N-alkyl 2-(disubstituted)alkynyladenosine-5-uronamides as A₂A agonists

摘要

The present invention provides N-alkyl 2-(disubstituted)alkynyladenosine-5′-uronamides and derivatives thereof and pharmaceutical compositions containing the same that are selective agonists of A2A adenosine receptors (ARs). These compounds and compositions are useful as pharmaceutical agents.

主权项

1. A compound of Formula Ia or a stereoisomer or pharmaceutically acceptable salt thereof:wherein:
R is CH3; R1 is independently selected from: H, C1-8 alkyl, and C3-8 cycloalkyl; R2 is selected from: H, C1-8 alkyl-C3-8 cycloalkyl, C3-8cycloalkyl-C1-8 alkylene-, C1-8 alkoxy-C1-8 alkylene-, 5-10 membered heterocyclyl, 5-10 membered heterocyclyl-C1-8 alkylene-, 5-10 membered heteroaryl, 5-10 membered heteroaryl-C1-8 alkylene-, aryl, and aryl-C1-8 alkylene-; ring A is a phenyl ring or a 5-6 membered heteroaryl attached via the carbon atom shown and having 1-3 ring heteroatoms selected from O, N, and S(O)p; ring A is optionally substituted with 1-3 R3 groups; R3 is independently selected from: C1-8 alkyl, F, Cl, Br, I, —CN, ORa, SRa, NRaRb, CF3, OCF3, CORa, CO2Ra, C(O)NRaRb, OC(O)Ra, OCO2Ra, OC(O)NRaRb, NRbCORa, NRbCO2Ra, NRbC(O)NRaRb, S(O)pNRaRb, C3-10cycloalkyl, C3-10cycloalkyl-C1-8alkylene-, 5-10 membered heterocyclyl, 5-10 membered heterocyclyl-C1-8alkylene-, aryloxy, aryl, aryl-, -C1-8alkylene-, 5-10 membered heteroaryl, and 5-10 membered heteroaryl-C1-8alkylene-; Ra is independently selected from: H, C1-8 alkyl, C3-8cycloalkyl, and C3-8 C1-8 alkylene-; and, Rb is independently selected from: H, C1-8 alkyl, C3-8 cycloalkyl, and C3-8 cycloalkyl-C1-8 alkylene-.