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US 6,670,398 B2Granted
Compounds and methods for treating transplant rejection
AssigneeAtheroGenics, Inc.
InventorsDavid B. Edwards, Patricia K. Somers, Mitchell Glass
Life of this patent
Estimating the term…
Abstract
The use of compounds of the formula and pharmaceutically acceptable salts thereof, alone or in combination for the treatment of transplant rejection, wherein the substituents are further defined in the application.
Claims25
A method for treating transplant rejection in a mammal comprising administering to said mammal an effective amount of a compound of formula
- or a pharmaceutically acceptable salt thereof wherein:
- Y is a bond or
- R1, R2, R3, and R4 are independently selected from the group consisting of hydrogen, hydroxy, C1-10alkyl, aryl, heteroaryl, C1-10alkaryl, and aryl C1-10alkyl, wherein all nonhydrogen and hydroxy substituents may optionally be substituted from one or more of the group selected from C1-10alkyl, halogen, nitro, amino, halo1-10alkyl, C1-10alkylamino, diC1-10alkylamino, acyl, and acyloxy;
- Z is selected from the group consisting of C1-10alkyl, C2-10alkenyl, C2-10alkynyl, hydroxyC1-10alkyl, aryl, heteroaryl, C1-10alkaryl, arylC1-10alkyl, heteroarylC1-10alkyl, C1-10alkoxyC1-10alkyl, C1-10alkylaminoC1-10alkyl, carboxyC1-10alkyl, C1-10dialkylaminoC1-10alkyl, aminoC1-10alkyl, heterocycle, heterocyclC1-10alkyl, R7NH, R7R7N, carboxy, carbohydrate group, carbohydrate lactone group, and an alditol group wherein all may optionally be substituted by one or more R5;
- R5 is independently selected from the group selected from hydroxy, C1-10alkyl, C1-10alkoxy, halo, nitro, amino, cyano, C1-10alkylamino, diC1-10alkylamino, acyl, acyloxy, COOH, COOR7, OC(O)R7, CH(OH)R7, NHR7, NR7R7, C(O)NH2, C(O)NHR7, CONR7R7, NHC(O)O—R7, OSO3H, SO3H, SO2NHR7, SO2NR7R7, P(O)(OH)OR7, PO2H2P(O)(OH)R7, P(O)(OR7)2, P(O)R7(OR7), OPO3H, PO3H2, hydroxymethyl, and cyclic phosphate, wherein when possible, all may be optionally substituted by one or more R6;
- R6 is independently selected from the group consisting of hydroxy, C1-10alkyl, C1-10alkoxy, acyloxy, halo, nitro, amino, cyano, haloC1-10alkyl, C1-10alkylamino, diC1-10alkylamino, acyl, and acyloxy;
- R7 is independently selected from the group consisting of C1-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxy, C1-10alkoxycarbonylC1-10alkyl, aryl, carboxyC1-10alkyl, C1-10alkylcarboxyC1-10alkyl, C1-10alkylcarboxyC1-10aryl, heterocycle, heterocyclC1-10alkyl, and heteroaryl, wherein all may be optionally substituted by one or more R8;
- and
- R8 is independently selected from the group consisting of hydroxy, C1-10alkyl, C1-10alkoxy, acyloxy, halo, nitro, amino, cyano, and carboxy;
- wherein two R7 groups may come together to form a 4 to 7 membered ring.
