl-1,3-benzothiazole-4,7-dione;
tert-butyl methyl {3-[(2-methyl-4,7-dioxo-4,7-dihydro-1,3-benzothiazol-5-yl)amino]-propyl}carbamate;
tert-butyl 3-[(2-methyl-4,7-dioxo-4,7-dihydro-1,3-benzothiazol-5-yl)amino]propylcarbamate;
-2-methyl-5-{[3-(methylamino)propyl]amino}-1,3-benzothiazole-4,7-dione;
-5-[(3-aminopropyl)amino]-2-methyl-1,3-benzothiazole-4,7-dione;
-6-chloro-5-{[2-(dimethylamino)ethyl]amino}-2-methyl-1,3-benzothiazole-4,7-dione;
-6-bromo-5-{[2-(dimethylamino)ethyl]amino}-2-methyl-1,3-benzothiazole-4,7-dione;
-6-(butylthio)-5-{[2-(dimethylamino)ethyl]amino}-2-methyl-1,3-benzothiazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-(morpholin-4-ylmethyl)-1,3-benzothiazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-[(4-phenylpiperazin-1-yl)methyl]-1,3-benzothiazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-(piperidin-1-ylmethyl)-1,3-benzothiazole-4,7-dione;
-5-{[6-(dimethylamino)hexyl]amino}-2-ethyl-1,3-benzoxazole-4,7-dione;
-6-{[6-(dimethylamino)hexyl]amino}-2-ethyl-1,3-benzoxazole-4,7-dione;
2-ethyl-5-(4-methylpiperazin-1-yl)-1,3-benzoxazole-4,7-dione;
2-ethyl-6-(4-methylpiperazin-1-yl)-1,3-benzoxazole-4,7-dione;
-2-ethyl-5-[(1-ethylhexyl)amino]-1,3-benzoxazole-4,7-dione;
-2-ethyl-6-[(1-ethylhexyl)amino]-1,3-benzoxazole-4,7-dione;
-5-azocan-1-yl-2-ethyl-1,3-benzoxazole-4,7-dione;
-6-azocan-1-yl-2-ethyl-1,3-benzoxazole-4,7-dione;
-2-ethyl-5-morpholin-4-yl-1,3-benzoxazole-4,7-dione;
-2-ethyl-6-morpholin-4-yl-1,3-benzoxazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-ethyl-6-methyl-1,3-benzoxazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-phenyl-1,3-benzoxazole-4,7-dione;
-6-{[2-(dimethylamino)ethyl]amino}-2-phenyl-1,3-benzoxazole-4,7-dione;
-5-{[6-(dimethylamino)hexyl]amino}-2-phenyl-1,3-benzoxazole-4,7-dione;
-6-{[6-(dimethylamino)hexyl]amino}-2-phenyl-1,3-benzoxazole-4,7-dione;
-2-(2,6-difluorophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(2,6-difluorophenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-[4-(diethylamino)phenyl]-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-[4-(diethylamino)phenyl]-6-{[2-(dimethylamino)ethyl]-amino}-1,3-benzoxazole-4,7-dione;
-2-[4-(diethylamino)phenyl]-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-[4-(diethylamino)phenyl]-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(4-chlorophenyl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(4-chlorophenyl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(4-chlorophenyl)-5-{[3-(dimethylamino)propyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(4-chlorophenyl)-6-{[3-(dimethylamino)propyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(4-chlorophenyl)-5-{[4-(dimethylamino)butyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(4-chlorophenyl)-6-{([4-(dimethylamino)butyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2-fluorophenyl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2-fluorophenyl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2-fluorophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(2-fluorophenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(2-bromophenyl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2-bromophenyl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2-bromophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