# US 9,040,527 B2 · Pyrimidinediamine kinase inhibitors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,040,527 B2 - Document ID: US9040527B2 - Status: Granted - Kind: B2 - Application number: 13/948,342 - Filed: 2013-07-23 - Published: 2013-11-21 - Granted: 2015-05-26 - Earliest claimed: 2008-12-30 - Assignees: Rigel Pharmaceuticals, Inc. - Applicants: Rigel Pharmaceuticals, Inc. - Inventors: Rajinder Singh; Andy Atuegbu; John Ramphal; Hui Li; Marina Gelman; Jeffrey Clough; Carlos Valdez; Somasekhar Bhamidipati; Sambaiah Thota; Darren McMurtrie - Web page: https://patentgrep.com/patent/US9040527B2 ## CPC - A61K 31/5383: ortho- or peri-condensed with heterocyclic ring systems - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07D 413/12: linked by a chain containing hetero atoms as chain links - C07D 413/14: containing three or more hetero rings - C07D 417/12: linked by a chain containing hetero atoms as chain links - C07D 487/08: Bridged systems - C07D 498/04: Ortho-condensed 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 Disclosed embodiments provide pyrimidinediamine compounds useful for inhibiting kinase activity, including the activity of polo-like kinase 1 (PLK1). Also disclosed are pharmaceutical compositions comprising these compounds and methods of treating diseases associated with kinase activity, in particular enhanced PLK1 catalytic activity, such as diseases associated with abnormal cell proliferation, including neoplastic disorders. ## Claims ### Claim 1 6-(2-(2-ethoxy-5-(4-methylpiperazin-1-yl)phenylamino)-5-fluoropyrimidin-4-ylamino)-2H-pyrido[3,2-b][1,4]oxazine-3(4H)-one, or a solvate, pharmaceutically acceptable salt, or N-oxide thereof. ### Claim 2 A method of treating a disease or condition, comprising administering to a mammal a therapeutically effective amount of 6-(2-(2-ethoxy-5-(4-methylpiperazin-1-yl)phenylamino)-5-fluoropyrimidin-4-ylamino)-2H-pyrido[3,2-b][1,4]oxazine-3(4H)-one, or a solvate, pharmaceutically acceptable salt, or N-oxide thereof, wherein the disease or condition is ductal carcinoma, invasive lobular carcinoma, lobular carcinoma in situ, metastatic breast cancer, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Kaposi's sarcoma, small cell lung carcinoma, non-small cell lung carcinoma, bronchial adenoma, pleuropulmonary blastoma, malignant mesothelioma, brain stem glioma, hyptothalamic glioma, cerebellar astrocytoma, cerebral astrocytoma, medullablastoma, ependymal tumors, oligodendroglial, meningiomas, neuroectodermal tumor, pineal tumor, prostate cancer, testicular cancer, penile cancer, uterine cancer (endometrial), cervical cancer, ovarian cancer, vaginal cancer, vulval cancer, uterine sarcoma, ovarian germ cell tumor, anal cancer, colon cancer, colorectal cancer, esophageal cancer, gallbladder cancer, stomach (gastric) cancer, pancreatic cancer, pancreatic cancer-Islet cell, rectal cancer, small-intestine cancer, salivary gland cancer, hepatocellular carcinoma, cholangiocarcinoma, mixed hepatocellular cholangiocarcinoma, primary liver cancer, intraocular melanoma, retinoblastoma, rhabdomyosarcoma, laryngeal cancer, hypopharyngeal cancer, nasopharyngeal cancer, oropharyngeal cancers, lip cancer, oral cancer, squamous neck cancer, metastatic paranasal sinus cancer, T cell lymphoma, B cell lymphoma, non-Hodgkin's lymphoma, cutaneous T cell lymphoma, Hodgkin's disease, lymphoma of the central nervous system, acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, hair cell leukemia, thyroid cancer, thymoma, malignant thymoma, bladder cancer, soft tissue sarcoma, osteosarcoma, malignant fibrous histiocytoma, lymphosarcoma, or rhabdomyosarcoma. ### Claim 3 A pharmaceutical composition, comprising 6-(2-(2-ethoxy-5-(4-methylpiperazin-1-yl)phenylamino)-5-fluoropyrimidin-4-ylamino)-2H-pyrido [3,2-b][1,4]oxazine-3(4H)-one, or a solvate, pharmaceutically acceptable salt, or N-oxide thereof. ### Claim 4 (depends on 3) The composition according to claim 3 formulated for topical administration, ocular administration, oral administration, buccal administration, systemic administration, nasal administration, injection administration, transdermal administration, rectal administration, or vaginal administration. ### Claim 5 (depends on 3) The composition according to claim 3 formulated for inhalation or insufflation. ### Claim 6 (depends on 3) The composition according to claim 3 further comprising a suspending agent, a stabilizing agent, a dispersing agent, a buffer, a dextrose solution, a penetrant, a binding agent, a filler, a lubricant, a disintegrant, a wetting agent, a coating agent, a suspending agent, an emulsifying agent, a preservative, a flavoring agent, a coloring agent, a sweetening agent, or combinations thereof. ### Claim 7 A method for inhibiting an activity of a kinase, comprising contacting the kinase with an effective amount of 6-(2-(2-ethoxy-5-(4-methylpiperazin-1-yl)phenylamino)-5-fluoropyrimidin-4-ylamino)-2H-pyrido[3,2-b][1,4]oxazine-3 (4H)-one, or a solvate, pharmaceutically acceptable salt or N-oxide thereof. ### Claim 8 (depends on 7) The method according to claim 7 wherein the kinase is a PLK. ### Claim 9 (depends on 7) The method according to claim 7 wherein the kinase is selected from PLK1, PLK2, PLK3 or PLK4. ### Claim 10 (depends on 7) The method according to claim 7 wherein the kinase is PLK1. ### Claim 11 (depends on 7) The method according to claim 7 comprising contacting the kinase in vivo.