scholarly journals Difluorination of α-(Bromomethyl)styrenes via I(I)/I(III) Catalysis: Facile Access to Electrophilic Linchpins for Drug Discovery

2021 ◽  
Author(s):  
Joel Häfliger ◽  
Keith Livingstone ◽  
Constantin Daniliuc ◽  
Ryan Gilmour
Keyword(s):  
Drug Discovery ◽  
Building Blocks ◽  
Main Group

Simple α-(bromomethyl)styrenes can be processed to a variety of 1,1-difluorinated electrophilic building blocks via I(I)/I(III) catalysis. This inexpensive main group catalysis strategy employs p-TolI as an effective organocatalyst when combined...

Synthesis of sp3-Enriched β-Fluoro Sulfonyl Chlorides

Synthesis ◽  
2020 ◽  
Author(s):  
Oleksandr O. Grygorenko ◽  
Rustam Gurbanov ◽  
Andriy Sokolov ◽  
Sergey Golovach ◽  
Kostiantyn Melnykov ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Double Bond ◽  
Building Blocks ◽  
Protecting Groups ◽  
Sulfonyl Chlorides ◽  
Wide Range ◽  
Cyclic Compounds

AbstractA three-step approach to the synthesis of sp3-enriched β-fluoro sulfonyl chlorides starting from alkenes is reported. The method was successfully applied to a wide range of acyclic and cyclic substrates, bearing either an exocyclic or an endocyclic double bond. The procedure worked with a wide range of substrates and tolerated a number of functional and protecting groups. Moreover, the target cyclic compounds were obtained as single cis diastereomers on a multigram scale. The title compounds are promising building blocks for drug discovery that can be used to obtain sp3-enriched β-fluoro and α,β-unsaturated sulfonamides.

Neue Cyclophosphazene mit Metallen der III. Hauptgruppe als Ringbausteine / New Cyclophosphazenes with Metals of Main Group III as Building Blocks

1994 ◽  
Vol 49 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Reinhard Hasselbring ◽  
Herbert W. Roesky ◽  
Andreas Heine ◽  
Dietmar Stalke ◽  
George M. Sheldrick
Keyword(s):  
Nmr Spectroscopy ◽  
Structure Determination ◽  
Building Blocks ◽  
Main Group ◽  
Ring Formation ◽  
Lewis Acidity ◽  
X Ray ◽  
Group Iii ◽  
Space Groups ◽  
Ring Compounds

Abstract Acylic silylated phosphazenes of the type HN(PR2NSiMe3)2 (1) react quantitatively with molecules MMe3 (M = Al, Ga, In) under ring formation and CH4 evolution. The ring compounds N(PPh2NSiMe3)2AlMe2 (2 a) and N(PPh2NSiMe3)2InMe2 (4 a) have been investiga­ ted by X-ray structure determination. 2a and 4a crystallize in the space groups P 1̄ and P 31, respectively; they show different conformations regarding the cyclohexane framework. NMR spectroscopy of the nuclei in the chelating phosphazene ligand indicates decreasing Lewis acidity of the metal containing fragments in the series AlMe2 ≥ GaMe2 > InMe2.

scholarly journals Synthetically Accessible Virtual Inventory (SAVI)

2020 ◽  
Author(s):  
Hitesh Patel ◽  
Wolf Ihlenfeldt ◽  
Philip Judson ◽  
Yurii S. Moroz ◽  
Yuri Pevzner ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Chemical Synthesis ◽  
Programming Languages ◽  
Expert Knowledge ◽  
Scoring Systems ◽  
Building Blocks ◽  
Single Step

We have made available a database of over 1 billion compounds predicted to be easily synthesizable. They have been created by a set of transforms based on an adaptation and extension of the CHMTRN/PATRAN programming languages describing chemical synthesis expert knowledge, which originally stem from the LHASA project. The chemoinformatics toolkit CACTVS was used to apply a total of 53 transforms to about 150,000 readily available building blocks (enamine.net). Only single-step, two-reactant syntheses were calculated for this database even though the technology can execute multi-step reactions. The possibility to incorporate scoring systems in CHMTRN allowed us to subdivide the database of 1.75 billion compounds in sets according to their predicted synthesizability, with the most-synthesizable class comprising 1.09 billion synthetic products. Properties calculated for all SAVI products show that the database should be well-suited for drug discovery. It is being made publicly available for free download from https://cactus.nci.nih.gov/download/savi_download/.

scholarly journals Cover Feature: Synthesis of Functionalized Difluorocyclopropanes: Unique Building Blocks for Drug Discovery (Chem. Eur. J. 47/2018)

