218772-92-0Relevant articles and documents
Polycyclic amide derivative as CDK9 inhibitor, and preparation method and application thereof
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, (2021/07/24)
The invention belongs to the technical field of polycyclic amide derivatives, and particularly relates to a polycyclic amide derivative as a CDK9 inhibitor, and a preparation method and application thereof. The polycyclic amide derivative shows excellent CDK9 enzyme inhibitory activity, and can be used for preparing drugs for treating cancers, especially hematologic cancers including acute myeloid leukemia, multiple myeloma, chronic lymphocytic leukemia, follicular lymphoma and the like and solid tumors, such as acute myeloid leukemia, multiple myeloma, chronic lymphocytic leukemia and follicular lymphoma, including breast cancer, prostate cancer, ovarian cancer, hepatocellular carcinoma, pancreatic cancer, kidney cancer, stomach cancer, colorectal cancer, lung cancer and the like.
Discovery of LY3325656: A GPR142 agonist suitable for clinical testing in human
Chen, Jiehao,Efanov, Alexander M.,Fang, Xiankang,Jiang, Yi,Jun Zhang, Xue,Li, Lei,Lin, Hua V.,Liu, Jia,Liu, Lian Zhu,Long Hu, Zhi,Ma, Tianwei,Thomas, Melissa K,Wang, Fan,Wang, Jingru,Xiao, Fei,Xu, Jianfeng,Zeng, Mi,Zhang, Lei,Zhen Zhang, Hai,Zhou, Jingye,Zou, Haixia,Zou, Zack
supporting information, (2020/01/28)
The discovery and optimization of a novel series of GPR142 agonists are described. These led to the identification of compound 21 (LY3325656), which demonstrated anti-diabetic benefits in pre-clinical studies and ADME/PK properties suitable for human dosing. Compound 21 is the first GPR142 agonist molecule advancing to phase 1 clinic trials for the treatment of Type 2 diabetes.
Discovery of AZD4573, a Potent and Selective Inhibitor of CDK9 That Enables Short Duration of Target Engagement for the Treatment of Hematological Malignancies
Barlaam, Bernard,Casella, Robert,Cidado, Justin,Cook, Calum,De Savi, Chris,Dishington, Allan,Donald, Craig S.,Drew, Lisa,Ferguson, Andrew D.,Ferguson, Douglas,Glossop, Steve,Grebe, Tyler,Gu, Chungang,Hande, Sudhir,Hawkins, Janet,Hird, Alexander W.,Holmes, Jane,Horstick, James,Jiang, Yun,Lamb, Michelle L.,McGuire, Thomas M.,Moore, Jane E.,O'Connell, Nichole,Pike, Andy,Pike, Kurt G.,Proia, Theresa,Roberts, Bryan,San Martin, Maryann,Sarkar, Ujjal,Shao, Wenlin,Stead, Darren,Sumner, Neil,Thakur, Kumar,Vasbinder, Melissa M.,Varnes, Jeffrey G.,Wang, Jianyan,Wang, Lei,Wu, Dedong,Wu, Liangwei,Yang, Bin,Yao, Tieguang
supporting information, p. 15564 - 15590 (2021/01/09)
A CDK9 inhibitor having short target engagement would enable a reduction of Mcl-1 activity, resulting in apoptosis in cancer cells dependent on Mcl-1 for survival. We report the optimization of a series of amidopyridines (from compound 2), focusing on properties suitable for achieving short target engagement after intravenous administration. By increasing potency and human metabolic clearance, we identified compound 24, a potent and selective CDK9 inhibitor with suitable predicted human pharmacokinetic properties to deliver transient inhibition of CDK9. Furthermore, the solubility of 24 was considered adequate to allow i.v. formulation at the anticipated effective dose. Short-term treatment with compound 24 led to a rapid dose- and time-dependent decrease of pSer2-RNAP2 and Mcl-1, resulting in cell apoptosis in multiple hematological cancer cell lines. Intermittent dosing of compound 24 demonstrated efficacy in xenograft models derived from multiple hematological tumors. Compound 24 is currently in clinical trials for the treatment of hematological malignancies.
PYRAZOLYL COMPOUNDS AND METHODS OF USE THEREOF
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Paragraph 0374-0379; 0192-0193; 0532-0535, (2020/05/14)
Compounds having activity as chemotherapeutic agents are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, stereoisomer, isotopic form or prodrug thereof, wherein R1a, R1b, R1c, R1d, L, and are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods for treating cancer (e.g., hematological cancers) are also provided.
PYRROLOPYRIMIDINES FOR USE IN INFLUENZA VIRUS INFECTION
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Paragraph 0101-0102, (2017/09/20)
The invention relates to compounds having the structure of formula (I) which can be used for the treatment of or against influenza infections.
ISOXAZOLE DERIVATIVES FOR USE IN THE TREATMENT OF PULMONARY DISEASES AND DISORDERS
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Paragraph 0583, (2017/03/21)
The present disclosure features disclosed method of treating disorders such as COPD, bronchitis and/or asthma using disclosed compounds, optionally together with one or more additional active agents. Contemplated methods include administrating orally or by inhalation to a patient one or more disclosed compounds.
ANTI-INFECTIVE HETEROCYCLIC COMPOUNDS AND USES THEREOF
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Page/Page column 9; 137; 138, (2018/04/11)
The present invention relates to heterocyclic compounds of Formula I useful as anti-infective agents. The present invention further relates to a method of treating an infection by administering such compounds, and to pharmaceutical compositions comprising such compounds.
Chemical Compounds
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Paragraph 0572, (2017/01/19)
Provided are a series of novel pyridine or pyrimidine derivatives which inhibit CDK9 and may be useful for the treatment of hyperproliferative diseases. In particular the compounds are of use in the treatment of proliferative disease such as cancer including hematological malignancies such as acute myeloid leukemia, multiple myeloma, chronic lymphocytic leukemia, diffuse large B cell lymphoma, Burkitt's lymphoma, follicular lymphoma and solid tumors such as breast cancer, lung cancer, neuroblastoma and colon cancer.
Enantioselective preparation of 3-Arylcycloalkylamines by rhodium-catalyzed 1,4-addition and subsequent stereodivergent reduction
Gebhardt, Sandra,Müller, Christian H.,Westmeier, Johannes,Harms, Klaus,Von Zezschwitz, Paultheo
, p. 507 - 514 (2015/03/05)
N-Sulfonylimines of cycloalk-2-enones are well-suited for the enantioselective rhodium(I)/ binap-catalyzed 1,4-additions of arylzinc halides. The cyclic enamides, obtained after quenching, are sensitive towards chromatography, but can undergo diastereosel
COMPOUNDS, COMPOSITIONS AND METHODS OF INCREASING CFTR ACTIVITY
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Paragraph 0634, (2016/02/24)
The present disclosure features disclosed compounds which can increase cystic fibrosis transmembrane conductance regulator (CFTR) activity as measured in human bronchial epithelial (hBE) cells. The present disclosure also features methods of treating a condition associated with decreased CFTR activity or a condition associated with a dysfunction of proteostasis comprising administering to a subject an effective amount of a disclosed compound.
