947667-22-3Relevant articles and documents
Structure-Guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) Inhibitors
Liu, Shuai,Yosief, Hailemichael O.,Dai, Lingling,Huang, He,Dhawan, Gagan,Zhang, Xiaofeng,Muthengi, Alex M.,Roberts, Justin,Buckley, Dennis L.,Perry, Jennifer A.,Wu, Lei,Bradner, James E.,Qi, Jun,Zhang, Wei
, p. 7785 - 7795 (2018/09/13)
The simultaneous inhibition of polo-like kinase 1 (PLK1) and BRD4 bromodomain by a single molecule could lead to the development of an effective therapeutic strategy for a variety of diseases in which PLK1 and BRD4 are implicated. Compound 23 has been found to be a potent dual kinase-bromodomain inhibitor (BRD4-BD1 IC50 = 28 nM, PLK1 IC50 = 40 nM). Compound 6 was found to be the most selective PLK1 inhibitor over BRD4 in our series (BRD4-BD1 IC50 = 2579 nM, PLK1 IC50 = 9.9 nM). Molecular docking studies with 23 and BRD4-BD1/PLK1 as well as with 6 corroborate the biochemical assay results.
Design and synthesis of highly selective, orally active Polo-like kinase-2 (Plk-2) inhibitors
Bowers, Simeon,Truong, Anh P.,Ye, Michael,Aubele, Danielle L.,Sealy, Jennifer M.,Neitz, R. Jeffrey,Hom, Roy K.,Chan, Wayman,Dappen, Michael S.,Galemmo Jr., Robert A.,Konradi, Andrei W.,Sham, Hing L.,Zhu, Yong L.,Beroza, Paul,Tonn, George,Zhang, Heather,Hoffman, Jennifer,Motter, Ruth,Fauss, Donald,Tanaka, Pearl,Bova, Michael P.,Ren, Zhao,Tam, Danny,Ruslim, Lany,Baker, Jeanne,Pandya, Deepal,Diep, Linnea,Fitzgerald, Kent,Artis, Dean R.,Anderson, John P.,Bergeron, Marcelle
, p. 2743 - 2749 (2013/07/19)
Polo-like kinase-2 (Plk-2) is a potential therapeutic target for Parkinson's disease and this Letter describes the SAR of a series of dihydropteridinone based Plk-2 inhibitors. By optimizing both the N-8 substituent and the biaryl region of the inhibitors we obtained single digit nanomolar compounds such as 37 with excellent selectivity for Plk-2 over Plk-1. When dosed orally in rats, compound 37 demonstrated a 41-45% reduction of pS129-α-synuclein levels in the cerebral cortex.
DIHYDROPTERIDINONE DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF
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Page/Page column 58-59, (2012/07/28)
Dihydroperidinone derivatives, preparation process and pharmaceutical use thereof are disclosed. Specially, new dihydroperidinone derivatives represented by general formula (I), wherein each substituent of the general formula (I) is defined as in the description, their preparation process, pharmaceutical compositions comprising said derivatives and their use as therapeutical agents, especially as Plk kinase inhibitors are disclosed.
