Medicinal Chemistry Database GDBMedChem

10.26434/chemrxiv.7770809 ◽

2019 ◽

Author(s):

Mahendra Awale ◽

Finton Sirockin ◽

Nikolaus Stiefl ◽

Jean-Louis Reymond

Keyword(s):

Small Molecules ◽

Natural Product ◽

Medicinal Chemistry ◽

3D Visualization ◽

Molecular Size ◽

Similarity Searching ◽

Complex Molecules ◽

Synthetic Accessibility ◽

Simple Chemical ◽

Reduced Complexity

<div>The generated database GDB17 enumerates 166.4 billion possible molecules up to 17 atoms of C, N, O, S and halogens following simple chemical stability and synthetic feasibility rules, however medicinal chemistry criteria are not taken into account. Here we applied rules inspired by medicinal chemistry to exclude problematic functional groups and complex molecules from GDB17, and sampled the resulting subset evenly across molecular size, stereochemistry and polarity to form GDBMedChem as a compact collection of 10 million small molecules.</div><div><br></div><div>This collection has reduced complexity and better synthetic accessibility than the entire GDB17 but retains higher sp 3 - carbon fraction and natural product likeness scores compared to known drugs. GDBMedChem molecules are more diverse and very different from known molecules in terms of substructures and represent an unprecedented source of diversity for drug design. GDBMedChem is available for 3D-visualization, similarity searching and for download at http://gdb.unibe.ch.</div>

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Metal-Free Photoredox-Catalyzed C–H/C–H Coupling of Arenes Enabled by Interrupted Pummerer Activation

10.26434/chemrxiv.9158564 ◽

2019 ◽

Author(s):

Miles Aukland ◽

Mindaugas Šiaučiulis ◽

Adam West ◽

Gregory Perry ◽

David Procter

Keyword(s):

Natural Product ◽

Selective Reduction ◽

Cross Coupling ◽

One Pot ◽

Complex Molecules ◽

Pummerer Reaction ◽

Metal Free ◽

Bond Forming ◽

Coupling Partner ◽

Bioactive Natural Product

<p>Aryl–aryl cross-coupling constitutes one of the most widely used procedures for the synthesis of high-value materials, ranging from pharmaceuticals to organic electronics and conducting polymers. The assembly of (hetero)biaryl scaffolds generally requires multiple steps; coupling partners must be functionalized before the key bond-forming event is considered. Thus, the development of selective C–H arylation processes in arenes, that side-step the need for prefunctionalized partners, is crucial for streamlining the construction of these key architectures. Here we report an expedient, one-pot assembly of (hetero)biaryl motifs using photocatalysis and two non-prefunctionalized arene partners. The approach is underpinned by the activation of a C–H bond in an arene coupling partner using the interrupted Pummerer reaction. A unique pairing of the organic photoredox catalyst and the intermediate dibenzothiophenium salts enables highly selective reduction in the presence of sensitive functionalities. The utility of the metal-free, one-pot strategy is exemplified by the synthesis of a bioactive natural product and the modification of complex molecules of societal importance.</p>

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De Novo Drug Design Using Artificial Intelligence Applied on SARS-CoV-2 Viral Proteins ASYNT-GAN

BioChem ◽

10.3390/biochem1010004 ◽

2021 ◽

Vol 1 (1) ◽

pp. 36-48

Author(s):

Ivan Jacobs ◽

Manolis Maragoudakis

Keyword(s):

Deep Learning ◽

Small Molecules ◽

Natural Product ◽

De Novo ◽

Viral Proteins ◽

Computer Assisted ◽

De Novo Drug Design ◽

Learning Techniques ◽

Latent Space ◽

Synthetic Molecule

Computer-assisted de novo design of natural product mimetics offers a viable strategy to reduce synthetic efforts and obtain natural-product-inspired bioactive small molecules, but suffers from several limitations. Deep learning techniques can help address these shortcomings. We propose the generation of synthetic molecule structures that optimizes the binding affinity to a target. To achieve this, we leverage important advancements in deep learning. Our approach generalizes to systems beyond the source system and achieves the generation of complete structures that optimize the binding to a target unseen during training. Translating the input sub-systems into the latent space permits the ability to search for similar structures, and the sampling from the latent space for generation.

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Correlations between retention volume and molecular size parameters in gel permeation chromatography of small molecules

Australian Journal of Chemistry ◽

10.1071/ch9750189 ◽

1975 ◽

Vol 28 (1) ◽

pp. 189 ◽

Cited By ~ 4

Author(s):

RA Shanks

Keyword(s):

Molecular Weight ◽

Small Molecules ◽

Organic Molecules ◽

Retention Volume ◽

Molecular Size ◽

Gel Permeation Chromatography ◽

Molar Volumes ◽

Small Organic Molecules ◽

Molecular Dimension ◽

Gel Permeation

Gel permeation columns of Bio Beads S-X8 have been used to provide separation of oligomers and other small organic molecules. Results show successful separations up to molecular weight c. 600. The retention times of compounds have been correlated with the largest molecular dimension of the molecules and also with molar volumes.

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Recent Advances in Application of Biosensors in Tissue Engineering

BioMed Research International ◽

10.1155/2014/307519 ◽

2014 ◽

Vol 2014 ◽

pp. 1-18 ◽

Cited By ~ 56

Author(s):

Anwarul Hasan ◽

Md Nurunnabi ◽

Mahboob Morshed ◽

Arghya Paul ◽

Alessandro Polini ◽

...

