Rocaglate derivatives and uses thereof

A compound of Formula (I):

• wherein:
• Ring A is aryl or heteroaryl;
• Y is O, S, NRYA, CRYARYB, C═CRYARYB, SO or SO2,
• where RYA and RYB are independently aryl, heteroaryl, cycloalkyl, heterocyclyl, H, halogen, cyano (CN), alkyl, haloalkyl, alkenyl, alkynyl, ORA, NRARB, —C(O)RA, C(O)NHRA, C(O)NRARB, C(O)[alkylene]NHRA, C(O)[alkylene]NRARB, CO2RA, C(S)NHRA, C(S)NRARB, SRA, S(O)RA, SO2RA, SO2NHRA, SO2NRARB, NHC(O)RA, NRAC(O)RB, NHC(O)NHRA, NHC(O)NRARB, NRAC(O)NHRB, NRAC(O)NRBRC, P(O)(OH)(ORA), or P(O)(ORA)(ORB);
• R1 is aryl, heteroaryl, cycloalkyl, heterocyclyl, H, halogen, CN, alkyl, haloalkyl, alkenyl, alkynyl, ORA, NRARB, —C(O)RA, C(O)NHRA, C(O)NRARB, C(O)[alkylene]NHRA, C(O)[alkylene]NRARB, CO2RA, C(S)NHRA, C(S)NRARB, SRA, S(O)RA, SO2RA, SO2NHRA, SO2NRARB, NHC(O)RA, NRAC(O)RB, NHC(O)NHRA, NHC(O)NRARB, NRAC(O)NHRB, NRAC(O)NRBRC, P(O)(OH)(ORA), or P(O)(ORA)(ORB);
• R2 is aryl, heteroaryl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, H, halogen, CN, haloalkyl, ORA, NRARB, —C(O)RA, C(O)NHRA, C(O)NRARB, C(O)[alkylene]NHRA, C(O)[alkylene]NRARB, CO2RA, C(S)NHRA, C(S)NRARB, SRA, S(O)RA, SO2RA, SO2NHRA, SO2NRARB, NHC(O)RA, NRAC(O)RB, NHC(O)NHRA, NHC(O)NRARB, NRAC(O)NHRB, NRAC(O)NRBRC, P(O)(OH)(ORA), or P(O)(ORA)(ORB);
• RE is —SO2—R3 or CN;
• R3 is NRN1RN2, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, H, halogen, CN, haloalkyl, ORA, —C(O)RA, C(O)NHRA, C(O)NRARB, C(O)[alkylene]NHRA, C(O)[alkylene]NRARB, CO2RA, C(S)NHRA, C(S)NRARB, SRA, S(O)RA, SO2RA, SO2NHRA, SO2NRARB, NHC(O)RA, NRAC(O)RB, NHC(O)NHRA, NHC(O)NRARB, NRAC(O)NHRB, NRAC(O)NRBRC, P(O)(OH)(ORA), or P(O)(ORA)(ORB);
• wherein
• RN1 and RN2 are independently H, alkyl, alkenyl, cycloalkyl, heterocyclyl, H, halogen, CN, haloalkyl, ORA, —C(O)RA, C(O)NHRA, C(O)NRARB, C(O)[alkylene]NHRA, C(O)[alkylene]NRARB, CO2RA, C(S)NHRA, C(S)NRARB, SRA, S(O)RA, SO2RA, SO2NHRA, SO2NRARB, NHC(O)RA, NRAC(O)RB, NHC(O)NHRA, NHC(O)NRARB, NRAC(O)NHRB, NRAC(O)NRBRC, P(O)(OH)(ORA), or P(O)(ORA)(ORB);
• or RN1 and RN2 together with the nitrogen they are attached to form a heterocyclyl or heteroaryl;
• R4 is OR4A, H, halogen, CN, alkyl, haloalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, NRARB, —C(O)RA, C(O)NHRA, C(O)NRARB, C(O)[alkylene]NHRA, C(O)[alkylene]NRARB, CO2RA, C(S)NHRA, C(S)NRARB, SRA, S(O)RA, SO2RA, SO2NHRA, SO2NRARB, NHC(O)RA, NRAC(O)RB, NHC(O)NHRA, NHC(O)NRARB, NRAC(O)NHRB, NRAC(O)NRBRC, P(O)(OH)(ORA), or P(O)(ORA)(ORB);
• R5 is OR5A, H, halogen, CN, alkyl, haloalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, NRARB, —C(O)RA, C(O)NHRA, C(O)NRARB, C(O)[alkylene]NHRA, C(O)[alkylene]NRARB, CO2RA, C(S)NHRA, C(S)NRARB, SRA, S(O)RA, SO2RA, SO2NHRA, SO2NRARB, NHC(O)RA, NRAC(O)RB, NHC(O)NHRA, NHC(O)NRARB, NRAC(O)NHRB, NRAC(O)NRBRC, P(O)(OH)(ORA), or P(O)(ORA)(ORB);
• or
• R5 together with the carbon R4 is attached to forms a heterocyclyl;
• and RA, RB, R4A and R5A are independently H, substituted or unsubstituted (C1-C8) alkyl, (C1-C8) haloalkyl, (C1-C8) branched alkyl, (C1-C8) linear alkyl, (C1-C8) cycloalkyl, (C1-C8) aryl or phenyl, (C1-C8) alkenyl, or (C1-C8)alkynyl;
• or a solvate, stereoisomer, or pharmaceutical acceptable salt thereof, and
• wherein any alkyl, alkenyl, cycloalkyl, heterocyclyl, heteroaryl or aryl is optionally substituted with 1, 2, 3, 4 or more substituents selected independently from the group consisting of heterocycle, OH, oxo (═O), CN, SH, SO2NH2, SO2(C1-C4)alkyl, SO2NH(C1-C4)alkyl, halogen, NH2, NH(C1-C4)alkyl, N[(C1-C4)alkyl]2, C(O)NH2, COOH, COOMe, acetyl, (C1-C8)alkyl, O(C1-C8)alkyl, O(C1-C8)haloalkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, haloalkyl, thioalkyl, cyanomethylene, alkylaminyl, NH2—C(O)-alkylene, NH(Me)-C(O)-alkylene, CH2—C(O)-lower alkyl, C(O)-lower alkyl, alkylcarbonylaminyl, CH2—[CH(OH)]m—(CH2)p—OH, CH2—[CH(OH)]m—(CH2)p—NH2 and CH2-aryl-alkoxy, where “m” and “p” are independently 1, 2, 3, 4, 5 or 6.