Adenosine receptor antagonists and methods of making and using the same

A compound comprising the formula:

• or a pharmaceutically acceptable addition salt thereof;
• wherein R1 and R2 are independently selected from the group consisting of:
• a) hydrogen;
• b) alkyl, alkenyl of not less than 3 carbons, or alkynyl of not less than 3 carbons;
• wherein said alkyl, alkenyl, or alkynyl is either unsubstituted or substituted with one or more substituents selected from the group consisting of hydroxy, alkoxy, amino, alkylamino, dialkylamino, heterocyclyl, acylamino, alkylsulfonylamino, and heterocyclylcarbonylamino;
• and
• c) aryl or substituted aryl;
• R3 is a bicyclic, tricyclic or pentacyclic group selected from the group consisting of:
• wherein the bicyclic or tricyclic group is either unsubstituted or substituted with one or more substituenits selected from the group consisting of:
• (a) alkyl, alkenyl, and alkynyl;
• wherein each alkyl, alkenyl, or alkynyl group is either unsubstituted or functionalized with one or more substituents selected from the group consisting of (amino)(R5)acylhydrazinylcarbonyl, (amino)(R5)acyloxycarboxy, (hydroxy)(carboalkoxy)alkylcarbamoyl, acyloxy, aldehyde, alkenylsulfonylamino, alkoxy, alkoxycarbonyl, alkylaminoalkylamino, alkylphosphono, alkylsulfonylamino, carbamoyl, R5, R5-alkoxy, cyano, cyanoalkylcarbamoyl, cycloalkylamino, dialkylamino, dialkylaminoalkylamino, dialkylphosphono, haloalkylsulfonylamino, (heterocyclylalkyl)amino, heterocyclylcarbamoyl, hydroxy, hydroxyalkylsulfonylamino, oximino, phosphono, substituted aralkylamino, substituted arylcarboxyalkoxycarbonyl, substituted heteroarylsulfonylamino, substituted heterocyclyl, thiocarbamoyl, and trifluoromethyl;
• and
• (b) (alkoxycarbonyl)aralkylcarbamoyl, aldehydo, alkenoxy, alkenylsulfonylamino, alkoxy, alkoxycarbonyl, alkylcarbamoyl, alkoxycarbonylamino, alkylsulfonylamino, alkylsulfonyloxy, amino, aminoalkylaralkylcarbamoyl, aminoalkylcarbamoyl, aminoalkylheterocyclylalkylcarbamoyl, aminocycloalkylalkylcycloalkylcarbamoyl, aminocycloalkylcarbamoyl, aralkoxycarbonylamino, arylheterocyclyl, aryloxy, arylsulfonylamino, arylsulfonyloxy, carbamoyl, —R5, R5-alkoxy, R5-alkyl(alkyl)amino, R5-alkylalkylcarbamoyl, R5-alkylcarbamoyl, R5-alkylsulfonyl, R5-alkylsulfonylamino, R5-alkylthio, R5-heterocyclylcarbonyl, cyano, cycloalkylamino, dialkylaminoalkylcarbamoyl, halogen, heterocyclyl, (heterocyclylalkyl)amino, hydroxy, oximino, substituted aralkylamino, substituted heterocyclyl, substituted heterocyclylsulfonylamino, sulfoxyacylamino, and thiocarbamoyl;
• R4 is selected from the group consisting of hydrogen, C1-4-alkyl, C1-4-alkyl-CO2H, and phenyl, wherein the C1-4-alkyl, C1-4-alkyl-CO2H, and phenyl groups are either unsubstituted or substituted with one to three substituents selected from the group consisting of halogen, —OH, —OMe, —NH2, NO2, benzyl, and benzyl substituted with one to three substituents selected from the group consisting of halogen, —OH, —OMe, —NH2, and —NO2;
• R5 is selected from the group consisting of —CH2COOH, —C(CF3)2OH, —CONHNHSO2CF3, —CONHOR4, —CONHSO2R4, —CONHSO2NHR4, —C(OH)R4PO3H2, —NHCOCF3, —NHCONHSO2R4, —NHPO3H2, —NHSO2R4, —NHSO2NHCOR4, —OPO3H2, —OSO3H, —PO(OH)R4, —PO3H2, —SO3H, —SO2NHR4, and the following:
• X1 and X2 are independently selected from the group consisting of O and S;
• Z is selected from the group consisting of a single bond, —O—, —(CH2)1-3—, —O(CH2)1-2—, —CH2OCH2—, —(CH2)1-2O—, —CH═CHCH2—, —CH═CH—, and —CH2CH═CH—;
• and
• R6 is selected from the group consisting of hydrogen, alkyl, acyl, alkylsulfonyl, aralkyl, substituted aralkyl, substituted alkyl, and heterocyclyl.