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US 2006/0135532 A1Published application
Platelet adenosine diphosphate receptor antagonists
AssigneeSchering Corporation
InventorsJudi Bryant, Brad Buckman, Imadul Islam, Raju Mohan, Michael Morrissey, Guo Ping Wei, Wei Xu, Shendong Yuan
Life of this patent
Estimating the term…
Abstract
Compounds of the following formula (I): where A, a, b, R1, R2, R3, R4 and R6 are described herein, are useful as inhibitors of platelet adenosine diphosphate. Pharmaceutical compositions containing these compounds, methods of using these compounds as antithrombotic agents and processes for synthesizing these compounds are also described herein.
Claims3
A compound of formula (I):
- wherein:
- a and b are independently 1 to 4;
- A is ═CH—;
- R1 is hydrogen, alkyl, carboxyalkyl, aryl, aralkyl, alkylcarbonyl, alkoxyalkoxyalkylcarbonyl, aryloxyalkylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, alkoxycarbonylalkyl, arylcarbonyl, cycloalkylcarbonyl, alkylsulfonyl, arylsulfonyl, heterocyclyl, or heterocyclylcarbonyl;
- R2 is hydrogen, alkyl, aryl, aralkyl, alkylsulfonylalkyl, aralkoxyalkyl, hydroxyalkyl, aminoalkyl, haloalkylsulfonylaminoalkyl, carboxyalkylthioalkyl, alkoxycarbonylalkylthioalkyl, carboxyalkyl, (carboxy)(hydroxy)alkyl, carboxyalkoxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, carboxyalkoxycarbonylalkyl, alkoxycarbonylalkoxycarbonylalkyl, aminocarbonylalkyl, aralkoxycarbonylaminoalkyl, alkoxycarbonylalkylaminocarbonylalkyl, carboxyalkylaminocarbonylalkyl, (alkoxycarbonylalkyl)(alkyl)aminocarbonylalkyl, (carboxyalkyl)(alkyl)aminocarbonylalkyl, tetrahydrofuranonyl, or heterocyclylalkyl;
- R3 is hydrogen, alkyl, hydroxy, halo, carboxyalkenyl, alkoxy, alkoxycarbonyl, alkoxycarbonylalkoxy, di(alkoxycarbonyl)alkoxy, carboxyalkoxy, di(carboxy)alkoxy, (carboxy)(hydroxy)alkoxy, (dialkylamino)(carboxy)alkoxy, hydroxyalkoxy, cyanoalkoxy, haloalkoxy, haloalkenyloxy, carboxyalkenyloxy, alkoxycarbonylalkenyloxy, (cycloalkyl)(alkoxycarbonyl)alkoxy, (cycloalkyl)(carboxy)alkoxy, alkylthio, carboxy, (dialkylaminocarbonylalkyl)(alkyl)amino, (carboxyalkyl)(alkyl)amino, (hydroxyalkyl)(alkyl)amino, (dialkylaminoalkyl)(alkyl)amino, carboxyalkylamino, mono(alkoxycarbonylalkyl)aminocarbonyl, mono(carboxyalkyl)aminocarbonyl, mono(di(alkoxycarbonyl)alkyl)aminocarbonyl, mono((alkoxycarbonyl)(carboxy)alkyl)aminocarbonyl, mono(dicarboxyalkyl)aminocarbonyl, aminocarbonylalkoxy, dialkylaminocarbonylalkoxy, monoaralkylaminocarbonylalkoxy, mono(carboxyalkyl)aminocarbonylalkoxy, mono(alkoxycarbonylalkyl)aminocarbonylalkoxy, carboxycycloalkoxy, alkoxycarbonylcycloalkoxy, aminocarbonylcycloalkoxy, heterocyclyl, tetrahydrofuranonyloxy, or heterocyclylalkoxy;
- each R4 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, aralkoxy, halo, haloalkyl, haloalkoxy, hydroxy, cyano, alkylthio, carboxy, alkoxycarbonyl, aminocarbonyl, alkylcarbonyl, nitro, amino, monoalkylamino, dialkylamino, carboxyalkylamino, alkylcarbonylamino, di(alkylcarbonyl)amino, hydroxyalkyl, dialkylaminoalkyl, carboxyalkoxy, alkoxycarbonylalkoxy, dialkylaminoalkoxy, and heterocyclylalkoxy;
- each R5 is independently selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, aralkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, carboxyalkyl, and alkoxycarbonylalkyl;
- R6 is —N(R7)—C(O)— or —C(O)—N(R7)—;
- R7 is hydrogen, alkyl, carboxyalkyl, or alkoxycarbonylalkyl;
- as a single stereoisomer, a mixture of individual stereoisomers, or a racemic mixture;
- or a pharmaceutically acceptable salt thereof.
