Adenosine receptor antagonists and methods of making and using the same

A compound comprising the formula:

• or a pharmacologically acceptable addition salt thereof;
• wherein
• R1 and R2, independently, are selected from the group consisting of:
• a) hydrogen;
• b) alkyl, alkenyl of not less than 3 carbons, and alkynyl of not less than 3 carbons;
• wherein the alkyl, alkenyl, or alkynyl is either unsubstituted or substituted with one or two substituents selected from the group consisting of hydroxy, alkoxy, amino, alkylamino, dialkylamino, heterocyclyl, acylamino, alkylsulfonylamino, and heterocyclylcarbonylamino;
• and
• c) aryl and substituted aryl;
• R3 is a bicyclic or tricyclic group selected from the group consisting of:
• wherein the bicyclic or tricyclic group is either unsubstituted or substituted with one or more substituents selected from the group consisting of:
• (a) alkyl, alkenyl, and alkynyl;
• wherein the alkyl, alkenyl, and alkynyl are either unsubstituted or substituted with one or more substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkoxycarbonylaminoalkylamino, aralkoxycarbonyl, —R5, dialkylamino, (heterocyclylalkyl)amino, hydroxy, substituted arylsulfonylaminoalkylamino, and substituted heterocyclylaminoalkylamino;
• (b) acylaminoalkylamino, alkenylamino, alkoxycarbonyl, alkoxycarbonyl, alkoxycarbonylalkylamino, alkoxycarbonylaminoacyloxy, alkoxycarbonylaminoalkylamino, alkylamino, amino, aminoacyloxy, —R5, R5-alkoxy, dialkylaminoalkylamino, heterocyclyl, (heterocyclylalkyl)amino, hydroxy, substituted arylsulfonylaminoalkylamino, substituted heterocyclyl, and substituted heterocyclylaminoalkylamino;
• R4 is selected from the group consisting of —H, —C1-4-alkyl, —C1-4-alkyl-CO2H, and phenyl;
• wherein said —C1-4-alkyl, —C1-4-alkyl-CO2H, and phenyl are either unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, —OH, —OMe, —NH2, NO2 or benzyl, optionally substituted with one to three groups selected from 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, —SO3NHCOR4, —SO3NHCONHCO2R4, and:
• X1 and X2 are independently selected from 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, alkylsufonyl, aralkyl, substituted aralkyl, alkyl, and heterocyclyl.