Small Molecule Compounds and Compositions
OwnerKatherine Widdowson, Robert Joseph Allen Bell +6inventors
InventorsKatherine Widdowson, Robert Joseph Allen Bell, Santosh Kulkarni, Adrian Hall, Mark Patrick Healy, David George Hubert Livermore, James William Myatt, Mairi Simie
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Abstract
Provided herein are compounds and compositions that inhibit telomerase and/or the TERT gene with a mutant promoter. Further provided are small molecule compounds or compositions having beneficial effects in cancer treatment. Methods of making the compounds and compositions and methods of using the compounds and compositions, such as using the compounds and compositions to treat cancer, are also provided.
Claims48
A compound having a structure of Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein
- Ra each individual Rb and each individual Rb′ are independently H, halogen, or optionally substituted C1-C4 alkyl (e.g., methyl);
- wherein optionally Ra and Rb are joined to form a 5 or 6 membered ring;
- Rc is carboxylic acid or its isostere;
- Rd is an optionally substituted aryl or heteroaryl group;
- and
- Re is an optionally substituted aryl or heteroaryl group.
A compound having a structure of Formula (II):
- or a pharmaceutically acceptable salt thereof, wherein
- R1 each individual R2 and each individual R2′ are independently H, halogen, or optionally substituted C1-C4 alkyl;
- wherein optionally R1 and R2 are joined to form a 5 or 6 membered ring;
- R3, R3′, R4, R4′ or R5 is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxyl, optionally substituted amine, optionally substituted amide, optionally substituted sulfone, optionally substituted heteroaryl, azide (N3), nitrile (CN), or CF3;
- wherein optionally R4 and R5 together with the carbon atoms they are attached to form an optionally substituted aromatic ring, wherein at least 3 of R3, R3′, R4, R4′ and R5 are H;
- and
- R6, R6′, R7, R7′ or R8 is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxyl, optionally substituted amine, optionally substituted amide, optionally substituted sulfone, optionally substituted heteroaryl, azide (N3), nitrile (CN), or CF3, wherein at least 3 of R6, R6′, R7, R7′ and R8 are H.
A compound having a structure of Formula (III):
- or a pharmaceutically acceptable salt thereof, wherein
- R1 and R2 are independently H or optionally substituted C1-C4 alkyl;
- wherein optionally R1 and R2 are joined to form a 5 or 6 membered ring;
- R3, R3′, R4, R4′ or R5 is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxyl, optionally substituted amine, optionally substituted amide, optionally substituted sulfone, optionally substituted heteroaryl, azide (N), nitrile (CN), or CF3, wherein at least 3 of R3, R3′, R4, R4′ and R5 are H;
- and
- R6, R6′, R7, R7′ or R8 is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxyl, optionally substituted amine, optionally substituted amide, optionally substituted sulfone, optionally substituted heteroaryl, azide (N3), nitrile (CN), or CF3, wherein at least 3 of R6, R6′, R7, R7′ and R8 are H.
A compound selected from the group consisting of Compound 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, and 149, or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.