Catalyst-Directed Divergent Catalytic Approaches to Expand Structural and Functional Scaffold Diversity via Metallo-Enolcarbene Intermediates

ACS Catalysis ◽  
2021 ◽  
pp. 4712-4721
Author(s):  
Kuiyong Dong ◽  
Haifeng Zheng ◽  
Yongliang Su ◽  
Ahmad Humeidi ◽  
Hadi Arman ◽  
...  
Keyword(s):  
Scaffold Diversity

Synthesis and Screening of A DNA-Encoded Library of Non-Peptidic Macrocycles

2020 ◽  
Author(s):  
Eric Koesema ◽  
Animesh Roy ◽  
Nicholas G. Paciaroni ◽  
Thomas Kodadek
Keyword(s):  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Cell Permeability ◽  
Phase Synthesis ◽  
Protein Ligands ◽  
High Affinity ◽  
Scaffold Diversity

There is considerable interest in the development of libraries of non-peptidic macrocycles as a source of ligands for difficult targets. We report here the solid-phase synthesis of a DNA-encoded library of several hundred thousand thioether-linked macrocycles. The library was designed to be highly diverse with respect to backbone scaffold diversity and to minimize the number of amide N-H bonds, which compromise cell permeability. The utility of the library as a source of protein ligands is demonstrated through the isolation of compounds that bind streptavidin, a model target, with high affinity.

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.

scholarly journals iVS analysis to evaluate the impact of scaffold diversity in the binding to cellular targets relevant in cancer

2018 ◽  
Vol 34 (1) ◽  
pp. 44-50 ◽  
Author(s):  
Agostino Cilibrizzi ◽  
Giuseppe Floresta ◽  
Vincenzo Abbate ◽  
Maria Paola Giovannoni
Keyword(s):  
Cellular Targets ◽  
Scaffold Diversity ◽  
The Impact

scholarly journals ScaffoldGraph: an open-source library for the generation and analysis of molecular scaffold networks and scaffold trees

2020 ◽  
Vol 36 (12) ◽  
pp. 3930-3931 ◽  
Author(s):  
Oliver B Scott ◽  
A W Edith Chan
Keyword(s):  
Open Source ◽  
High Throughput Screening ◽  
Chemical Space ◽  
Diversity Analysis ◽  
Graph Analysis ◽  
Command Line ◽  
Molecular Scaffold ◽  
Large Sets ◽  
Command Line Tool ◽  
Scaffold Diversity

Abstract Summary ScaffoldGraph (SG) is an open-source Python library and command-line tool for the generation and analysis of molecular scaffold networks and trees, with the capability of processing large sets of input molecules. With the increase in high-throughput screening data, scaffold graphs have proven useful for the navigation and analysis of chemical space, being used for visualization, clustering, scaffold-diversity analysis and active-series identification. Built on RDKit and NetworkX, SG integrates scaffold graph analysis into the growing scientific/cheminformatics Python stack, increasing the flexibility and extendibility of the tool compared to existing software. Availability and implementation SG is freely available and released under the MIT licence at https://github.com/UCLCheminformatics/ScaffoldGraph.

ChemInform Abstract: Scaffold Diversity Synthesis and Its Application in Probe and Drug Discovery

ChemInform ◽  
2016 ◽  
Vol 47 (35) ◽  
Author(s):  
Miguel Garcia-Castro ◽  
Stefan Zimmermann ◽  
Muthukumar G. Sankar ◽  
Kamal Kumar
Keyword(s):  
Drug Discovery ◽  
Scaffold Diversity

Synthesis of Small Molecules with High Scaffold Diversity: Exploitation of Metathesis Cascades in Combination with Inter- and Intramolecular Diels-Alder Reactions

2010 ◽  
Vol 16 (31) ◽  
pp. 9563-9571 ◽  
Author(s):  
Catherine O'Leary-Steele ◽  
Palle J. Pedersen ◽  
Thomas James ◽  
Thomas Lanyon-Hogg ◽  
Stuart Leach ◽  
...  
Keyword(s):  
Small Molecules ◽  
Diels Alder ◽  
Scaffold Diversity

Scaffold Diversity through Intramolecular Cascade Reactions of Solid-Supported CyclicN-Acyliminium Intermediates

2007 ◽  
Vol 9 (6) ◽  
pp. 1060-1072 ◽  
Author(s):  
Sebastian T. Le Quement ◽  
Thomas E. Nielsen ◽  
Morten Meldal
Keyword(s):  
Cascade Reactions ◽  
Scaffold Diversity

Scaffold diversity of natural products: inspiration for combinatorial library design

2008 ◽  
Vol 25 (5) ◽  
pp. 892 ◽  
Author(s):  
Kristina Grabowski ◽  
Karl-Heinz Baringhaus ◽  
Gisbert Schneider
Keyword(s):  
Natural Products ◽  
Combinatorial Library ◽  
Library Design ◽  
Scaffold Diversity ◽  
Combinatorial Library Design
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