Inhibitors of dyrk and pim

A compound, comprising Formula I:

• or a pharmaceutically acceptable salt thereof, wherein
• W is an optionally substituted C,
• at least one of X1, X2, X3, X4 is independently selected from OH, O—CH3, and a halogen,
• Y1, Y2, Y3, Y4 and Y5 are each independently selected from H, CH3, OH, O—CH3, NO2, and an electrophile, at least one of Y1, Y2, Y3, Y4, and Y5 is independently selected from OH and O—CH3, and a halogen, and optionally Y2 and Y3 form a five-membered ring including one or more heteroatom, wherein the one or more heteroatom is selected from O, N, and S, and the five-membered ring is optionally substituted with a ═C, ═S, or an electrophile, and
• no more than five of X1, X2, X3, X4, Y1, Y2, Y3, Y4, and Y5 is H, and no more than one of X1, X2, X3, X4, Y1, Y2, Y3, Y4, and Y5, is O—CH3.

A compound, comprising Formula Ia:

• or a pharmaceutically acceptable salt thereof, wherein
• X1, X2, X3, and X4 are each independently H, OH, or an electrophile, and optionally one pair selected from X1 and X2, X2 and X3, and X3 and X4 forms a five-membered ring including one or more heteroatom, wherein the one or more heteroatom is selected from O, N, and S, and the five-membered ring is optionally substituted with a ═C, an ═S, or an electrophile, and
• Y1, Y2, Y3, Y4 and Y5 are each independently selected from H, CH3, OH, O—CH3, NO2, and an electrophile, and optionally Y2 and Y3 form a five-membered ring including one or more heteroatom, wherein the one or more heteroatom is selected from O, N, and S, and the five-membered ring is optionally substituted with a ═C, ═S, or an electrophile,
• with the caveats that
• (a) if the pair X2 and X3 together form a dioxolane then optionally Y2 and Y3 form a pyrroline optionally substituted with a ═C, ═S, or an electrophile, and no more than one of Y1, Y2, Y3, Y4 and Y5 is OH,
• (b) if one or more of Y1, Y2, Y3, Y4 and Y5 is O—CH3, then X2 and X3 form a five-membered ring including one or more heteroatom, wherein the one or more heteroatom is selected from N and S, and the five-membered ring is optionally substituted with a ═C, ═S, or an electrophile, and
• (c) if X3 is OH and one or both of Y3 and Y4 are OH then Y5 is OH.

A compound, comprising Formula Ia:

• or a pharmaceutically acceptable salt thereof, wherein
• X1, X2, X3, and X4 are each independently H, OH, or an electrophile, and optionally one pair selected from X1 and X2, X2 and X3, and X3 and X4 forms a five-membered ring including one or more heteroatom, wherein the one or more heteroatom is selected from O, N, and S, and the five-membered ring is not a dioxolane and is optionally substituted with a ═C, an ═S, or an electrophile, and
• Y1, Y2, Y3, Y4 and Y5 are each independently selected from H, CH3, OH, O—CH3, NO2, and an electrophile, and optionally Y2 and Y3 form a five-membered ring including one or more heteroatom, wherein the one or more heteroatom is selected from O, N, and S, and the five-membered ring is optionally substituted with a ═C, ═S, or an electrophile,
• with the caveats that
• (a) if one or more of Y1, Y2, Y3, Y4 and Y5 is O—CH3, then X2 and X3 form a five-membered ring including one or more heteroatom, wherein the one or more heteroatom is selected from N and S, and the five-membered ring is optionally substituted with a ═C, ═S, or an electrophile, and
• (b) if X3 is OH and one or both of Y3 and Y4 are OH then Y5 is OH.

A compound, comprising Formula Ia:

• or a pharmaceutically acceptable salt thereof, wherein
• X1, X2, X3, and X4 are each independently H, OH, or an electrophile, and optionally one pair selected from X1 and X2, X2 and X3, and X3 and X4 forms a five-membered ring including one or more heteroatom, wherein the one or more heteroatom is selected from O, N, and S, and the five-membered ring is optionally substituted with a ═C, an ═S, or an electrophile, and
• Y1, Y2, Y3, Y4 and Y5 are each independently selected from H, CH3, OH, NO2, and an electrophile, and optionally Y2 and Y3 form a five-membered ring including one or more heteroatom, wherein the one or more heteroatom is selected from O, N, and S, and the five-membered ring is optionally substituted with a ═C, ═S, or an electrophile,
• with the caveats that
• (a) if the pair X2 and X3 together form a dioxolane then optionally Y2 and Y3 form a five-membered ring including one or more heteroatom only if Y2 and Y3 form a pyrroline optionally substituted with a ═C, ═S, or an electrophile, and no more than one of Y1, Y2, Y3, Y4 and Y5 is OH, and.
• (b) if X3 is OH and one or both of Y3 and Y4 are OH then Y5 is OH