Mutant KRas inhibitors
Compositions and methods for inhibits the binding of GTP to oncogenic mutant KRas are disclosed. These compositions may be used in method to treat a subject with cancer. In particular, the compositions may be used to treat cancers involving overactive Ras signaling.
1. A compound having Formula I:
wherein
R 1 is an alkyl group;
R 2 is a phenyl group optionally substituted with amino, alkyl, alkenyl, alkynyl, alkoxyl, aryl, carboxylate, cyano, guanidinyl, halogen, haloalkyl, heteroaryl having 2-8 carbon atoms and 1-3 heteroatoms selected from O, N and S, hydroxyl, nitrile, nitro, sulfinyl, sulfanyl, or mercapto; and
R 3 is H or an alkyl group;
or a pharmaceutical acceptable salt thereof.
2. The compound of claim 1 , wherein R 3 is alkyl.
3. The compound of claim 1 , wherein R 2 is unsubstituted phenyl.
4. The compound of claim 1 , wherein the compound has Formula IA
5. The compound of claim 1 , wherein the compound has Formula IB
wherein R 5 is hydrogen, amino, alkyl, alkenyl, alkynyl, alkoxyl, aryl, carboxylate, cyano, guanidinyl, halogen, haloalkyl, heteroaryl having 2-8 carbon atoms and 1-3 heteroatoms selected from O, N and S, hydroxyl, nitrile, nitro, sulfinyl, sulfanyl, or mercapto.
6. The compound of claim 1 , wherein R 1 is C 1-4 alkyl.
7. The compound of claim 1 , wherein the compound is
8. The compound of claim 1 , wherein the compound is
9. A pharmaceutical composition, comprising a therapeutically effective amount of a compound of claim 1 in a pharmaceutically acceptable excipient.