817166-73-7Relevant academic research and scientific papers
High-Fidelity Sequence-Selective Duplex Formation by Recognition-Encoded Melamine Oligomers
Ballester, Pablo,Bolgar, Peter,Hunter, Christopher A.,Troselj, Pavle
, p. 8669 - 8678 (2021/06/28)
Melamine oligomers composed of repeating triazine-piperidine units and equipped with phenol and phosphine oxide side-chains form H-bonded duplexes. The melamine backbone provides sufficient rigidity to prevent intramolecular folding of oligomers up to thr
Trisubstituted Imidazoles with a Rigidized Hinge Binding Motif Act As Single Digit nM Inhibitors of Clinically Relevant EGFR L858R/T790M and L858R/T790M/C797S Mutants: An Example of Target Hopping
Juchum, Michael,Günther, Marcel,D?ring, Eva,Sievers-Engler, Adrian,L?mmerhofer, Michael,Laufer, Stefan
supporting information, p. 4636 - 4656 (2017/06/13)
The high genomic instability of non-small cell lung cancer tumors leads to the rapid development of resistance against promising EGFR tyrosine kinase inhibitors (TKIs). A recently detected triple mutation compromises the activity of the gold standard third-generation EGFR inhibitors. We have prepared a set of trisubstituted imidazoles with a rigidized 7-azaindole hinge binding motif as a new structural class of EGFR inhibitors by a target hopping approach from p38α MAPK inhibitor templates. On the basis of an iterative approach of docking, compound preparation, biological testing, and SAR interpretation, robust and flexible synthetic routes were established. As a result, we report two reversible inhibitors 11d and 11e of the clinically challenging triple mutant L858R/T790M/C797S with IC50 values in the low nanomolar range. Furthermore, we developed a kinome selective irreversible inhibitor 45a with an IC50 value of 1 nM against the EGFR L858R/T790M double mutant. Target binding kinetics and metabolic stability data are included. These potent mutant EGFR inhibitors may serve as a basis for the development of structurally novel EGFR probes, tools, or candidates.
Synthesis of the tripeptide domain of sanglifehrins using asymmetric phase-transfer catalysis
White, James D.,Suttisintong, Khomson
, p. 2757 - 2762 (2013/04/23)
The tripeptide (S)-valinyl-(S)-m-hydroxyphenylalanyl-(3S)-piperazate common to immunosuppressant sanglifehrins was synthesized from the constituent amino acid residues in nine steps and 42% overall yield. A key construction was the installation of (S) absolute configuration in m-hydroxyphenylalanine using asymmetric phase-transfer catalysis in the presence of N-(1-naphthyl) cinchonidinium bromide. Cbz-protected (S)-valine was first coupled to the amino group of (S)-m-triisopropylsilyloxyphenylalanine tert-butyl ester, and the resulting dipeptide after ester cleavage was linked to (3S)-methyl piperazate.
Selective Mg insertion into substituted mono- and dichloro arenes in the presence of LiCl: A new preparation of boscalid
Dunst, Cora,Knochel, Paul
experimental part, p. 2064 - 2068 (2011/10/09)
The LiCl-mediated Mg insertion into polysubstituted aryl chlorides bearing up to three chloro substituents in ortho or meta position selectively leads to Grignard reagents which readily react with various electrophiles. As an application, we have developed a new formal synthesis of boscalid. Georg Thieme Verlag Stuttgart - New York.
From solution-phase to solid-phase enyne metathesis: Crossover in the relative performance of two commonly used ruthenium pre-catalysts
Brittain, Dominic E.A.,Lawrence Gray,Schreiber, Stuart L.
, p. 5086 - 5093 (2007/10/03)
A crossover in the ability of two distinct ruthenium-based metathesis pre-catalysts to effect the synthesis of dialkenylboronic esters in solution and on the solid-phase was observed. Specifically, while the Grubbs 2nd generation pre-catalyst 3 affords a
Method for the rapid synthesis of highly functionalized 2-hydroxy-1-naphthoates. Syntheses of the naphthoic acid components of neocarzinostatin chromophore and N1999A2
Ji, Nan,Rosen, Brad M.,Myers, Andrew G.
, p. 4551 - 4553 (2007/10/03)
(Chemical equation presented) We describe a four-step sequence for the synthesis of complex 2-hydroxy-1-naphthoic acids involving Z-selective olefination of benzaldehyde derivatives with a novel dioxolenone-containing phenyl phosphonate reagent, followed
