123762-08-3Relevant academic research and scientific papers
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.
Fragment-Guided Discovery of Pyrazole Carboxylic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2 Related Factor 2 (KEAP1:NRF2) Protein-Protein Interaction
Norton, David,Bonnette, William G.,Callahan, James F.,Carr, Maria G.,Griffiths-Jones, Charlotte M.,Heightman, Tom D.,Kerns, Jeffrey K.,Nie, Hong,Rich, Sharna J.,Richardson, Caroline,Rumsey, William,Sanchez, Yolanda,Verdonk, Marcel L.,Willems, Henri?tte M. G.,Wixted, William E.,Wolfe, Lawrence,Woolford, Alison J.-A.,Wu, Zining,Davies, Thomas G.
, p. 15949 - 15972 (2021/11/16)
The NRF2-mediated cytoprotective response is central to cellular homoeostasis, and there is increasing interest in developing small-molecule activators of this pathway as therapeutics for diseases involving chronic oxidative stress. The protein KEAP1, which regulates NRF2, is a key point for pharmacological intervention, and we recently described the use of fragment-based drug discovery to develop a tool compound that directly disrupts the protein-protein interaction between NRF2 and KEAP1. We now present the identification of a second, chemically distinct series of KEAP1 inhibitors, which provided an alternative chemotype for lead optimization. Pharmacophoric information from our original fragment screen was used to identify new hit matter through database searching and to evolve this into a new lead with high target affinity and cell-based activity. We highlight how knowledge obtained from fragment-based approaches can be used to focus additional screening campaigns in order to de-risk projects through the rapid identification of novel chemical series.
A Comparative Assessment Study of Known Small-Molecule Keap1-Nrf2 Protein-Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity
Tran, Kim T.,Pallesen, Jakob S.,Solbak, Sara M.,Narayanan, Dilip,Baig, Amina,Zang, Jie,Aguayo-Orozco, Alejandro,Carmona, Rosa M. C.,Garcia, Anthony D.,Bach, Anders
, p. 8028 - 8052 (2019/10/11)
Inhibiting the protein-protein interaction (PPI) between the transcription factor Nrf2 and its repressor protein Keap1 has emerged as a promising strategy to target oxidative stress in diseases, including central nervous system (CNS) disorders. Numerous non-covalent small-molecule Keap1-Nrf2 PPI inhibitors have been reported to date, but many feature suboptimal physicochemical properties for permeating the blood-brain barrier, while others contain problematic structural moieties. Here, we present the first side-by-side assessment of all reported Keap1-Nrf2 PPI inhibitor classes using fluorescence polarization, thermal shift assay, and surface plasmon resonance - and further evaluate the compounds in an NQO1 induction cell assay and in counter tests for nonspecific activities. Surprisingly, half of the compounds were inactive or deviated substantially from reported activities, while we confirm the cross-assay activities for others. Through this study, we have identified the most promising Keap1-Nrf2 inhibitors that can serve as pharmacological probes or starting points for developing CNS-active Keap1 inhibitors.
DIHYDROPYRIMIDINE DERIVATIVES AND USES THEREOF IN THE TREATMENT OF HBV INFECTION OR OF HBV-INDUCED DISEASES
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Page/Page column 61, (2019/11/28)
Provided herein are dihydropyrimidine derivatives which are useful in the treatment of HBV infection or HBV-induced diseases, as well as pharmaceutical or medical applications thereof.
ARYLCYCLOHEXYL PYRAZOLES AS NRF2 REGULATORS
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Page/Page column 77, (2017/05/07)
The present invention relates to arylcyclohexyl pyrazole compounds, methods of making them, pharmaceutical compositions containing them and their use as NRF2 regulators.
NOVEL CYCLIC BENZIMIDAZOLE DERIVATIVES USEFUL ANTI-DIABETIC AGENTS
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Page/Page column 70; 71, (2011/09/30)
Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK- activated protein kinase. The compounds of the present invention are useful in
Modulators of 11- beta hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same
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Page/Page column 42, (2010/11/28)
The present invention relates to inhibitors of 11-β hydroxyl steroid dehydrogenase type 1 and pharmaceutical compositions thereof. The compounds of the invention can be useful in the treatment of various diseases associated with expression or activity of 11-β hydroxyl steroid dehydrogenase type 1.
BIS(TRIFLUOROACETYLACETONATO)COBALT(II) CATALYZED OXIDATION-REDUCTION HYDRATION OF OLEFINS SELECTIVE FORMATION OF ALCOHOLS FROM OLEFINS
Inoki, Satoshi,Kato, Koji,Takai, Toshihiro,Isayama, Shigeru,Yamada, Tohru,Mukaiyama, Teruaki
, p. 515 - 518 (2007/10/02)
Various olefins are hydrated with molecular oxygen (oxidant) and a secondary alcohol (reductant) in the presence of a catalytic amount of bis(trifluoroacetylacetonato)cobalt(II) in good yields
