P031 The last 10%: small molecule screening for correctors of rare CFTRprocessing mutations

2021 ◽  
Vol 20 ◽  
pp. S48
Author(s):  
M. Ensinck ◽  
L. De Keersmaecker ◽  
M. Nijs ◽  
A.S. Ramalho ◽  
K. De Boeck ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Screening

Synthesis of Elaborate Benzofuran-2-Carboxamide Derivatives Through a Combination of 8-Aminoquinoline Directed C–H Arylations and Transamidations

2019 ◽  
Author(s):  
Michael Oschmann ◽  
Linus Johansson Holm ◽  
Oscar Verho
Keyword(s):  
Small Molecule ◽  
High Efficiency ◽  
Synthetic Strategy ◽  
Small Molecule Screening ◽  
Physiological Properties ◽  
Wide Range ◽  
Directing Group ◽  
Synthetic Sequence

Benzofurans are everywhere in nature and they have been extensively studied by medicinal chemists over the years because of their chemotherapeutic and physiological properties. Herein, we describe a strategy that can be used to access elaborate benzo-2-carboxamide derivatives, which involves a synthetic sequence of 8-aminoquinoline directed C–H arylations followed by transamidations. For the directed C–H arylations, Pd catalysis was used to install a wide range of aryl and heteroaryl substituents at the C3 position of the benzofuran scaffold in high efficiency. Directing group cleavage and further diversification of the C3-arylated benzofuran products were then achieved in a single synthetic operation through the utilization of a two-step transamidation protocol. By bocylating the 8-aminoquinoline amide moiety of these products, it proved possible to activate them towards aminolysis with different amine nucleophiles. Interestingly, this aminolysis reaction was found to proceed efficiently without the need of any additional catalyst or additive. Given the high efficiency and modularity of this synthetic strategy, it constitute a very attractive approach for generating structurally-diverse collections of benzofuran derivatives for small molecule screening.

Towards drugging the ‘undruggable’: enhancing the scaffold diversity of synthetic small molecule screening collections using diversity-oriented synthesis

2013 ◽  
Vol 1 (1) ◽  
Author(s):  
Warren R.J.D. Galloway ◽  
David R. Spring
Keyword(s):  
Small Molecule ◽  
Structural Diversity ◽  
Library Size ◽  
Diversity Oriented Synthesis ◽  
Biological Targets ◽  
Small Molecule Screening ◽  
Chemistry Research ◽  
Large Numbers ◽  
Small Molecule Libraries ◽  
Scaffold Diversity

AbstractMedicinal chemistry research has traditionally focused upon a limited set of biological targets. Many other human disease-related targets have been termed ‘undruggable’ as they have proved largely impervious to modulation by small molecules. However, it is becoming increasingly evident that such targets can indeed be modulated; they are simply being challenged with the wrong types of molecules. Traditionally, screening libraries were composed of large numbers of structurally similar compounds. However, library size is not everything; the structural diversity of the library, which is largely dictated by the range of molecular scaffolds present, is crucial. Diversity-oriented synthesis (DOS) generates small molecule libraries with high levels of scaffold, and thus structural, diversity. Such collections should provide hits against a broad range of targets with high frequency, including ‘undruggable’ targets. Examples in the area of scaffold diversity generation taken from the author’s laboratories are given.

Monitoring Signaling by the p75NTR Receptor Utilizing a Caspase-3 Activation Assay Amenable to Small-Molecule Screening

2012 ◽  
Vol 10 (4) ◽  
pp. 353-364
Author(s):  
J. Michael Bradshaw ◽  
Lan Nguyen ◽  
William Wallace ◽  
Calvin Li ◽  
John-Michael Sauer ◽  
...  
Keyword(s):  
Small Molecule ◽  
Caspase 3 ◽  
Small Molecule Screening ◽  
Activation Assay

Back to Basics: Label-Free Technologies for Small Molecule Screening

2008 ◽  
Vol 11 (3) ◽  
pp. 231-237 ◽  
Author(s):  
Andrew Shiau ◽  
Mark Massari ◽  
Can Ozbal
Keyword(s):  
Small Molecule ◽  
Label Free ◽  
Small Molecule Screening

scholarly journals Small-Molecule Screening Identifies Modulators of Aquaporin-2 Trafficking

2013 ◽  
Vol 24 (5) ◽  
pp. 744-758 ◽  
Author(s):  
Jana Bogum ◽  
Dörte Faust ◽  
Kerstin Zühlke ◽  
Jenny Eichhorst ◽  
Marie C. Moutty ◽  
...  
Keyword(s):  
Small Molecule ◽  
Aquaporin 2 ◽  
Small Molecule Screening
Sign in / Sign up

Export Citation Format

Share Document