4 research outputs found
Novel Catalyst System for Suzuki-Miyaura Coupling of Challenging DNA-Linked Aryl Chlorides
A novel Pd catalyst
system, [(<i>t</i>-Bu)<sub>2</sub>PÂ(OH)]<sub>2</sub>PdCl<sub>2</sub> (POPd) with the ligand sodium
2′-(dicyclohexylphosphino)-2,6-dimethoxy-[1,1′-biphenyl]-3-sulfonate,
is reported. It effectively catalyzes the Suzuki-Miyaura coupling
of challenging phenyl chlorides and pyrimidinyl chlorides that are
covalently linked to a double-stranded DNA-template with various boronic
acids/esters
Development and Synthesis of DNA-Encoded Benzimidazole Library
Encoded library technology
(ELT) is an effective approach to the
discovery of novel small-molecule ligands for biological targets.
A key factor for the success of the technology is the chemical diversity
of the libraries. Here we report the development of DNA-conjugated
benzimidazoles. Using 4-fluoro-3-nitrobenzoic acid as a key synthon,
we synthesized a 320 million-member DNA-encoded benzimidazole library
using Fmoc-protected amino acids, amines and aldehydes as diversity
elements. Affinity selection of the library led to the discovery of
a novel, potent and specific antagonist of the NK3 receptor
Design and Synthesis of Biaryl DNA-Encoded Libraries
DNA-encoded
library technology (ELT) is a powerful tool for the
discovery of new small-molecule ligands to various protein targets.
Here we report the design and synthesis of biaryl DNA-encoded libraries
based on the scaffold of 5-formyl 3-iodobenzoic acid. Three reactions
on DNA template, acylation, Suzuki–Miyaura coupling and reductive
amination, were applied in the library synthesis. The three cycle
library of 3.5 million diversity has delivered potent hits for phosphoinositide
3-kinase α (PI3Kα)
Discovery of a Potent Class of PI3Kα Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT)
In the search of PI3K p110α
wild type and H1047R mutant selective small molecule leads, an encoded
library technology (ELT) campaign against the desired target proteins
was performed which led to the discovery of a selective chemotype
for PI3K isoforms from a three-cycle DNA encoded library. An X-ray
crystal structure of a representative inhibitor from this chemotype
demonstrated a unique binding mode in the p110α protein