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US 11,505,531 B2Granted
Piperazine-2,5-diones as TGF-beta inhibitors
AssigneesThe UAB Research Foundation, Southern Research Institute
InventorsMark J. Suto, Vandana V. Gupta, Wei Zhang, Joanne Murphy-Ullrich
Life of this patent
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Abstract
The present disclosure is concerned with piperazine-2,5-diones that are capable of inhibiting TGF-β and methods of treating cancers such as, for example, multiple myeloma and a hematologic malignancy, and methods of treating fibrotic conditions using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Claims12
A compound having a structure represented by a formula:
- wherein n is selected from 1, 2, 3, and 4;
- wherein each of R1a and R1b is independently C1-C4 alkyl;
- or wherein each of R1a and R1b are optionally covalently bonded together and, together with the intermediate atoms, comprise a 3- to 7-membered cycloalkyl substituted with 0-4 non-hydrogen groups independently selected from halogen, —NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino;
- and
- wherein each of R2 and R3 is independently selected from hydrogen and C1-C4 alkyl;
- and
- wherein R4 is selected from —NR20aR20b and Cy1;
- wherein each of R20a and R20b, when present, is independently selected from hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, cycloalkyl, and heteroaryl;
- wherein Cy1, when present, is selected from C5-C6 cycloalkyl, monocyclic heteroaryl, and —C6H4R21 and is substituted with 0-4 non-hydrogen groups independently selected from halogen, —NH2, C1-C4 alkyl, C1-C4 haloalkylh, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino;
- and
- wherein R21, when present, is selected from —(CH2)qNR31aR31b and —C(O)NR32aR32b;
- wherein q, when present, is selected from 0 and 1;
- wherein each of R31a, R31b, R32a, and R32b, when present, is independently selected from hydrogen and C1-C4 alkyl;
- or wherein each of R1a and R1b is hydrogen and R4 is —C6H4C(O)NR32aR32b;
- or wherein R1a is hydrogen, R1b is —CH2Cy2, and R4 is —C6H4R21;
- wherein Cy2 is selected from C3-C6 cycloalkyl substituted with 0-4 non-hydrogen groups independently selected from halogen, —NH2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino;
- provided that when n is 1 and each of R1a and R1b together comprise a 3-membered cycloalkyl then Cy1, when present, is not monocyclic heteroaryl, and
- provided that when R4 is NR20aR20b then each of R1a and R1b is independently C1-C4 alkyl,
- or a pharmaceutically acceptable salt thereof.
16 more elements
Dependencies are inferred from the claim text.