Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions
AssigneeUniversity of Utah Research Foundation
InventorsHaitao Ji, Binxun Yu, Min Zhang, Wenxing Guo
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Abstract
In one aspect, the invention relates to substituted 1H-benzo[d][1,2,3]triazol-1-ol analgoues, derivatives thereof, and related compound; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders, e.g. various tumors and cancers, associated with β-catenin/Tcf protein-protein interaction dysfunction using the compounds and compositions. 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.
Claims18
A compound having a structure represented by a formula:
- wherein A1 is selected from —N═, —NH—, and —CR2a═;
- wherein A2 is selected from ═N—, (C═O), (C═S), and ═CR2b—;
- wherein A3 is selected from —N(OH)— and —O—;
- provided that valency is satisfied for A1, A2, and A3;
- wherein L is selected from —CH2—, —(CH2)2—, —(CH2)3—, —OCH2—, —NHCH2—, —CH2NHCH2—, and —CH2OCH2—;
- wherein B1 is selected from —N═, —O—, and —S—;
- wherein B2 is selected from ═N—, (C═O), (C═S), and (S═O);
- provided that valency is satisfied for B1 and B2;
- wherein each of R1a, R1b, and R1c is independently selected from hydrogen, halogen, —OH, —NH2, C1-C3 haloalkyl, C1-C3 polyhaloalkyl, and C1-C3 alkoxy;
- and
- wherein each of R2a and R2b is independently selected from hydrogen, halogen, —OH, —NH2, C1-C3 haloalkyl, C1-C3 polyhaloalkyl, and C1-C3 alkoxy;
- or pharmaceutically acceptable salt, ester, hydrate, solvate, or polymorph thereof.
A method for the treatment of a disorder of uncontrolled cellular proliferation associated with β-catenin/Tcf protein-protein interaction dysfunction in a mammal comprising the step of administering to the mammal an effective amount of at least one compound having a structure represented by a formula:
- wherein A1 is selected from —N═, —NH—, and —CR2a═;
- wherein A2 is selected from ═N—, (C═O), (C═S), and ═CR2b—;
- wherein A3 is selected from —N(OH)— and —O—;
- provided that valency is satisfied for A1, A2, and A3;
- wherein L is selected from —CH2—, —(CH2)2—, —(CH2)3—, —OCH2—, —NHCH2—, —CH2NHCH2—, and —CH2OCH2—;
- wherein B1 is selected from —N═, —O—, and —S—;
- wherein B2 is selected from ═N—, (C═O), and (C═S);
- provided that valency is satisfied for B1 and B2;
- wherein each of R1a, R1b, and R1c is independently selected from hydrogen, halogen, —OH, —NH2, C1-C3 haloalkyl, C1-C3 polyhaloalkyl, and C1-C3 alkoxy;
- and
- wherein each of R2a and R2b is independently selected from hydrogen, halogen, —OH, —NH2, C1-C3 haloalkyl, C1-C3 polyhaloalkyl, and C1-C3 alkoxy;
- or pharmaceutically acceptable salt, ester, hydrate, solvate, or polymorph thereof.
Dependencies are inferred from the claim text.