7 more elements
A method for treating transplant rejection in a mammal comprising administering to said mammal an effective amount of a compound of formula
- or a pharmaceutically acceptable salt wherein:
- Y is a bond;
- Z is selected from the group consisting of C1-10alkyl, C2-10alkenyl, C2-10alkynyl, hydroxyC1-10alkyl, aryl, heteroaryl, C1-10alkaryl, arylC1-10alkyl, heteroarylC1-10alkyl, C1-10alkoxyC1-10alkyl, C1-10alkylaminoC1-10alkyl, carboxyC1-10alkyl, C1-10dialkylaminoC1-10alkyl, aminoC1-10alkyl, heterocycle, heterocyclC1-10alkyl, R7NH, R7R7N, carbohydrate group, carbohydrate lactone group, and an alditol group wherein all may optionally be substituted by one or more R5;
- R5 is independently selected from the group selected from hydroxy, C1-10alkyl, C1-10alkoxy, halo, nitro, amino, cyano, C1-10alkylamino, diC1-10alkylamino, acyl, acyloxy, COOH, COOR7, OC(O)R7, CH(OH)R7, NHR7, NR7R7, C(O)NH2, C(O)NHR7, CONR7R7, NHC(O)O—R7, OSO3H, SO3H, SO2NHR7, SO2NR7R7, P(O)(OH)OR7, PO2H2 P(O)(OH)R7, P(O)(OR7)2, P(O)R7(OR7), OPO3H, PO3H2, hydroxymethyl, and cyclic phosphate, wherein when possible, all may be optionally substituted by one or more R6;
- R6 is independently selected from the group consisting of hydroxy, C1-10alkyl, C1-10alkoxy, acyloxy, halo, nitro, amino, cyano, haloC1-10alkyl, C1-10alkylamino, diC1-10alkylamino, acyl, and acyloxy;
- R7 is independently selected from the group consisting of C1-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxy, C1-10alkoxycarbonylC1-10alkyl, aryl, carboxyC1-10alkyl, C1-10alkylcarboxyC1-10alkyl, C1-10alkylcarboxyC1-10aryl, heterocycle, heterocyclC1-10alkyl, and heteroaryl, wherein all may be optionally substituted by one or more R8;
- and
- R8 is independently selected from the group consisting of hydroxy, C1-10alkyl, C1-10alkoxy, acyloxy, halo, nitro, amino, cyano, and carboxy;
- wherein two R7 groups may come together to form a 4 to 7 membered ring.
6 more elements
A method for treating transplant rejection in a mammal comprising administering to said mammal an effective amount of a compound of formula
- or a pharmaceutically acceptable salt wherein:
- Z is selected from the group consisting of C1-10alkyl, C2-10alkenyl, C2-10alkynyl, hydroxyC1-10alkyl, aryl, heteroaryl, C1-10alkaryl, aryl1-10alkyl, heteroarylC1-10alkyl, C1-10alkoxyC1-10alkyl, C1-10alkylaminoC1-10alkyl, carboxyC1-10alkyl, C1-10dialkylaminoC1-10alkyl, aminoC1-10alkyl, heterocycle, heterocyclC1-10alkyl, R7NH, R7R7N, carboxy, carbohydrate group, carbohydrate lactone group, and an alditol group wherein all may optionally be substituted by one or more R5;
- R5 is independently selected from the group selected from hydroxy, C1-10alkyl, C1-10alkoxy, halo, nitro, amino, cyano, C1-10alkylamino, diC1-10alkylamino, acyl, acyloxy, COOH, COOR7, OC(O)R7, CH(OH)R7, NHR7, NR7R7, C(O)NH2, C(O)NHR7, CONR7R7, NHC(O)O—R7, OSO3H, SO3H, SO2NHR7, SO2NR7R7, P(O)(OH)OR7, PO2H2P(O)(OH)R7, P(O)(OR7)2, P(O)R7(OR7), OPO3H, PO3H2, hydroxymethyl, and cyclic phosphate, wherein when possible, all may be optionally substituted by one or more R6;
- R6 is independently selected from the group consisting of hydroxy, C1-10alkyl, C1-10alkoxy, acyloxy, halo, nitro, amino, cyano, haloC1-10alkyl, C1-10alkylamino, diC1-10alkylamino, acyl, and acyloxy;
- R7 is independently selected from the group consisting of C1-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxy, C1-10alkoxycarbonylC1-10alkyl, aryl, carboxyC1-10alkyl, C1-10alkylcarboxyC1-10alkyl, C1-10alkylcarboxyC1-10aryl, heterocycle, heterocyclC1-10alkyl, and heteroaryl, wherein all may be optionally substituted by one or more R8;
- and
- R8 is independently selected from the group consisting of hydroxy, C1-10alkyl, C1-10alkoxy, acyloxy, halo, nitro, amino, cyano, and carboxy;
- wherein two R7 groups may come together to form a 4 to 7 membered ring.
5 more elements
A compound of the formula
- or its pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.