9 more elements
A pharmaceutical composition useful in treating a mammal having a disease-state characterized by thrombotic activity, which composition comprises a pharmaceutically acceptable excipient and a compound of formula (I):
- wherein:
- a and b are independently 1 to 4;
- A is ═CH—;
- R1 is hydrogen, alkyl, carboxyalkyl, aryl, aralkyl, alkylcarbonyl, alkoxyalkoxyalkylcarbonyl, aryloxyalkylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, alkoxycarbonylalkyl, arylcarbonyl, cycloalkylcarbonyl, alkylsulfonyl, arylsulfonyl, heterocyclyl, or heterocyclylcarbonyl;
- R2 is hydrogen, alkyl, aryl, aralkyl, alkylsulfonylalkyl, aralkoxyalkyl, hydroxyalkyl, aminoalkyl, haloalkylsulfonylaminoalkyl, carboxyalkylthioalkyl, alkoxycarbonylalkylthioalkyl, carboxyalkyl, (carboxy)(hydroxy)alkyl, carboxyalkoxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, carboxyalkoxycarbonylalkyl, alkoxycarbonylalkoxycarbonylalkyl, aminocarbonylalkyl, aralkoxycarbonylaminoalkyl, alkoxycarbonylalkylaminocarbonylalkyl, carboxyalkylaminocarbonylalkyl, (alkoxycarbonylalkyl)(alkyl)aminocarbonylalkyl, (carboxyalkyl)(alkyl)aminocarbonylalkyl, tetrahydrofuranonyl, or heterocyclylalkyl;
- R3 is hydrogen, alkyl, hydroxy, halo, carboxyalkenyl, alkoxy, alkoxycarbonyl, alkoxycarbonylalkoxy, di(alkoxycarbonyl)alkoxy, carboxyalkoxy, di(carboxy)alkoxy, (carboxy)(hydroxy)alkoxy, (dialkylamino)(carboxy)alkoxy, hydroxyalkoxy, cyanoalkoxy, haloalkoxy, haloalkenyloxy, carboxyalkenyloxy, alkoxycarbonylalkenyloxy, (cycloalkyl)(alkoxycarbonyl)alkoxy, (cycloalkyl)(carboxy)alkoxy, alkylthio, carboxy, (dialkylaminocarbonylalkyl)(alkyl)amino, (carboxyalkyl)(alkyl)amino, (hydroxyalkyl)(alkyl)amino, (dialkylaminoalkyl)(alkyl)amino, carboxyalkylamino, mono(alkoxycarbonylalkyl)aminocarbonyl, mono(carboxyalkyl)aminocarbonyl, mono(di(alkoxycarbonyl)alkyl)aminocarbonyl, mono((alkoxycarbonyl)(carboxy)alkyl)aminocarbonyl, mono(dicarboxyalkyl)aminocarbonyl, aminocarbonylaikoxy, dialkylaminocarbonylalkoxy, monoaralkylaminocarbonylalkoxy, mono(carboxyalkyl)aminocarbonylalkoxy, mono(alkoxycarbonylalkyl)aminocarbonylalkoxy, carboxycycloalkoxy, alkoxycarbonylcycloalkoxy, aminocarbonylcycloalkoxy, heterocyclyl, tetrahydrofuranonyloxy, or heterocyclylalkoxy;
- each R4 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, aralkoxy, halo, haloalkyl, haloalkoxy, hydroxy, cyano, alkylthio, carboxy, alkoxycarbonyl, aminocarbonyl, alkylcarbonyl, nitro, amino, monoalkylamino, dialkylamino, carboxyalkylamino, alkylcarbonylamino, di(alkylcarbonyl)amino, hydroxyalkyl, dialkylaminoalkyl, carboxyalkoxy, alkoxycarbonylalkoxy, dialkylaminoalkoxy, or heterocyclylalkoxy;
- each R5 is independently selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, aralkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, carboxyalkyl, or alkoxycarbonylalkyl;
- R6 is —N(R7)—C(O)— or —C(O)—N(R7)—;
- R7 is hydrogen, alkyl, carboxyalkyl, or alkoxycarbonylalkyl;
- as a single stereoisomer, a mixture of individual stereoisomers, or a racemic mixture;
- or a pharmaceutically acceptable salt thereof.