(2-bromophenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(2-bromophenyl)-5-{[3-(dimethylamino)propyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2-bromophenyl)-6-{[3-(dimethylamino)propyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2-chlorophenyl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2-chlorophenyl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2-chlorophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(2-chlorophenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(3-bromophenyl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(3-bromophenyl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(4-bromophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(4-bromophenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(4-bromophenyl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(4-bromophenyl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(4-fluorophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(4-fluorophenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-(4-fluorophenyl)-1,3-benzoxazole-4,7-dione;
-6-{[2-(dimethylamino)ethyl]amino}-2-(4-fluorophenyl)-1,3-benzoxazole-4,7-dione;
-5-[(1-benzylpyrrolidin-3-yl)amino]-2-(4-fluorophenyl)-1,3-benzoxazole-4,7-dione;
-6-[(1-benzylpyrrolidin-3-yl)amino]-2-(4-fluorophenyl)-1,3-benzoxazole-4,7-dione;
-5-{[3-(dimethylamino)propyl]amino}-2-(4-fluorophenyl)-1,3-benzoxazole-4,7-dione;
-6-{[3-(dimethylamino)propyl]amino}-2-(4-fluorophenyl)-1,3-benzoxazole-4,7-dione;
-2-(3,5-difluorophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(3,5-difluorophenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(3,5-difluorophenyl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(3,5-difluorophenyl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2,5-difluorophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(2,5-difluorophenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(2,5-difluorophenyl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2,5-difluorophenyl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2,3-difluorophenyl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2,3-difluorophenyl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2,3-difluorophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(2,3-difluorophenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(2,3-difluorophenyl)-5-{[3-(dimethylamino)propyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2,3-difluorophenyl)-6-{[3-(dimethylamino)propyl]amino-1,3-benzoxazole-4,7-dione;
-5-[(2-pyrrolidin-1-ylethyl)amino]-2-(3,4,5-trifluorophenyl)-1,3-benzoxazole-4,7-dione;
-6-[(2-pyrrolidin-1-ylethyl)amino]-2-(3,4,5-trifluorophenyl)-1,3-benzoxazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-(3,4,5-trifluorophenyl)-1,3-benzoxazole-4,7-dione;
-6-{[2-(dimethylamino)ethyl]amino}-2-(3,4,5-trifluorophenyl)-1,3-benzoxazole-4,7-dione;
-5-[(2-pyrrolidin-1-ylethyl)amino]-2-(2,3,4,5-tetrafluorophenyl)-1,3-benzoxazole-4,7-dione;
-6-[(2-pyrrolidin-1-ylethyl)amino]-2-(2,3,4,5-tetrafluorophenyl)-1,3-benzoxazole-4,7-dione;
-5-1 [2-(dimethylamino)ethyl]amino}-2-(2,3,4,5-tetrafluorophenyl)-1,3-benzoxazole-4,7-dione;
-6-{([2-(dimethylamino)ethyl]amino}-2-(2,3,4,5-tetrafluorophenyl)-1,3-benzoxazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-[2-fluoro-6-(trifluoromethyl)phenyl]-1,3-benzoxazole-4,7-dione;
