# US 10,500,213 B2 · Compounds that inhibit Mcl-1 protein > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,500,213 B2 - Document ID: US10500213B2 - Status: Granted - Kind: B2 - Application number: 16/297,904 - Filed: 2019-03-11 - Published: 2019-07-04 - Granted: 2019-12-10 - Earliest claimed: 2017-03-30 - Assignees: Amgen Inc. - Applicants: Amgen Inc. - Inventors: Sean P. Brown; Kexue Li; Yunxiao Li; Markian M. Stec - Web page: https://patentgrep.com/patent/US10500213B2 ## CPC - A61K 31/553: having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - C07D 498/08: Bridged systems - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, or a stereoisomer thereof; and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer. ## Claims ### Claim 1 A method of treating cancer, the method comprising: administering to a patient in need thereof, a therapeutically effective amount of a compound, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the stereoisomer thereof, wherein the cancer is a hematologic malignancy and further wherein the compound is selected from: ### Claim 2 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt thereof is administered to the patient. ### Claim 3 A method of treating cancer, the method comprising: administering to a patient in need thereof, a therapeutically effective amount of a compound, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the stereoisomer thereof, wherein the cancer is selected from the group consisting of breast cancer, colorectal cancer, skin cancer, melanoma, ovarian cancer, kidney cancer, lung cancer, non-small cell lung cancer, lymphoma, non-Hodgkin's lymphoma, myeloma, multiple myeloma, leukemia, and acute myelogenous leukemia, and further wherein the compound is selected from: ### Claim 4 (depends on 1) The method of claim 1, wherein the cancer is multiple myeloma. ### Claim 5 (depends on 1) The method of claim 1, wherein the cancer is acute myelogenous leukemia. ### Claim 6 (depends on 1) The method of claim 1, wherein the cancer is non-Hodgkin's lymphoma. ### Claim 7 (depends on 1) The method of claim 1, further comprising administering to the patient in need thereof a therapeutically effective amount of an additional pharmaceutically active compound. ### Claim 8 (depends on 7) The method of claim 7, wherein the additional pharmaceutically active compound is carfilzomib. ### Claim 9 (depends on 7) The method of claim 7, wherein the additional pharmaceutically active compound is venetoclax. ### Claim 10 (depends on 7) The method of claim 7, wherein the additional pharmaceutically active compound is cytarabine. ### Claim 11 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 12 (depends on 11) The method of claim 11, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 13 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 14 (depends on 13) The method of claim 13, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 15 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 16 (depends on 15) The method of claim 15, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 17 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 18 (depends on 17) The method of claim 17, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 19 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 20 (depends on 19) The method of claim 19, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 21 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 22 (depends on 21) The method of claim 21, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 23 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 24 (depends on 23) The method of claim 23, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 25 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 26 (depends on 25) The method of claim 25, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 27 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 28 (depends on 27) The method of claim 27, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 29 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 30 (depends on 29) The method of claim 29, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 31 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 32 (depends on 31) The method of claim 31, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 33 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 34 (depends on 33) The method of claim 33, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 35 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 36 (depends on 35) The method of claim 35, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 37 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 38 (depends on 37) The method of claim 37, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 39 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 40 (depends on 39) The method of claim 39, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 41 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 42 (depends on 41) The method of claim 41, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 43 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 44 (depends on 43) The method of claim 43, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma. ### Claim 45 (depends on 1) The method of claim 1, wherein the compound or the pharmaceutically acceptable salt is administered to the patient, and the compound is ### Claim 46 (depends on 45) The method of claim 45, wherein the cancer is selected from multiple myeloma, acute myelogenous leukemia, or non-Hodgkin's lymphoma.