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US 2023/0146127 A1Published application
3-diarylmethylenes and uses thereof
AssigneeAtux Iskay LLC
InventorMichael Ohlmeyer
Life of this patent
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Abstract
3-Diarylmethylenes are disclosed. The compounds activate PP2A, suppress oncogenic kinase signaling, and negatively regulate MYC and MYCN in cancer. The compounds also induce FOXO transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a monotherapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.
Claims20
A compound having the following formula:
- or a pharmaceutically acceptable salt thereof,
- wherein
- is a single or a double bond;
- R1, R2, R5, and R6 are each, independently, H, halogen, NO2, C1-3 alkyl, C1-3 haloalkyl, O—(C1-3 alkyl), or O—(C1-3 haloalkyl);
- R3 and R4 are each, independently, H, halogen, NO2, C1-3 alkyl, C1-3 haloalkyl, O—(C1-3 alkyl), or O—(C1-3 haloalkyl), or R3 and R4 are covalently linked together to form C1-3 alkylene;
- R7 and R8, are each, independently, H, halogen, NO2, C1-3 alkyl, C1-3 haloalkyl, O—(C1-3 alkyl), O—(C1-3 haloalkyl), or N(H)C(O)O(C1-6 alkyl), or R7 and R8 are covalently linked together to form O(C1-3 alkylene)O or O(C1-3 haloalkylene)O;
- R9 and R10, are each, independently, H, OH, halogen, C1-3 alkyl, C1-3 haloalkyl, O—(C1-3 alkyl), O—(C1-3 haloalkyl), C1-3 alkylene-OH, or C1-3 alkylene-O—C1-3 alkyl;
- J1 is CH2, NH, S, or O;
- J2 is a bond or C1-3 alkylene;
- J3 is a bond or C1-3 alkylene;
- and
- J4 is C6-12 aryl or C2-9 heteroaryl, each heteroatom independently selected from N, O, or S.
9 more elements
A compound of formula I:
- wherein:
- B is absent or is selected from a direct bond, O, S, —CH2CH2— or —CH═CH—;
- Q is selected from —(CH2)n— with n=0, 1 or 2, —O—, —S—, or —SO2— NR5;
- U is a group selected from:
- X1, X2, X3, and X4 are independently selected in each instance from hydrogen, halogen, nitro, cyano, (C1-C6)alkyl optionally substituted with —OH, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, (C1-C6)haloalkylthio, —NR1R2, —OR1, —C(O)R1, —OC(O)R1, —C(O)NR1R2, —C(O)OR1, —SR1, —SO2R1, and —SO2NR1R2;
- R1 and R2 are independently selected in each instance from hydrogen and (C1-C6)alkyl;
- Z1 and Z2 are independently selected in each instance from hydrogen, halogen, nitro, cyano, azido, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, (C1-C6)haloalkylthio, —NR3R4, —NR3C(O)R4, —NR3C(O)OR5, —OR3, —C(O)R3, —OC(O)R3, —C(O)NR3R4, —C(O)OR3, —SR3, —SO2R3, and —SO2NR3R4;
- R3, R4 and R3 are independently selected from lower alkyl groups and R3 and R4 may be joined to form a ring.
- R5 is selected from optionally substituted lower alkyl, lower cycloalkyl, acyl.
6 more elements
A compound having the following formula:
- or a pharmaceutically acceptable salt thereof, is a single or a double bond;
- J5 is
- J6 is
- J7 is
1 more element
Dependencies are inferred from the claim text.