760-58-7Relevant articles and documents
Design, synthesis, and biological evaluation of quinazoline derivatives with covalent reversible warheads as potential FGFR4 inhibitors
Che, Jinxin,Dong, Xiaowu,Du, Jiaming,Gao, Jian,He, Qiaojun,Lu, Yang,Luo, Mengxin,Luo, Peihua,Nie, Wenwen,Pan, Chenghao,Wang, Jiao,Zhu, Hong
, (2022/03/16)
Fibroblast growth factor receptor 4 (FGFR4) together with co-receptors modulate the activation of downstream proteins that regulate fundamental processes, and elevated FGFR4 activity is associated with Hepatocellular Carcinoma (HCC). Hence, FGFR4 is a promising therapeutic target for HCC. Based on BLU9931, we designed and synthesized a series of phenylquinazoline derivatives as novel inhibitors of FGFR4 through the covalent reversible strategy. Among them, a novel compound (C3) showed FGFR4 and cell proliferation inhibitory activity. Cellular mechanism studies demonstrated that compound C3 induced apoptosis via the FGFR4 signaling pathway blockage. Further mechanism study showed that C3 has the reversible covalent binding capacity, could be used as a reference for the development of novel FGFR4 covalent reversible inhibitors.
IMMUNOPROTEASOME INHIBITORS
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Paragraph 0336; 0339; 0347; 0350, (2019/06/13)
Provided herein are compounds, such as a compound of Formula (I), or a pharmaceutically acceptable salt thereof, that are immunoproteasome (such as LMP2 and LMP7) inhibitors. The compounds described herein can be useful for the treatment of diseases treatable by inhibition of immunoproteasomes. Also provided herein are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
Evaluation of several routes to advanced pregabalin intermediates: Synthesis and enantioselective enzymatic reduction using ene-reductases
Debarge, Sebastien,McDaid, Paul,O'Neill, Pat,Frahill, James,Wong, John W.,Carr, Donncha,Burrell, Adam,Davies, Simon,Karmilowicz, Mike,Steflik, Jeremy
, p. 109 - 121 (2014/05/20)
This publication describes the evaluation of four synthetic routes to the advanced pregabalin (Lyrica) intermediate 7. Asymmetric reduction of (E)-7 with an ene-reductase (OPR1 from Lycopersicon esculentum) gave a saturated cyanoester intermediate 5 with the desired S stereocenter in ≥99% ee. OPR1 also catalyzed the reduction of (Z)-7 to (S)-5, but with lower conversion and selectivity.
PYRAZOLOPYRIMIDINE COMPOUNDS AS KINASE INHIBITORS
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Page/Page column 52, (2014/03/26)
The present disclosure provides compounds of Formula (LA) and/ or pharmaceutically acceptable salts thereof that are tyrosine kinase inhibitors, in particular BTK, and are potentially useful for the treatment of diseases treatable by inhibition of ty r-osine kinases such as cancer, inflammatory diseases such as arthritis, and the like. Also provided are pharmaceutical compositions containing such compounds and/or pharmaceutically acceptable salts thereof and processes for preparing such compounds and p h ar-maceutically acceptable salts thereof
Rationalisation of the stereochemical outcome of ene-reductase-mediated bioreduction of α,β-difunctionalised alkenes
Brenna, Elisabetta,Crotti, Michele,Gatti, Francesco G.,Manfredi, Alessia,Monti, Daniela,Parmeggiani, Fabio,Pugliese, Andrea,Zampieri, Davila
, p. 67 - 72 (2014/02/14)
The OYE1-3-mediated reductions of some α,β-difunctionalised alkenes, showing on the double bond a nitrile and ester group, are submitted to a careful stereochemical analysis, in order to identify which of the two electron-withdrawing groups (EWGs) is resp
Nitrile as activating group in the asymmetric bioreduction of β-cyanoacrylic acids catalyzed by ene-reductases
Winkler, Christoph K.,Clay, Dorina,Turrini, Nikolaus G.,Lechner, Horst,Kroutil, Wolfgang,Davies, Simon,Debarge, Sebastien,O'Neill, Pat,Steflik, Jeremy,Karmilowicz, Mike,Wong, John W.,Faber, Kurt
supporting information, p. 1878 - 1882 (2014/06/09)
Asymmetric bioreduction of an (E)-β-cyano-2,4-dienoic acid derivative by ene-reductases allowed a shortened access to a precursor of pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid] possessing the desired configuration in up to 94% conversion and >99% ee. Deuterium labelling studies showed that the nitrile moiety was the preferred activating/anchor group in the active site of the enzyme over the carboxylic acid or the corresponding methyl ester.
PROCESS FOR THE PREPARATION OF ( S ) - 3 - CYANO - 5 - METHYLHEXANOIC ACID DERIVATIVES ADN OF PREGABALIN
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Page/Page column 22, (2012/03/26)
The invention provides a process for the manufacture of a compound of formula (I) using an enzyme catalysed reduction of a compound of formula (lla) or llb). Compounds of formula (I) are useful for preparing pregabalin.