Keyword(s):

Tissue Engineering ◽

Cell Culture ◽

Small Molecules ◽

Real Time ◽

Inflammatory Cytokines ◽

Serum Proteins ◽

Molecular Size ◽

Medical Diagnostics ◽

Alpha Fetoprotein ◽

Pharmaceutical Industries

Biosensors research is a fast growing field in which tens of thousands of papers have been published over the years, and the industry is now worth billions of dollars. The biosensor products have found their applications in numerous industries including food and beverages, agricultural, environmental, medical diagnostics, and pharmaceutical industries and many more. Even though numerous biosensors have been developed for detection of proteins, peptides, enzymes, and numerous other biomolecules for diverse applications, their applications in tissue engineering have remained limited. In recent years, there has been a growing interest in application of novel biosensors in cell culture and tissue engineering, for example, real-time detection of small molecules such as glucose, lactose, and H2O2as well as serum proteins of large molecular size, such as albumin and alpha-fetoprotein, and inflammatory cytokines, such as IFN-g and TNF-α. In this review, we provide an overview of the recent advancements in biosensors for tissue engineering applications.

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Anti-COVID drugs: repurposing existing drugs or search for new complex entities, strategies and perspectives

Future Medicinal Chemistry ◽

10.4155/fmc-2020-0204 ◽

2020 ◽

Vol 12 (19) ◽

pp. 1743-1757

Author(s):

Anna Pawełczyk ◽

Lucjusz Zaprutko

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Antiviral Activity ◽

Small Molecules ◽

Computational Chemistry ◽

Structural Modification ◽

Antiviral Agents ◽

Complex Molecules ◽

Active Complex ◽

Novel Virus ◽

Effective Drugs

At the end of 2019, a novel virus causing severe acute respiratory syndrome to spread globally. There are currently no effective drugs targeting SARS-CoV-2. In this study, based on the analysis of numerous references and selected methods of computational chemistry, the strategy of integrative structural modification of small molecules with antiviral activity into potential active complex molecules has been presented. Proposed molecules have been designed based on the structure of triterpene oleanolic acid and complemented by structures characteristic of selected anti-COVID therapy assisted drugs. Their pharmaceutical molecular parameters and the preliminary bioactivity were calculated and predicted. The results of the above analyses show that among the designed complex substances there are potential antiviral agents directed mainly on SARS-CoV-2.

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Asymmetric Synthesis of 3,3′-Piperidinoyl Spirooxindoles and Discovery of Stereospecific Cycloadducts as Novel Hedgehog Pathway Modulators

Synthesis ◽

10.1055/s-0040-1707222 ◽

2020 ◽

Vol 52 (21) ◽

pp. 3140-3152

Author(s):

Kamal Kumar ◽

Mohammad Rehan ◽

Jana Flegel ◽

Franziska Heitkamp ◽

Jorgelina L. Pergomet ◽

...

Keyword(s):

Transition Metal ◽

Small Molecules ◽

Asymmetric Synthesis ◽

Natural Product ◽

Transition Metal Complexes ◽

Alder Reaction ◽

Diels Alder ◽

Hedgehog Pathway ◽

Diels Alder Reaction ◽

Efficient Access

An enantioselective hetero-Diels–Alder reaction of alkylidene oxindoles and 2-aza-3-silyloxy-1,3-butadienes, catalyzed by divalent transition metal complexes with N,N′-dioxide ligands offered an efficient access to natural-product-based 3,3′-piperidinoyl spirooxindole class of small molecules. exo-Cycloadducts formed via stereospecific cycloaddition with Z-olefin displayed potent activity in modulation of hedgehog pathway.

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Intermolecular 3+3 Ring Expansion of Aziridines to Dehydropiperidines through the Intermediacy of Aziridinium Ylides

10.26434/chemrxiv.9961937.v1 ◽

2019 ◽

Author(s):

Jennifer Schomaker ◽

Josephine Eshon ◽

Kate A. Nicastri ◽

Steven C. Schmid ◽

William T. Raskopf ◽

...

Keyword(s):

Natural Product ◽

Functional Group ◽

Ring Expansion ◽

Sigmatropic Rearrangement ◽

Reactive Intermediate ◽

Mechanistic Studies ◽

Reaction Conditions ◽

Complex Molecules ◽

Form Complex ◽

Reaction Proceeds

Bicyclic aziridines undergo formal [3+3] ring expansion reactions when exposed to rhodium-bound vinyl carbenes to form complex dehydropiperidines in a highly stereocontrolled rearrangement. Mechanistic studies and DFT computations indicate the reaction proceeds through the formation of a vinyl aziridinium ylide; this reactive intermediate undergoes a concerted, asynchronous, pseudo-[1,4]- sigmatropic rearrangement to directly furnish the heterocyclic products with net retention at the new C-C bond. In combination with an asymmetric silver-catalyzed aziridination developed in our group, this method quickly delivers enantioenriched scaffolds with up to three contiguous stereocenters. The mild reaction conditions, functional group tolerance, and high stereochemical retention of this method are especially well-suited for appending piperidine motifs to natural product and complex molecules. Ultimately, our work establishes the value of underutilized aziridinium ylides as key intermediates in strategies to convert small, strained rings to larger N-heterocycles.

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