A tricyclic derivative useful as a PARP7 inhibitor.

Abstract

Provided are compounds of formula (I), their stereoisomers, their deuterated derivatives, or pharma- ceutically acceptable salts, intermediates for preparing the compounds, processes for preparing the compounds, compositions comprising same, and methods of using same, that inhibit the activity of PARP7. [Formula 1] TIFF2024506612000898.tif34170

Claims

1. A compound, its stereoisomer, its deuterated derivative, or a pharmaceutically acceptable salt thereof; a compound, its stereoisomer, its deuterated derivative, or a pharmaceutically acceptable salt thereof, selected from any one of the following compounds: 【Chemistry 1】 【change】

2. A pharmaceutical composition comprising the compound described in claim 1, a stereoisomer thereof, a deuterated derivative thereof, or a pharmaceutically acceptable salt thereof; and at least one pharmaceutically acceptable excipient.

3. The pharmaceutical composition according to claim 2, for use in the treatment of cancer related to PARP7.

4. The pharmaceutical composition according to claim 3, wherein the cancer is a cancer associated with PARP7 overexpression.

5. The pharmaceutical composition according to claim 3, wherein the cancer is selected from breast cancer, central nervous system cancer, endometrial cancer, kidney cancer, colorectal cancer, lung cancer, esophageal cancer, tongue cancer, ovarian cancer, pancreatic cancer, prostate cancer, gastric cancer, mesothelioma, melanoma, fibrosarcoma, bladder cancer, rectal cancer, lymphoma, cervical cancer, head and neck cancer, upper respiratory tract and gastrointestinal cancer, colorectal cancer, urinary tract cancer, and colon cancer.

6. The pharmaceutical composition according to claim 3, wherein the cancer is independently selected from adenocarcinoma, squamous cell carcinoma, mixed adenosquamous cell carcinoma, and undifferentiated carcinoma.

7. The ovarian cancer is selected from high-grade serous ovarian adenocarcinoma, ovarian mucinous cystadenocarcinoma, and malignant ovarian Brenner tumor; The aforementioned kidney cancer is clear cell renal cell carcinoma; The aforementioned tongue cancer is squamous cell carcinoma of the tongue; The lung cancer is selected from lung adenocarcinoma, lung adenosquamous carcinoma, squamous cell lung cancer, large cell lung cancer, small cell lung cancer, papillary lung adenocarcinoma, and non-small cell lung cancer; The aforementioned pancreatic cancer is selected from pancreatic adenocarcinoma and pancreatic ductal adenocarcinoma; The esophageal cancer in question is squamous cell carcinoma of the esophagus; The aforementioned mesothelioma is a biphasic type of mesothelioma; The aforementioned central nervous system cancers are selected from glioma, glioblastoma, and glioblastoma multiforme; The aforementioned gastric cancer is gastric adenocarcinoma; The aforementioned breast cancer is selected from ductal carcinoma, glandular carcinoma, and HR+ breast cancer; The aforementioned bladder cancer is squamous cell carcinoma of the bladder; The aforementioned melanoma is a malignant melanoma; The aforementioned colon cancer is colon adenocarcinoma; The aforementioned head and neck cancer is head and neck small cell squamous cell carcinoma. The pharmaceutical composition according to claim 5.

Images