-6-{[2-(dimethylamino)ethyl]amino}-2-[2-fluoro-6-(trifluoromethyl)phenyl]-1,3-benzoxazole-4,7-dione;
-2-[2-fluoro-6-(trifluoromethyl)phenyl]-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-[2-fluoro-6-(trifluoromethyl)phenyl]-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-5-{[3-(dimethylamino)propyl]amino}-2-[2-fluoro-6-(trifluoromethyl)phenyl]-1,3-benzoxazole-4,7-dione;
-6-{[3-(dimethylamino)propyl]amino}-2-[2-fluoro-6-(trifluoromethyl)phenyl]-1,3-benzoxazole-4,7-dione;
-2-[2-chloro-5-(trifluoromethyl)phenyl]-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-[2-chloro-5-(trifluoromethyl)phenyl]-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-[2-chloro-5-(trifluoromethyl)phenyl]-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-[2-chloro-5-(trifluoromethyl)phenyl]-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-[2-chloro-5-(trifluoromethyl)phenyl]-5-{[3-(dimethylamino)propyl]amino}-1,3-benzoxazole-4,7-dione;
-2-[2-chloro-5-(trifluoromethyl)phenyl]-6-{[3-(dimethylamino)propyl]amino}-1,3-benzoxazole-4,7-dione;
-2-[2-chloro-6-fluorophenyl]-5-{[3-(dimethyl amino)propyl]amino 1-1,3-benzoxazole-4,7-dione;
-2-[2-chloro-6-fluorophenyl]-6-{[3-(dimethylamino)propyl]amino}-1,3-benzoxazole-4,7-dione;
-2-[2-chloro-6-fluorophenyl]-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-[2-chloro-6-fluorophenyl]-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-[3,4-dimethoxyphenyl]-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-[3,4-dimethoxyphenyl]-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-[2-bromo-3-pyridyl]-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-[2-bromo-3-pyridyl]-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-cyclohexyl-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-cyclohexyl-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-cyclohexyl-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-cyclohexyl-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-5-[(2-pyrrolidin-1-ylethyl)amino]-2-thien-2-yl-1,3-benzothiazole-4,7-dione;
-6-[(2-pyrrolidin-1-ylethyl)amino]-2-thien-2-yl-1,3-benzothiazole-4,7-dione;
-2-(2,5-dichlorothien-3-yl)-5-{([2-(dimethylamino)ethyl]amino}-1,3-benzothiazole-4,7-dione;
-2-(2,5-dichlorothien-3-yl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzothiazole-4,7-dione;
-2-(2,5-dichlorothien-3-yl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-(2,5-dichlorothien-3-yl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-(2-furyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-(2-furyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-(2-methoxyphenyl)-1,3-benzothiazole-4,7-dione;
-6-{[2-(dimethylamino)ethyl]amino}-2-(2-methoxyphenyl)-1,3-benzothiazole-4,7-dione;
-5-([2-(dimethylamino)ethyl]amino}-2-(2-fluorophenyl)-1,3-benzothiazole-4,7-dione;
-6-{[2-(dimethylamino)ethyl]amino}-2-(2-fluorophenyl)-1,3-benzothiazole-4,7-dione;
-2-(2-fluorophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-(2-fluorophenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-(4-fluorophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-(4-fluorophenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-(4-fluorophenyl)-1,3-benzothiazole-4,7-dione;
