A3 adenosine receptor antagonists and partial agonists

A compound of Formula I:

• wherein
• R1 is selected from the group consisting of C3-C8 cycloalkyl C1-C6 alkyl, C3-C8 dicycloalkyl C1-C6 alkyl, C7-C12 bicycloalkyl C1-C6 alkyl, C7-C14 tricycloalkyl C1-C6 alkyl, C6-C14 aryl, C6-C14 aryl C1-C6 alkyl, C6-C14 diaryl C1-C6 alkyl, C6-C14 aryl C1-C6 alkoxy, C1-C6 alkyl carbonyl, sulfonyl, C1-C6 alkyl sulfonyl, C6-C14 aryl sulfonyl, heterocyclyl C1-C6 alkyl, heterocyclyl, heteroaryl C1-C6 alkyl, 4-[[[4-[[[(2-amino C1-C6 alkyl)amino]-carbonyl]-C1-C6 alkyl]anilino]carbonyl]C1-C6 alkyl]C6-C14 aryl, and C6-C14 aryl C3-C8 cycloalkyl, wherein the aryl or heterocyclyl portion of R1 is optionally substituted with one or more substituents selected from the group consisting of halo, amino, hydroxyl, carboxy, C1-C6 alkoxycarbonyl, C1-C6 alkylaminocarbonyl, C1-C6 dialkyl aminocarbonyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C6-C14 aryloxy, hydroxy C1-C6 alkyl, hydroxy C2-C6 alkenyl, hydroxy C2-C6 alkynyl, carboxy C1-C6 alkyl, carboxy C2-C6 alkenyl, carboxy C2-C6 alkynyl, aminocarbonyl C1-C6 alkyl, aminocarbonyl C2-C6 alkenyl, aminocarbonyl C2-C6 alkynyl, and C≡C—(CH2)n—COR7 wherein R7 is selected from the group consisting of OH, OR8, and NR9R10, wherein R8 is selected from the group consisting of C1-C6 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl C1-C6 alkyl, C3-C8 dicycloalkyl C1-C6 alkyl, C7-C12 bicycloalkyl C1-C6 alkyl, C7-C14 tricycloalkyl C1-C6 alkyl, C6-C14 aryl, C6-C14 aryl C1-C6 alkyl, C6-C14 diaryl C1-C6 alkyl;
• and R9 and R10 are independently selected from the group consisting of hydrogen, C1-C6 alkyl, and (CH2)nR11 wherein R11 is NR12R13, wherein R12 and R13 are independently selected from the group consisting of hydrogen, C1-C6 alkyl, and COR14 wherein R14 is hydrogen or C1-C6 alkyl;
• wherein n is an integer from 1 to 10;
• and the cycloalkyl portion of R1 is optionally substituted with one or more substituents selected from the group consisting of halo, amino, C1-C6 alkyl, C1-C6 alkoxy, C6-C14 aryloxy, C1-C6 hydroxyalkyl, C2-C6 hydroxyalkenyl, C2-C6 hydroxy alkynyl, aminocarbonyl C1-C6 alkoxy, and C6-C14 aryl C1-C6 alkoxy;
• R2 is selected from the group consisting of hydrogen, halo, amino, hydrazido, mercapto, C1-C20 alkylamino, C6-C14 aryl amino, C6-C14 aryloxy, C1-C20 alkyl, C1-C20 alkoxy, C1-C20 alkylthio, pyridylthio, C7-C12 cycloalkyl C1-C20 alkyl, C7-C12 bicycloalkyl C1-C20 alkyl, C7-C12 bicycloalkenyl C1-C20 alkyl, C6-C14 aryl C1-C20 alkyl, C2-C20 alkenyl, C7-C12 cycloalkyl C2-C20 alkenyl, C7-C12 bicycloalkyl C2-C20 alkenyl, C7-C12 bicycloalkenyl C2-C20 alkenyl, C6-C14 aryl C2-C20 alkenyl, C2-C20 alkynyl, carboxy alkyl C2-C20 alkynyl, —C≡C—(CH2)m—C(═O)—O—C1-C6 alkyl, —C≡C—(CH2)m—C(═O)—NH—(CH2)n—NH2, —C≡C—(CH2)m—C1-C6 alkyl, —C≡C—(CH2)m-aryl, wherein m and n are independently 1 to 10, C7-C12 cycloalkyl C2-C20 alkynyl, C7-C12 bicycloalkyl C2-C20 alkynyl, C7-C12 bicycloalkenyl C2-C20 alkynyl, C6-C14 aryl C2-C20 alkynyl, and the alkyl, cycloalkyl, or aryl portion of R2 is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, amino, alkylamino, dialkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkyl aminocarbonyl, aminoalkyl aminocarbonyl, and trialkylsilyl;
• R3 and R4 are independently selected from the group consisting of hydroxyl, amino, mercapto, ureido, C1-C6 alkyl carbonylamino, hydroxy C1-C6 alkyl, and hydrazinyl;
• and
• R5 is selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, heteroaryl, and C1-C6 aminoalkyl;
• or a pharmaceutically acceptable salt thereof.