2018 ◽  
Vol 24 (47) ◽  
pp. 12102-12102
Author(s):  
Roman M. Bychek ◽  
Vadym V. Levterov ◽  
Iryna V. Sadkova ◽  
Andrey A. Tolmachev ◽  
Pavel K. Mykhailiuk
Keyword(s):  
Drug Discovery ◽  
Building Blocks

Glycosylated α-Azido Amino Acids: Versatile Intermediates in the Synthesis of Neoglycoconjugates

Synlett ◽  
2018 ◽  
Vol 29 (07) ◽  
pp. 904-907 ◽  
Author(s):  
Trinidad Velasco-Torrijos ◽  
Róisín O’Flaherty
Keyword(s):  
Amino Acids ◽  
Drug Discovery ◽  
Building Blocks ◽  
Sensor Development ◽  
Galactosyl Ceramide

A series of glycosylated α-azido amino acids was synthesized as precursors for neoglycoconjugates, a class of important biomolecules for drug discovery, and sensor development. The synthetically challenging 1,2-cis α-galactosylated species described herein were designed as building blocks in the synthesis of analogues of α-galactosyl ceramide, a potent immunomodulator. A benzyl-protected 1,2,3-triazolyl α-galactosyl-l-serine derivative was prepared using copper azide alkyne cycloaddition to showcase the potential of glycosylated α-azido amino acids in neoglycoconjugate design.

Diastereoselective Synthesis of 2-Phenyl-3-(trifluoromethyl)piperazines as Building Blocks for Drug Discovery

2014 ◽  
Vol 79 (12) ◽  
pp. 5887-5894 ◽  
Author(s):  
María Sánchez-Roselló ◽  
Oscar Delgado ◽  
Natalia Mateu ◽  
Andrés A. Trabanco ◽  
Michiel Van Gool ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Building Blocks ◽  
Diastereoselective Synthesis

scholarly journals The Generated Databases (GDBs) as a Source of 3D-shaped Building Blocks for Use in Medicinal Chemistry and Drug Discovery

2020 ◽  
Vol 74 (4) ◽  
pp. 241-246 ◽  
Author(s):  
Kris Meier ◽  
Sven Bühlmann ◽  
Josep Arús-Pous ◽  
Jean-Louis Reymond
Keyword(s):  
Drug Discovery ◽  
Medicinal Chemistry ◽  
Organic Molecules ◽  
Chemical Space ◽  
Building Blocks ◽  
Chiral Molecules ◽  
Hydrogen Atoms ◽  
Quaternary Centers ◽  
Medical Needs ◽  
Unmet Medical Needs

Drug discovery is in constant need of new molecules to develop drugs addressing unmet medical needs. To assess the chemical space available for drug design, our group investigates the generated databases (GDBs) listing all possible organic molecules up to a defined size, the largest of which is GDB-17 featuring 166.4 billion molecules up to 17 non-hydrogen atoms. While known drugs and bioactive compounds are mostly aromatic and planar, the GDBs contain a plethora of non-aromatic 3D-shaped molecules, which are very useful for drug discovery since they generally have more desirable absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. Here we review GDB enumeration methods and the selection and synthesis of GDB molecules as modulators of ion channels. We summarize the constitution of GDB subsets focusing on fragments (FDB17), medicinal chemistry (GDBMedChem) and ChEMBL-like molecules (GDBChEMBL), and the ring system database GDB4c as a rich source of novel 3D-shaped chiral molecules containing quaternary centers, such as the recently reported trinorbornane.

scholarly journals An Approach to 1,1-Disubstituted Pyrazolylcyclopropane Building Blocks

SynOpen ◽  
2017 ◽  
Vol 01 (01) ◽  
pp. 0084-0090 ◽  
Author(s):  
Pavel Nosik ◽  
Oleksiy Artamonov ◽  
Sergey Ryabukhin ◽  
Oleksandr Grygorenko
Keyword(s):  
Drug Discovery ◽  
Building Blocks ◽  
Lithium Diisopropylamide ◽  
Early Drug

An approach to isomeric 1,1-disubstituted pyrazolylcyclopropanes that relies on lithium diisopropylamide (LDA) mediated bis-alkylation­ of the corresponding pyrazolylacetonitriles is developed. The building blocks obtained can be considered as lead-like bioisosteres of arylpyrazole and pyrazolecarboxamide moieties and are thus useful for early drug discovery projects.

scholarly journals Synthesis of Spirocyclic Pyrrolidines: Advanced Building Blocks for Drug Discovery

2017 ◽  
Vol 23 (66) ◽  
pp. 16695-16695 ◽  
Author(s):  
Bohdan A. Chalyk ◽  
Maryna V. Butko ◽  
Oksana O. Yanshyna ◽  
Konstantin S. Gavrilenko ◽  
Tetiana V. Druzhenko ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Building Blocks
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