109277-82-9Relevant articles and documents
Discovery of AZD9833, a Potent and Orally Bioavailable Selective Estrogen Receptor Degrader and Antagonist
Scott, James S.,Moss, Thomas A.,Balazs, Amber,Barlaam, Bernard,Breed, Jason,Carbajo, Rodrigo J.,Chiarparin, Elisabetta,Davey, Paul R. J.,Delpuech, Oona,Fawell, Stephen,Fisher, David I.,Gagrica, Sladjana,Gangl, Eric T.,Grebe, Tyler,Greenwood, Ryan D.,Hande, Sudhir,Hatoum-Mokdad, Holia,Herlihy, Kara,Hughes, Samantha,Hunt, Thomas A.,Huynh, Hoan,Janbon, Sophie L. M.,Johnson, Tony,Kavanagh, Stefan,Klinowska, Teresa,Lawson, Mandy,Lister, Andrew S.,Marden, Stacey,McGinnity, Dermot F.,Morrow, Christopher J.,Nissink, J. Willem M.,O'Donovan, Daniel H.,Peng, Bo,Polanski, Radoslaw,Stead, Darren S.,Stokes, Stephen,Thakur, Kumar,Throner, Scott R.,Tucker, Michael J.,Varnes, Jeffrey,Wang, Haixia,Wilson, David M.,Wu, Dedong,Wu, Ye,Yang, Bin,Yang, Wenzhan
, p. 14530 - 14559 (2020)
Herein we report the optimization of a series of tricyclic indazoles as selective estrogen receptor degraders (SERD) and antagonists for the treatment of ER+breast cancer. Structure based design together with systematic investigation of each region of the molecular architecture led to the identification of N-[1-(3-fluoropropyl)azetidin-3-yl]-6-[(6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl]pyridin-3-amine (28). This compound was demonstrated to be a highly potent SERD that showed a pharmacological profile comparable to fulvestrant in its ability to degrade ERα in both MCF-7 and CAMA-1 cell lines. A stringent control of lipophilicity ensured that 28 had favorable physicochemical and preclinical pharmacokinetic properties for oral administration. This, combined with demonstration of potent in vivo activity in mouse xenograft models, resulted in progression of this compound, also known as AZD9833, into clinical trials.
Ruthenium-Catalyzed Dehydrogenative N-Heterocyclization: Indoles from 2-Aminophenethyl Alcohols and 2-Nitrophenethyl Alcohols
Tsuji, Yasushi,Kotachi, Shinji,Huh, Keun-Tae,Watanabe, Yoshihisa
, p. 580 - 584 (2007/10/02)
Indole derivatives 3 were readily obtained from 2-aminophenethyl alcohols 1 in the presence of 2 mol percent (based on 1) of RuCl2(PPh3)3 under reflux in toluene.Indole (3a) was afforded from 2-aminophenethyl alcohol (1a) quantitatively.Other indoles (3) were also obtained in 73-99percent isolated yields from the corresponding 1, which were easily prepared by condensation between the corresponding 2-nitrotoluenes and aldehydes followed by reduction.During the reaction, a stoichiometric amount of hydrogen was spontaneously evolved into the gas phase.With a heterogeneous and homogeneous binary catalyst system, indoles were afforded in one pot from 2-nitrophenethyl alcohols 2 under a hydrogen atmosphere.
