34667-88-4Relevant articles and documents
Exploring the tetrahydroisoquinoline thiohydantoin scaffold blockade the androgen receptor as potent anti-prostate cancer agents
Xu, Xi,Ge, Raoling,Li, Lei,Wang, Jubo,Lu, Xiaoyu,Xue, Siqi,Chen, Xijing,Li, Zhiyu,Bian, Jinlei
, p. 1325 - 1344 (2017/11/13)
Prostate cancer (PC) is a major cause of cancer-related male death in worldwide and the identification of new and improved potent anti-PC molecules is constantly required. A novel scaffold of tetrahydroisoquinoline thiohydantoin was rationally designed based on the enzalutamide structures and our pre-work, leading to the discovery of a series of new antiproliferative compounds. Several new analogues displayed improved androgen receptor (AR) antagonistic activity, while maintaining the higher selective toxicity toward LNCaP cells (AR-rich) versus DU145 cells (AR-deficient) compared to enzalutamide. In fact, compound 55 exhibited promising in vitro antitumor activity by impairing AR unclear translocation. More importantly, 55 showed better pharmacokinetic properties compared to the compound 1 reported in our pre-work. These results demonstrate a step towards the development of novel and improved AR antagonists.
Irreversible inhibitors of tyrosine kinases
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Page column 70-71, (2008/06/13)
The present invention provides compounds that are irreversible inhibitors of tyrosine kinases. Also provided is a method of treating cancer, restenosis, atherosclerosis, endometriosis, and psoriasis and a pharmaceutical composition that comprises a compound that is an irreversible inhibitor of tyrosine kinases.
Synthesis of [1]Benzothieno[3,2-d]pyrimidines Substituted with Electron Donating Substituents on the Benzene Ring
Bridges, Alexander J.,Zhou, Hairong
, p. 1163 - 1172 (2007/10/03)
Various 2-fluorobenzonitriles were converted to the corresponding 3-amino[1]benzothiophenecarboxylic acid esters, which in turn were annulated with formamidine or various equivalents to produce the desired tricyclic benzothienopyrimidines. Various methoxy and nitro/amino substituants were placed on the phenyl ring, requiring several different strategies to prepare the desired benzothiophenes. Several different pyrimidone annulations were also required. The use of an electron rich 2-bromobenzonitrile in a four-step one-pot low temperature lithiation sequence to produce highly electron-rich amino[1]benzothiophenecarboxylate esters is also described. The synthesis of 7-amino-8-fluoro[1]benzothieno[3,2-d]pyrimid-4(3H)-one was relatively straightforward, but synthesis of the corresponding 7-amino-8-protio analogue proved to be very difficult, and required several approaches before a successful one was found.