CD73 inhibitors
AssigneeEli Lilly and Company
InventorsRobert Dean Dally, Maria Cristina Garcia Paredes, Lawrence Joseph Heinz, II, Jennifer Marie Howell, Frank George Njoroge, Yan Wang, Genshi Zhao
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Abstract
The present invention provides 5-[5]-[2-cycloalkyl]-6-pyridazin-3-yl]-1H-pyrimidine-2,4-dione compounds, or pharmaceutically acceptable salts thereof, that inhibit the activity of CD73 and are useful in treating cancer.
Claims22
A compound of the formula:
- wherein n is 0-3;
- R1 is —H, —F, -gem-difluoro, -gem-dimethyl,
- —C1-4 alkyl, —CHF2, —CF2CH3 or —CH2CH2F;
- and
- R2 is selected from —H, —CH3, —F, —Cl, —CN, or —OCH3;
- or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition comprising a compound of the formula:
- wherein n is 0-3;
- R1 is —H, —F, -gem-difluoro, -gem-dimethyl, —C1-4 alkyl, —CHF2, —CF2CH3 or —CH2CH2F;
- and
- R2 is selected from —H, —CH3, —F, —Cl, —CN, or —OCH3;
- or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents, or excipients.
A method of treating cancer, comprising administering to a patient in need thereof, an effective amount of a compound of the formula:
- wherein n is 0-3;
- R1 is —H, —F, -gem-difluoro, -gem-dimethyl, —C1-4 alkyl, —CHF2, —CF2CH3 or —CH2CH2F;
- and
- R2 is selected from —H, —CH3, —F, —Cl, —CN, or —OCH3;
- or a pharmaceutically acceptable salt thereof,
- wherein the cancer is bladder cancer, breast cancer, cholangiocarcinoma, colorectal cancer, colon cancer, gastric cancer, gallbladder cancer, glioblastoma, head and neck cancer, liver cancer, lung cancer, lymphoma, medulloblastoma, melanoma, ovarian cancer, pancreatic cancer, prostate cancer or renal cancer.
A method, comprising determining CD73 activity in the serum of a patient to whom a compound of the formula:
- wherein n is 0-3;
- R1 is —H, —F, -gem-difluoro, -gem-dimethyl, —C1-4 alkyl, —CHF2, —CF2CH3 or —CH2CH2F;
- and
- R2 is selected from —H, —CH3, —F, —Cl, —CN, or —OCH3;
- or a pharmaceutically acceptable salt thereof, has been administered.
A method, comprising determining CD73 expression in tissue from a patient to whom a compound of the formula:
- wherein n is 0-3;
- R1 is —H, —F, -gem-difluoro, -gem-dimethyl, —C1-4 alkyl, —CHF2, —CF2CH3 or —CH2CH2F;
- and
- R2 is selected from —H, —CH3, —F, —Cl, —CN, or —OCH3;
- or a pharmaceutically acceptable salt thereof, has been administered.
Dependencies are inferred from the claim text.