Purine diones as Wnt pathway modulators

Patent metadata

Field	Value
Publication number	US-10844063-B2
Application number	US-201916716268-A
Country	US
Kind code	B2
Filing date	Dec 16, 2019
Priority date	May 23, 2013
Publication date	Nov 24, 2020
Grant date	Nov 24, 2020

Abstract

The invention relates to the use of compounds of general structure (I) in modulation of the Wnt pathway [Formula should be inserted here] wherein R 1 , R 2 , R 3 , R 4 and R 5 are each, independently, H or an alkyl group; D is selected from the group consisting of H, halogen, alkyl, cycloalkyl, aryl, and dialkylamino, each (other than H and halogen) being optionally substituted; Ar is an aryl or heteroaryl group, optionally substituted; Cy is an aryl, heteroaryl or a saturated ring containing at least one heteroatom, each being optionally substituted; and n is an integer from 1 to 3.

First claim

The invention claimed is:

1. A method of inhibiting Wnt signaling pathway, comprising contacting a cell with of a compound of Formula (I):

wherein:
R 1 , R 2 , R 3 , R 4 and R 5 are each, independently, H or an alkyl group;
D is selected from the group consisting of H, halogen, alkyl, cycloalkyl, aryl, and dialkylamino, each (other than H and halogen) being optionally substituted;
Ar is a 6-membered heteroaryl ring having 1 or 2 nitrogen atoms having no substituents other than Cy and the amide nitrogen atom depicted in structure (I), these being in a 1,4-relationship on the ring; and
Cy is an aryl, heteroaryl or a saturated ring containing at least one heteroatom, each being optionally substituted; and
n is an integer from 1 to 2;
or an enantiomer, diastereomer or salt thereof.

2. The method of claim 1 , comprising contacting a Wnt protein associated with the cell with the compound of Formula (I).

3. The method of claim 2 , wherein the Wnt protein is a Wnt-3A protein.

4. The method of claim 1 , wherein the compound of Formula (I) inhibits the Wnt signaling pathway.

5. The method of claim 1 , wherein the cell is of a disease or condition selected from cancer, fibrosis, a degenerative disease, a diabetic retinopathy, a stem cell retinopathy, rheumatoid arthritis, psoriasis or myocardial infarction.

6. The method of claim 5 , wherein the cancer is selected from the group consisting of cervical, colon, breast, bladder, head and neck, gastric, lung, ovarian, prostate, thyroid, non-small-cell lung, chronic lymphocytic leukemia, mesothelioma, melanoma, pancreatic adenocarcinoma, basal cell carcinoma, osteosarcoma, hepatocellular carcinoma, Wilm's tumor or medulloblastoma.

7. The method of claim 5 , wherein the fibrosis is selected from the group consisting of pulmonary fibrosis, liver fibrosis, skin fibrosis or renal fibrosis.

Assignees

• Agency Science Tech & Res

Inventors

• Ho Soo Yei
• Blanchard Stephanie Eliane
• Duraiswamy Athisayamani Jeyaraj
• Alam Jenefer
• Adsool Vikrant Arun

Classifications

• C07D473/08

  with methyl radicals in positions 1 and 3, e.g. theophylline · CPC title

• C07D473/06 Primary

  with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K31/522

  having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir · CPC title