9 more elements
A method of treating a disease-state characterized by thrombotic activity, which method comprises administering to a mammal having a disease-state characterized by thrombotic activity a therapeutically effective amount of a compound of formula (I):
- wherein:
- a and b are independently 1 to 4;
- A is ═CH—;
- R1 is hydrogen, alkyl, carboxyalkyl, aryl, aralkyl, alkylcarbonyl, alkoxyalkoxyalkylcarbonyl, aryloxyalkylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, alkoxycarbonylalkyl, arylcarbonyl, cycloalkylcarbonyl, alkylsulfonyl, arylsulfonyl, heterocyclyl, or heterocyclylcarbonyl;
- R2 is hydrogen, alkyl, aryl, aralkyl, alkylsulfonylalkyl, aralkoxyalkyl, hydroxyalkyl, aminoalkyl, haloalkylsulfonylaminoalkyl, carboxyalkylthioalkyl, alkoxycarbonylalkylthioalkyl, carboxyalkyl, (carboxy)(hydroxy)alkyl, carboxyalkoxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, carboxyalkoxycarbonylalkyl, alkoxycarbonylalkoxycarbonylalkyl, aminocarbonylalkyl, aralkoxycarbonylaminoalkyl, alkoxycarbonylalkylaminocarbonylalkyl, carboxyalkylaminocarbonylalkyl, (alkoxycarbonylalkyl)(alkyl)aminocarbonylalkyl, (carboxyalkyl)(alkyl)aminocarbonylalkyl, tetrahydrofuranonyl, or heterocyclylalkyl;
- R3 is hydrogen, alkyl, hydroxy, halo, carboxyalkenyl, alkoxy, alkoxycarbonyl, alkoxycarbonylalkoxy, di(alkoxycarbonyl)alkoxy, carboxyalkoxy, di(carboxy)alkoxy, (carboxy)(hydroxy)alkoxy, (dialkylamino)(carboxy)alkoxy, hydroxyalkoxy, cyanoalkoxy, haloalkoxy, haloalkenyloxy, carboxyalkenyloxy, alkoxycarbonylalkenyloxy, (cycloalkyl)(alkoxycarbonyl)alkoxy, (cycloalkyl)(carboxy)alkoxy, alkylthio, carboxy, (dialkylaminocarbonylalkyl)(alkyl)amino, (carboxyalkyl)(alkyl)amino, (hydroxyalkyl)(alkyl)amino, (dialkylaminoalkyl)(alkyl)amino, carboxyalkylamino, mono(alkoxycarbonylalkyl)aminocarbonyl, mono(carboxyalkyl)aminocarbonyl, mono(di(alkoxycarbonyl)alkyl)aminocarbonyl, mono((alkoxycarbonyl)(carboxy)alkyl)aminocarbonyl, mono(dicarboxyalkyl)aminocarbonyl, aminocarbonylalkoxy, dialkylaminocarbonylalkoxy, monoaralkylaminocarbonylalkoxy, mono(carboxyalkyl)aminocarbonylalkoxy, mono(alkoxycarbonylalkyl)aminocarbonylalkoxy, carboxycycloalkoxy, alkoxycarbonylcycloalkoxy, aminocarbonylcycloalkoxy, heterocyclyl, tetrahydrofuranonyloxy, or heterocyclylalkoxy;
- each R4 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, aralkoxy, halo, haloalkyl, haloalkoxy, hydroxy, cyano, alkylthio, carboxy, alkoxycarbonyl, aminocarbonyl, alkylcarbonyl, nitro, amino, monoalkylamino, dialkylamino, carboxyalkylamino, alkylcarbonylamino, di(alkylcarbonyl )amino, hydroxyalkyl, dialkylaminoalkyl, carboxyalkoxy, alkoxycarbonylalkoxy, dialkylaminoalkoxy, or heterocyclylalkoxy;
- each R5 is independently selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, aralkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, carboxyalkyl, or alkoxycarbonylalkyl;
- R6 is —N(R7)—C(O)— or —C(O)—N(R7)—;
- R7 is hydrogen, alkyl, carboxyalkyl, or alkoxycarbonylalkyl;
- as a single stereoisomer, a mixture of individual stereoisomers, or a racemic mixture;
- or a pharmaceutically acceptable salt thereof.
9 more elements
Dependencies are inferred from the claim text.