Back to results
US 2003/0195208 A1Published application
Phthalimido derivatives and a process for their preparation
AssigneeHoffmann-La Roche Inc.
InventorsAndrea Cesura, Rosa Maria Rodriguez Sarmiento, Andrew William Thomas, Rene Wyler
Life of this patent
Estimating the term…
Abstract
This invention relates to phthalimido derivatives of the formula 1 wherein X is —N═ or —CH═, and R1 to R4 and m are as defined in the specification, as well as their pharmaceutically acceptable salts. The invention further relates to pharmaceutical compositions containing these compounds, a method of treating a disease by administering a therapeutically effective amount of at least one of these compounds, and a process for their preparation for the treatment or prevention of diseases in which MAO-B inhibitors might be beneficial.
Claims20
A compound of the formula
- 14
- wherein
- X is —N═ or —CH═;
- R1 is —CO—NR5R6;
- —CHR7—(CH2)n—CO—NR5R6;
- —(CH2)n—NR5R6;
- —(CH2)n—COOR8;
- —(CH2)n—CN;
- —CHR7—(CH2)n—CF3;
- —(CH2)n—NH—COR9;
- —(CH2)n—NH—COOR8;
- a heterocyclic ring-containing group selected from —(CH2)n-piperidinyl,
- (CH2)n-morpholinyl, —(CH2)n-tetrahydrofuranyl;
- —(CH2)n-thiophenyl or —(CH2)n-isoxazolyl, wherein the heterocyclic ring may be substituted by C1-C6-alkyl;
- a phenyl;
- —(CH2)n-phenyl, wherein the phenyl ring may be substituted by halogen or halogen-(C1-C6)-alkyl;
- —(CH2)p—OR8;
- —(CH2)p—SR8;
- —(CH2)p—SO—R9;
- or
- —(CH2)n—CS—NR5R6;
- R2 is hydrogen;
- C1-C6-alkyl;
- —(CH2)p—OR10;
- —(CH2)p—SR10;
- or benzyl;
- R3 is hydrogen or C1-C6-alkyl;
- R4 is halogen, halogen-(C1-C6)-alkyl, cyano, C1-C6-alkoxy or halogen-(C1-C6)-alkoxy;
- R5 and R6 are independently from each other hydrogen or C1-C6-alkyl;
- R7 is hydrogen, hydroxy or C1-C6-alkoxy;
- R8 is hydrogen or C1-C6-alkyl;
- R9 is C1-C6-alkyl;
- R10 is hydrogen or C1-C6-alkyl;
- m is 1, 2 or 3;
- n is 0, 1 or 2;
- and
- p is 1 or 2;
- or a pharmaceutically acceptable salt thereof.
35 more elements
A method of treating or preventing a disease mediated by monoamine oxidase B inhibitors comprising administering to a patient in need of such treatment a therapeutically effective amount of at least one compound of the formula
- 15
- wherein
- X is —N=or —CH═;
- R1 is —CO—NR5R6;
- —CHR7—(CH2)n—CO—NR5R6;
- —(CH2)n—NR5R6;
- —(CH2)n—COOR8;
- —(CH2)n—CN;
- —CHR7—(CH2)n—CF3;
- —(CH2)n—NH—COR9;
- —(CH2)n—NH—COOR8;
- a heterocyclic ring-containing group selected from —(CH2)n-piperidinyl,
- —(CH2)n-morpholinyl, —(CH2)n-tetrahydrofuranyl;
- —(CH2)n-thiophenyl or —(CH2)n-isoxazolyl, wherein the heterocyclic ring may be substituted by C1-C6-alkyl;
- a phenyl;
- —(CH2)n-phenyl, wherein the phenyl ring may be substituted by halogen or halogen-(C1-C6)-alkyl;
- —(CH2)p—OR8;
- —(CH2)p—SR8;
- —(CH2)p—SO—R9;
- or
- —(CH2)n—CS—NR5R6;
- R2 is hydrogen;
- C1-C6-alkyl;
- —(CH2)p—OR10;
- —(CH2)p—SR10;
- or benzyl;
- R3 is hydrogen or C1-C6-alkyl;
- R4 is halogen, halogen-(C1-C6)-alkyl, cyano, C1-C6-alkoxy or halogen-(C1-C6)-alkoxy;
- R5 and R6 are independently from each other hydrogen or C1-C6-alkyl;
- R7 is hydrogen, hydroxy or C1-C6-alkoxy;
- R8 is hydrogen or C1-C6-alkyl;
- R9 is C1-C6-alkyl;
- R10 is hydrogen or C1-C6-alkyl;
- m is 1, 2 or 3;
- n is 0, 1 or 2;
- and
- p is 1 or 2;
- or a pharmaceutically acceptable salt thereof.
