Compositions and methods for immune modulation and treatment of cancer
AssigneeBoard of Trustees of Michigan State University
InventorsKaren Liby, Ana Sofia Mendes Leal, Edmund Ellsworth, Bilal Abou Aleiwi
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Abstract
The disclosure relates to rexinoids, including compounds of the Formula (I) and (II) or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof. These rexinoids are useful for increasing PD-L1 in vivo, for treatment of cancer, and for inhibiting the onset of cancer.
Claims46
A compound of the Formula (I):
- or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof, wherein:
- X1 is C═C(R6R7), CR6R7 or NR5, wherein R6-R8 are each independently H or alkyl or the R6 and R7 groups on CR6R7, together with the carbon atom to which they are attached, form a cycloalkyl or heterocyclyl group;
- each X2 is, independently, N or CR9, wherein R9 is H or R8 and R9, together with the atoms to which they are each attached, form a heterocyclyl group;
- X3 is CH or N;
- X4 is N or C;
- R1 is alkyl;
- R2 is H, alkyl or alkoxy, provided in some cases that when X2 is N and X3 is CPI, then R2 is not isobutoxy;
- R4 is absent, H alkyl or alkoxy;
- R3 is H or alkyl;
- and
- R5 is H or alkyl;
- or R2 and R3 or R3 and R4, together with the carbon atoms to which they are attached, form a cycloalkyl group;
- wherein the compound of Formula (I) is at least disubstituted with R1-R4.
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A method comprising administering a compound of the Formula (II to a subject:
- or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof, wherein:
- X1 is C═C(R6R7), CR6R7 car NR8, wherein R6-R8 are each independently H or alkyl or the R6 and R7 groups on CR6R7, together with the carbon atom to which they are attached, form a cycloalkyl, cycloalkenyl or heterocyclyl group;
- each X2 is, independently, N or CR9, wherein R9 is H or R8 and R9, together with the atoms to which they are each attached, form a heterocyclyl group;
- X3 is CH or N;
- X4 is N C;
- R10 and R11 form a ring, such as cycloalkyl, cycloalkenyl or a heterocyclyl ring;
- R4 is absent, H, alkyl or alkoxy;
- R3 is H or alkyl;
- R5 is H or alkyl;
- or R2 and R3 or R3 and R4, together with the carbon atoms to which they are attached, form a cycloalkyl group;
- and
- R12 and R13 are each, independently, H or halo, such as chloro, bromo or fluoro.
Dependencies are inferred from the claim text.