-6-{[2-(dimethylamino)ethyl]amino}-2-(4-fluorophenyl)-1,3-benzothiazole-4,7-dione;
-2-(2,6-difluorophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-(2,6-difluorophenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-(2,6-difluorophenyl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzothiazole-4,7-dione;
-2-(2,6-difluorophenyl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzothiazole-4,7-dione;
-5-[[2-(dimethylamino)ethyl](ethyl)amino]-2-methyl-1,3-benzothiazole-4,7-dione;
-5-[[2-(dimethylamino)ethyl](methyl)amino]-2-methyl-1,3-benzothiazole-4,7-dione;
-2-[2,6-dichloro-5-fluoro-3-pyridyl]-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-[2,6-dichloro-5-fluoro-3-pyridyl]-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-[2,6-dichloro-5-fluoro-3-pyridyl]-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-[2,6-dichloro-5-fluoro-3-pyridyl]-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(2,4-difluorophenyl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(2,4-difluorophenyl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-5-{[2-(dimethylamino)etbyl]amino}-2-(2,3,4-trifluorophenyl)-1,3-benzoxazole-4,7-dione;
-6-{[2-(dimethylamino)ethyl]amino}-2-(2,3,4-trifluorophenyl)-1,3-benzoxazole-4,7-dione;
-5-[(2-pyrrolidin-1-ylethyl)amino]-2-(2,3,4-trifluorophenyl)-1,3-benzoxazole-4,7-dione;
-6-[(2-pyrrolidin-1-ylethyl)amino]-2-(2,3,4-trifluorophenyl)-1,3-benzoxazole-4,7-dione;
-2-(3-fluoro-4-methylphenyl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(3-fluoro-4-methylphenyl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(3-fluoro-4-methylphenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(3-fluoro-4-methylphenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(4-chlorophenyl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzothiazole-4,7-dione;
-2-(4-chlorophenyl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzothiazole-4,7-dione;
-2-(4-chlorophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-2-(4-chlorophenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-(2,3,4,5-tetrafluorophenyl)-1,3-benzothiazole-4,7-dione;
-6-{[2-(dimethylamino)ethyl]amino}-2-(2,3,4,5-tetrafluorophenyl)-1,3-benzothiazole-4,7-dione;
-5-{([2-(dimethylamino)ethyl]amino}-2-(3,4,5-trifluorophenyl)-1,3-benzothiazole-4,7-dione;
-6-{[2-(dimethylamino)ethyl]amino}-2-(3,4,5-trifluorophenyl)-1,3-benzothiazole-4,7-dione;
-5-[(2-pyrrolidin-1-ylethyl)amino]-2-(2,4,6-trifluorophenyl)-1,3-benzothiazole-4,7-dione;
-6-[(2-pyrrolidin-1-ylethyl)amino]-2-(2,4,6-trifluorophenyl)-1,3-benzothiazole-4,7-dione;
-2-(1,3-benzodioxol-5-yl)-5-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-2-(1,3-benzodioxol-5-yl)-6-{[2-(dimethylamino)ethyl]amino}-1,3-benzoxazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-(4-ethylphenyl)-1,3-benzoxazole-4,7-dione;
-6-{[2-(dimethylamino)ethyl]amino}-2-(4-ethylphenyl)-1,3-benzoxazole-4,7-dione;
-2-(4-ethylphenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-2-(4-ethylphenyl)-6-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzoxazole-4,7-dione;
-5-{[2-(dimethylamino)ethyl]amino}-2-(2-fluoro-6-methoxyphenyl)-1,3-benzoxazole-4,7-dione;
-6-{[2-(dimethylamino)ethyl]amino}-2-(2-fluoro-6-methoxyphenyl)-1,3-benzoxazole-4,7-dione;
or of a salt thereof.