35 more elements
A process for the manufacture of a compound of formula I
- 16
- wherein
- X is —N═ or —CH═;
- R1 is —CO—NR5R6;
- —CHR7—(CH2)n—CO—NR5R6;
- —(CH2)n—NR5R6;
- —(CH2)n—COOR8;
- —(CH2)n—CN;
- —CHR7—(CH2)n—CF3;
- —(CH2)n—NH—COR9;
- —(CH2)n—NH—COOR8;
- a heterocyclic ring-containing group selected from —(CH2)n-piperidinyl,
- —(CH2)n-morpholinyl, —(CH2)n-tetrahydrofuranyl;
- —(CH2)n-thiophenyl or —(CH2)n-isoxazoly, wherein the heterocyclic ring may be substituted by C1-C6-alkyl;
- a phenyl;
- —(CH2)n-phenyl, wherein the phenyl ring may be substituted by halogen or halogen-(C1-C6)-alkyl;
- —(CH2)p—OR8;
- —(CH2)p—SR8;
- —(CH2)p—SO—R9;
- or
- —(CH2)n—CS—NR5R6;
- R2 is hydrogen;
- C1-C6-alkyl;
- —(CH2)p—OR10;
- —(CH2)p—SR10;
- or benzyl;
- R3 is hydrogen or C1-C6-alkyl;
- R4 is halogen, halogen-(C1-C6)-alkyl, cyano, C1-C6-alkoxy or halogen-(C1-C6)-alkoxy;
- R5 and R6 are independently from each other hydrogen or C1-C6-alkyl;
- R7 is hydrogen, hydroxy or C1-C6-alkoxy;
- R8 is hydrogen or C1-C6-alkyl;
- R9 is C1-C6-alkyl;
- R10 is hydrogen or C1-C6-alkyl;
- m is 1, 2 or 3;
- n is 0, 1 or 2;
- and
- p is 1 or 2;
- which process comprises
- a) reacting a compound of formula
- 17
- with a compound of formula
- 18
39 more elements
A process for the manufacture of a compound of formula I
- 19
- wherein
- X is —N═ or —CH═;
- R1 is —CO—NR5R6;
- —CHR7—(CH2)n—CO—NR5R6;
- —(CH2)n—NR5R6;
- —(CH2)n—COOR8;
- —(CH2)n—CN;
- —CHR7—(CH2)n—CF3;
- —(CH2)n—NH—COR9;
- —(CH2)n—NH—COOR8;
- a heterocyclic ring-containing group selected from —(CH2)n-piperidinyl,
- —(CH2)n-morpholinyl, —(CH2)n-tetrahydrofuranyl;
- —(CH2)n-thiophenyl or —(CH2)n-isoxazolyl, wherein the heterocyclic ring may be substituted by C1-C6-alkyl;
- a phenyl;
- —(CH2)n-phenyl, wherein the phenyl ring may be substituted by halogen or halogen-(C1-C6)-alkyl;
- —(CH2)p—OR8;
- —(CH2)p—SR8;
- —(CH2)p—SO—R9;
- or
- —(CH2)n—CS—NR5R6;
- R2 is hydrogen;
- C1-C6-alkyl;
- —(CH2)p—OR10;
- —(CH2)p—SR10;
- or benzyl;
- R3 is hydrogen or C1-C6-alkyl;
- R4 is halogen, halogen-(C1-C6)-alkyl, cyano, C1-C6-alkoxy or halogen-(C1-C6)-alkoxy;
- R5 and R6 are independently from each other hydrogen or C1-C6-alkyl;
- R7 is hydrogen, hydroxy or C1-C6-alkoxy;
- R8 is hydrogen or C1-C6-alkyl;
- R9 is C1-C6-alkyl;
- R10 is hydrogen or C1-C6-alkyl;
- m is 1, 2 or 3;
- n is 0, 1 or 2;
- and
- p is 1 or 2;
- which process comprises reacting a compound of formula
- 20
- with a compound of formula
- 21
38 more elements
A pharmaceutical composition containing one or more compounds of the formula
- 22
- wherein
- X is —N═ or —CH═;
- R1 is —CO—NR5R6;
- —CHR7—(CH2)n—CO—NR5R6;
- —(CH2)n—NR5R6;
- —(CH2)n—COOR8;
- —(CH2)n—CN;
- —CHR7—(CH2)n—CF3;
- —(CH2)n—NH—COR9;
- —(CH2)n—NH—COOR8;
- a heterocyclic ring-containing group selected from —(CH2)n-piperidinyl,
- —(CH2)n-morpholinyl, —(CH2)n-tetrahydrofuranyl;
- —(CH2)n-thiophenyl or —(CH2)n-isoxazolyl, wherein the heterocyclic ring may be substituted by C1-C6-alkyl;
- a phenyl;
- —(CH2)n-phenyl, wherein the phenyl ring may be substituted by halogen or halogen-(C1-C6)-alkyl;
- —(CH2)p—OR8;
- —(CH2)p—SR8;
- —(CH2)p—SO—R9;
- or
- —(CH2)n—CS—NR5R6;
- R2 is hydrogen;
- C1-C6-alkyl;
- —(CH2)p—OR10;
- —(CH2)p—SR10;
- or benzyl;
- R3 is hydrogen or C1-C6-alkyl;
- R4 is halogen, halogen-(C1-C6)-alkyl, cyano, C1-C6-alkoxy or halogen-(C1-C6)-alkoxy;
- R5 and R6 are independently from each other hydrogen or C1-C6-alkyl;
- R7 is hydrogen, hydroxy or C1-C6-alkoxy;
- R8 is hydrogen or C1-C6-alkyl;
- R9 is C1-C6-alkyl;
- R10 is hydrogen or C1-C6-alkyl;
- m is 1, 2 or 3;
- n is 0, 1 or 2;
- and
- p is 1 or 2;
- or a pharmaceutically acceptable salt thereof, and pharmaceutically acceptable excipients.
35 more elements
Dependencies are inferred from the claim text.