321724-19-0Relevant articles and documents
Preparation method of XPO-1 inhibitor
-
Paragraph 0103-0105, (2022/01/12)
The invention provides a preparation method of an XPO-1 inhibitor. Specifically, a compound II is prepared from a compound I and pinacol diborate under the action of a Grignard reagent, then the compound II reacts with a compound III under the action of a catalyst and alkali to obtain a compound IV, the compound IV and a compound V are condensed and then hydrolysis is conducted to obtain a compound VI, and finally the final product Eltanexor is prepared through a mixed anhydride method. The preparation method has the advantages of simple and safe synthesis route and operation, easily available raw materials, simple post-treatment and high yield, and is suitable for industrial production.
A Monophosphine Ligand Derived from Anthracene Photodimer: Synthetic Applications for Palladium-Catalyzed Coupling Reactions
Wang, Xin,Liu, Wei-Gang,Tung, Chen-Ho,Wu, Li-Zhu,Cong, Huan
supporting information, p. 8158 - 8163 (2019/09/07)
Herein, we present an air-stable dianthracenyl monophosphine ligand (diAnthPhos) which can be prepared in two steps from commercially available anthracene derivatives. The ligand exhibits excellent efficiency for palladium-catalyzed coupling reactions. In particular, Miyaura borylation of heterocycle-containing electrophiles can be facilitated employing the diAnthPhos ligand with a broad substrate scope and low catalyst loading. The valuable synthetic utility of the new ligand is further demonstrated by a one-pot Miyaura borylation/Suzuki coupling protocol for heteroaryl-containing substrates.
Mitigation of Acetylcholine Esterase Activity in the 1,7-Diazacarbazole Series of Inhibitors of Checkpoint Kinase 1
Gazzard, Lewis,Williams, Karen,Chen, Huifen,Axford, Lorraine,Blackwood, Elizabeth,Burton, Brenda,Chapman, Kerry,Crackett, Peter,Drobnick, Joy,Ellwood, Charles,Epler, Jennifer,Flagella, Michael,Gancia, Emanuela,Gill, Matthew,Goodacre, Simon,Halladay, Jason,Hewitt, Joanne,Hunt, Hazel,Kintz, Samuel,Lyssikatos, Joseph,Macleod, Calum,Major, Sarah,Médard, Guillaume,Narukulla, Raman,Ramiscal, Judi,Schmidt, Stephen,Seward, Eileen,Wiesmann, Christian,Wu, Ping,Yee, Sharon,Yen, Ivana,Malek, Shiva
, p. 5053 - 5074 (2015/07/02)
Checkpoint kinase 1 (ChK1) plays a key role in the DNA damage response, facilitating cell-cycle arrest to provide sufficient time for lesion repair. This leads to the hypothesis that inhibition of ChK1 might enhance the effectiveness of DNA-damaging therapies in the treatment of cancer. Lead compound 1 (GNE-783), the prototype of the 1,7-diazacarbazole class of ChK1 inhibitors, was found to be a highly potent inhibitor of acetylcholine esterase (AChE) and unsuitable for development. A campaign of analogue synthesis established SAR delineating ChK1 and AChE activities and allowing identification of new leads with improved profiles. In silico docking using a model of AChE permitted rationalization of the observed SAR. Compounds 19 (GNE-900) and 30 (GNE-145) were identified as selective, orally bioavailable ChK1 inhibitors offering excellent in vitro potency with significantly reduced AChE activity. In combination with gemcitabine, these compounds demonstrate an in vivo pharmacodynamic effect and are efficacious in a mouse p53 mutant xenograft model.