191 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/500,411Filed 24 Dec 2002
Priority: FR 01/1688927 Dec 2001
Published: 23 Feb 2006
Term ends: Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07D 263/56
Benzoxazoles; Hydrogenated benzoxazoles: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
A61K 31/428
Thiazoles: condensed with carbocyclic rings
A61K 31/4439
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/454
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone

Family

US 7,279,467 B2Related patent
US 2006/0040996 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

wherein
R1 is selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, alkylthioalkyl, cycloalkyl, —(CH2)—X—Y, —(CH2)-Z-NR5R6—CHR35R36, R35 and R36 form together with the carbon atom which carries them an indanyl or tetralinyl, or R35 and R36 form together with the carbon atom which carries them a saturated heterocycle of 5 to 7 ring members and 1 to 2 heteroatoms selected from the group consisting of O, N and S, the nitrogen atoms of said heterocycle being optionally substituted by alkyl or benzyl,
R1 also being able, when W is O, to represent carbocyclic aryl optionally substituted 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl and alkoxy,
X is a bond or alkylene of 1 to 5 carbon atoms,
Y is a saturated carbon-containing cyclic system containing 1 to 3 condensed rings selected individually from rings with 3 to 7 members, or Y is a saturated heterocycle containing 1 to 2 heteroatoms individually selected from the group consisting of O, N and S and attached to X radical by N or CH, said saturated heterocycle moreover containing 2 to 6 additional members independently selected from the group consisting of —CHR7—, —CO—, —NR8—, —O— and —S—, R7 is hydrogen or alkyl and R8 is selected from the group consisting of hydrogen, alkyl and aralkyl, or Y is a carbocyclic or heterocyclic aryl optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, a haloalkoxy, hydroxy, nitro, cyano, phenyl, —SO2NHR9 and —NR10R11, R9 is selected from the group consisting of hydrogen, alkyl and phenyl, and R10 and R11 are independently alkyl,
Z is a bond or alkylene of 1 to 5 carbon atoms,
R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, aralkyl and —(CH2)n—OH, n is an integer from 1 to 6,
or R5 is selected from the group consisting of alkoxycarbonyl, haloalkoxycarbonyl of and aralkoxycarbonyl and R6 is hydrogen or a methyl,
or R5 and R6 form together with the nitrogen atom a heterocycle of 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being independently selected from the group consisting of —CR12R13—, —O—, —S— and —NR14, R12 and R13 are independently each time that they occur hydrogen or alkyl, and R14 is selected from the group consisting of hydrogen, alkyl and aralkyl, or R14 is phenyl optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl and alkoxy,
R2 is hydrogen, alkyl and aralkyl;
or R1 and R2 form together with the nitrogen atom a heterocycle with 4 to 8 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being at least one member selected from the group consisting of —CR15R16—, —O—, —S— and —NR17—, R15 and R16 are independently each time that they occur a hydrogen or alkyl, and R17 is selected from the group consisting of hydrogen, alkyl and aralkyl;
R3 is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy and alkylthio;
R4 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, cyano, amino, —CH2—COOR18, —CH2—CO—NR19R20 and —CH2—NR21R22, or R4 is a carbocyclic or heterocyclic aryl optionally substituted from 1 to 4 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy and NR37R38, or R4 is phenyl possessing two substituents which form together a methylenedioxy or ethylenedioxy,
R18 is hydrogen or alkyl,
R19 is selected from the group consisting of hydrogen, alkyl and aralkyl, the aryl of which is optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, nitro, cyano, phenyl, —SO2NHR23 and —NR24R25, R23 is selected from the group consisting of hydrogen, alkyl and phenyl, and R24 and R25 are independently alkyl, R20 is hydrogen or alkyl,
or R19 and R20 form together with the nitrogen atom a heterocycle with 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle at least one member selected from the group consisting of —CR26R27—, —O—, —S— and —NR28—, R26 and R27 are independently each time that they occur a selected from the group consisting of hydrogen or alkyl, and R28 is selected from the group consisting of hydrogen, alkyl and aralkyl, or R28 is phenyl optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl alkoxy,
R21 is selected from the group consisting of hydrogen, alkyl and aralkyl, the aryl group of which is optionally substituted from 1 to 3 times by at least one member selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, nitro, cyano, phenyl, —SO2NHR29 and —NR30R31, R29 is selected from the group consisting of hydrogen, alkyl and phenyl, and R30 and R31 are independently alkyl,
R22 is hydrogen or alkyl,
or R21 and R22 form together with the nitrogen atom a heterocycle with 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being independently selected from the group consisting of —CR32R33—, —O—, —S— and —NR34—, R32 and R33 are independently each time that they occur hydrogen or alkyl, and R34 is hydrogen, alkyl and aralkyl, or R34 is phenyl optionally substituted from 1 to 3 times by substituents independently selected from the group consisting of halogen, alkyl and alkoxy, R37 and R38 are independently hydrogen or alkyl or R37 and R38 form together with the nitrogen atom a heterocycle with 4 to 7 ring members comprising 1 to 2 heteroatoms, the members necessary for completing the heterocycle being at least one member selected from the group consisting of —CR39R40—, —O—, —S— and —NR41—, R39 and R40 are independently each time that they occur hydrogen or alkyl, and R41 is hydrogen or alkyl;
and
W is O or S;
or a pharmaceutically acceptable salt.

19 more elements

Facts

Application

10/500,411Filed 24 Dec 2002

Priority

FR 01/1688927 Dec 2001

Published

23 Feb 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07D 263/56
Benzoxazoles; Hydrogenated benzoxazoles: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
A61K 31/428
Thiazoles: condensed with carbocyclic rings
A61K 31/4439
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/454
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone