Wehn, Paul M.; Rizzi, James P.; Dixon, Darryl D.; Grina, Jonas A.; Schlachter, Stephen T.; Wang, Bin; Xu, Rui; Yang, Hanbiao; Du, Xinlin; Han, Guangzhou; Wang, Keshi; Cao, Zhaodan; Cheng, Tzuling; Czerwinski, Robert M.; Goggin, Barry S.; Huang, Heli; Halfmann, Megan M.; Maddie, Melissa A.; Morton, Emily L.; Olive, Sarah R.; Tan, Huiling; Xie, Shanhai; Wong, Tai; Josey, John A.; Wallace, Eli M. published the article 《Design and Activity of Specific Hypoxia-Inducible Factor-2α (HIF-2α) Inhibitors for the Treatment of Clear Cell Renal Cell Carcinoma: Discovery of Clinical Candidate (S)-3-((2,2-Difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl)oxy)-5-fluorobenzonitrile (PT2385)》. Keywords: indene preparation HIF2 inhibitor renal cell carcinoma treatment.They researched the compound: (1,10-Phenanthroline)(trifluoromethyl)copper(I)( cas:1300746-79-5 ).Electric Literature of C13H8CuF3N2. Aromatic heterocyclic compounds can be divided into two categories: single heterocyclic and fused heterocyclic. In addition, there is a lot of other information about this compound (cas:1300746-79-5) here.
HIF-2α, a member of the HIF family of transcription factors, is a key oncogenic driver in cancers such as clear cell renal cell carcinoma (ccRCC). A signature feature of these cancers is the overaccumulation of HIF-2α protein, often by inactivation of the E3 ligase VHL (von Hippel-Lindau). Herein the authors disclose their structure based drug design (SBDD) approach that culminated in the identification of PT2385, the first HIF-2α antagonist to enter clin. trials. Highlights include the use of a putative n → π*Ar interaction to guide early analog design, the conformational restriction of an essential hydroxyl moiety, and the remarkable impact of fluorination near the hydroxyl group. Evaluation of select compounds from two structural classes in a sequence of PK/PD, efficacy, PK, and metabolite profiling identified I (PT2385, luciferase EC50 = 27 nM) as the clin. candidate. Finally, a retrospective crystallog. anal. describes the structural perturbations necessary for efficient antagonism.
This compound((1,10-Phenanthroline)(trifluoromethyl)copper(I))Electric Literature of C13H8CuF3N2 was discussed at the molecular level, the effects of temperature and reaction time on the properties of the compound were discussed, and the optimum reaction conditions were selected.
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