An Advance In Medicinal Chemistry

<p><br></p> <p>A method to activate sulfamoyl fluorides, fluorosulfates, and sulfonyl fluorides with calcium triflimide, and DABCO for SuFEx with amines is described. The reaction was applied to a diverse set of sulfamides, sulfamates, and sulfonamides at room temperature under mild conditions. Additionally, we highlight the application of this transformation to parallel medicinal chemistry to generate a broad array of nitrogen-based S(VI) compounds. </p>

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SuFEx Activation with Ca(NTf2)2: A Unified Strategy to Access Sulfamides, Sulfamates and Sulfonamides from S(VI) Fluorides

10.26434/chemrxiv.12026811 ◽

2020 ◽

Author(s):

Subham Mahapatra ◽

Cristian P. Woroch ◽

Todd W. Butler ◽

Sabrina N. Carneiro ◽

Sabrina C. Kwan ◽

...

Keyword(s):

Room Temperature ◽

Medicinal Chemistry ◽

Mild Conditions ◽

Broad Array

<p><br></p> <p>A method to activate sulfamoyl fluorides, fluorosulfates, and sulfonyl fluorides with calcium triflimide, and DABCO for SuFEx with amines is described. The reaction was applied to a diverse set of sulfamides, sulfamates, and sulfonamides at room temperature under mild conditions. Additionally, we highlight the application of this transformation to parallel medicinal chemistry to generate a broad array of nitrogen-based S(VI) compounds. </p>

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Cascade CuH-Catalyzed Conversion of Alkynes to Enantioenriched 1,1-Disubstituted Products

10.26434/chemrxiv.7961633.v1 ◽

2019 ◽

Author(s):

De-Wei Gao ◽

Yang Gao ◽

Huiling Shao ◽

Tian-Zhang Qiao ◽

Xin Wang ◽

...

Keyword(s):

Organic Synthesis ◽

Medicinal Chemistry ◽

Proteasome Inhibitors ◽

Building Blocks ◽

Unique Role ◽

Efficient Strategy ◽

Carbon Centers ◽

Rapid Access ◽

Cascade Catalysis ◽

Privileged Scaffolds

Enantioenriched <i>α</i>-aminoboronic acids play a unique role in medicinal chemistry and have emerged as privileged pharmacophores in proteasome inhibitors. Additionally, they represent synthetically useful chiral building blocks in organic synthesis. Recently, CuH-catalyzed asymmetric alkene hydrofunctionalization has become a powerful tool to construct stereogenic carbon centers. In contrast, applying CuH cascade catalysis to achieve reductive 1,1-difunctionalization of alkynes remains an important, but largely unaddressed, synthetic challenge. Herein, we report an efficient strategy to synthesize <i>α</i>-aminoboronates <i>via </i>CuH-catalyzed hydroboration/hydroamination cascade of readily available alkynes. Notably, this transformation selectively delivers the desired 1,1-heterodifunctionalized product in favor of alternative homodifunctionalized, 1,2-heterodifunctionalized, or reductively monofunctionalized byproducts, thereby offering rapid access to these privileged scaffolds with high chemo-, regio- and enantioselectivity.<br>

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Medicinal Chemistry Database GDBMedChem

10.26434/chemrxiv.7770809.v1 ◽

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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