Statistical Molecular Design: A Tool to Follow Up Hits from Small-Molecule Screening

2013 ◽  
pp. 169-188
Author(s):  
Anders E. G. Lindgren ◽  
Andreas Larsson ◽  
Anna Linusson ◽  
Mikael Elofsson
Keyword(s):  
Small Molecule ◽  
Molecular Design ◽  
Small Molecule Screening ◽  
Statistical Molecular Design

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.

The Effect of Donor Molecular Structure on Power Conversion Efficiency of Small-Molecule-Based Organic Solar Cells

2019 ◽  
Vol 16 (3) ◽  
pp. 236-243 ◽  
Author(s):  
Hui Zhang ◽  
Yibing Ma ◽  
Youyi Sun ◽  
Jialei Liu ◽  
Yaqing Liu ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Solar Cells ◽  
Power Conversion Efficiency ◽  
Conversion Efficiency ◽  
Small Molecule ◽  
Organic Solar Cells ◽  
Molecular Design ◽  
Power Conversion ◽  
The Relationship

In this review, small-molecule donors for application in organic solar cells reported in the last three years are highlighted. Especially, the effect of donor molecular structure on power conversion efficiency of organic solar cells is reported in detail. Furthermore, the mechanism is proposed and discussed for explaining the relationship between structure and power conversion efficiency. These results and discussions draw some rules for rational donor molecular design, which is very important for further improving the power conversion efficiency of organic solar cells based on the small-molecule donor.

scholarly journals Enabling rapid COVID-19 small molecule drug design through scalable deep learning of generative models

2021 ◽  
pp. 109434202110109
Author(s):  
Sam Ade Jacobs ◽  
Tim Moon ◽  
Kevin McLoughlin ◽  
Derek Jones ◽  
David Hysom ◽  
...  
Keyword(s):  
Small Molecule ◽  
Molecular Design ◽  
Turnaround Time ◽  
Generative Models ◽  
Quality Model ◽  
Training Time ◽  
Small Molecule Drug ◽  
Training Approach ◽  
Previous State ◽  
Multi Level

We improved the quality and reduced the time to produce machine learned models for use in small molecule antiviral design. Our globally asynchronous multi-level parallel training approach strong scales to all of Sierra with up to 97.7% efficiency. We trained a novel, character-based Wasserstein autoencoder that produces a higher quality model trained on 1.613 billion compounds in 23 minutes while the previous state of the art takes a day on 1 million compounds. Reducing training time from a day to minutes shifts the model creation bottleneck from computer job turnaround time to human innovation time. Our implementation achieves 318 PFLOPs for 17.1% of half-precision peak. We will incorporate this model into our molecular design loop enabling the generation of more diverse compounds; searching for novel, candidate antiviral drugs improves and reduces the time to synthesize compounds to be tested in the lab.

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.

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
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