Substituted bicyclic pyrimidine-based compounds and compositions and uses thereof

A compound of Formula I, or a pharmaceutically acceptable salt, solvate and/or prodrug thereof:

• wherein:
• R is selected from H, C1-2alkyl and C1-2fluoroalkyl;
• R1 is (CR5R5′)PO(OR6)2, wherein R5 is selected from PO(OR6′)2, CO2R6′, C(O)NHR7, SO3R7 and SO2NHR7;
• R5′ is selected from H, OH and halo;
• R6 and R6′ are independently selected from H and C1-6alkyl;
• and R7 is selected from H, OH and C1-6alkyl;
• X is selected from O, CH2, NH and N(C1-4alkyl);
• Z and Y are independently selected from S, O, NR3 and CR3R3′;
• Cy1 is selected from C6-10aryl, C5-10heteroaryl, C3-10cycloalkyl and C3-10heterocycloalkyl, each of which are unsubstituted or substituted with one or two substituents independently selected from halo, cyano, hydroxyl, NH2, NHC1-6alkyl, NHC3-6cycloalkyl, N(C1-6alkyl)(C1-6alkyl), C1-6fluoroalkyl, C1-6alkyl, C3-6cycloalkyl, C1-6fluoroalkoxy, C3-6cycloalkoxy and C1-6alkoxy;
• Cy2 is selected from C3-10cycloalkyl, C3-10heterocycloalkyl, C6-10aryl and C5-10heteroaryl, each of which is unsubstituted or substituted with one to three substituents independently selected from halo, cyano, hydroxyl, NH2, NHC1-6alkyl, NHC3-6cycloalkyl, N(C1-6alkyl)(C1-6alkyl), C1-6fluoroalkyl, C1-6alkyl, C3-6cycloalkyl, C1-6fluoroalkoxy, C3-6cycloalkoxy, phenyl, C3-6heterocycloalkyl, C5-6heteroaryl and C1-6alkoxy;
• L is selected from a direct bond, C(O), O, AC(O)(CR4R4′)m(A′)p, ASO2(CR4R4′)m(A′)p, C(O)A(CR4R4′)m(A′)p and SO2A(CR4R4′)m(A′)p;
• R3 and R3′ are independently selected from H, C3-6cycloalkyl and C1-4alkyl, or when the atom to which R3 is attached is sp2 hybridized, R3 is not present;
• R4 and R4′ are independently selected from H, halo, C1-4fluoroalkyl, C1-4alkyl, C3-6cycloalkyl, C1-4fluoroalkoxy, C3-6cycloalkoxy and C1-4alkoxy;
• m is selected from 0, 1 and 2;
• p is selected from 0 and 1;
• A is selected from NH and N(C1-4 alkyl);
• A′ is selected from O, NH and N(C1-4 alkyl) when m is 1 or 2 and A′ is selected from NH and N(C1-4 alkyl) when m is 0;
• and
• represents a single or double bond, provided that two double bonds are not adjacent to each other.