Emerging building blocks for medicinal chemistry: recent synthetic advances

2021 ◽  
Author(s):  
Oleksandr O Grygorenko ◽  
Dmitriy M. Volochnyuk ◽  
Bohdan V. Vashchenko
Keyword(s):  
Medicinal Chemistry ◽  
Building Blocks

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

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>

scholarly journals Janus All‐Cis 2,3,4,5,6‐Pentafluorocyclohexyl Building Blocks Applied to Medicinal Chemistry and Bioactives Discovery Chemistry

2021 ◽  
Author(s):  
Joshua L. Clark ◽  
Rifahath M. Neyyappadath ◽  
Cihang Yu ◽  
Alexandra M. Z. Slawin ◽  
David B. Cordes ◽  
...  
Keyword(s):  
Medicinal Chemistry ◽  
Building Blocks

scholarly journals Chromene- and Quinoline-3-Carbaldehydes: Useful Intermediates in the Synthesis of Heterocyclic Scaffolds

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3791
Author(s):  
Djenisa H. A. Rocha ◽  
Vasco F. Batista ◽  
Emanuel J. F. Balsa ◽  
Diana C. G. A. Pinto ◽  
Artur M. S. Silva
Keyword(s):  
Medicinal Chemistry ◽  
Building Blocks

Chromenes and quinolines are recognized as important scaffolds in medicinal chemistry. Herein, the efficient use of chromene- and quinoline-3-carbaldehydes to synthesize other valuable heterocycles is described. These carbaldehydes are obtained in excellent yields through the Vilsmeyer-Haack reaction of flavanones and azaflavanones. Protocols towards the synthesis of new heterocycles, such as 3H-chromeno[3–c]quinolines, (Z/E)-2-aryl-4-chloro-3-styryl-2H-chromenes, and (E)-2-aryl-4-chloro-3-styrylquinoline-1(2H)-carbaldehydes were established. Altogether, we demonstrate the value of chromene- and quinoline-3-carbaldehydes as building blocks.

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.

A New Synthesis of 4,5,6,7-Tetrahydropyrazolo[1,5-c]pyrimidines by a Retro-Mannich Cascade Rearrangement

2014 ◽  
Vol 67 (3) ◽  
pp. 420 ◽  
Author(s):  
Raffaele Colombo ◽  
Kyu Ok Jeon ◽  
Donna M. Huryn ◽  
Matthew G. LaPorte ◽  
Peter Wipf
Keyword(s):  
Mannich Reaction ◽  
Medicinal Chemistry ◽  
Hydrolysis Product ◽  
Building Blocks ◽  
Biological Applications ◽  
Heterocyclic Chemistry ◽  
New Synthesis ◽  
Rearrangement Process

We discovered a new retro-Mannich reaction of in situ prepared pyrazolopyridines to give pyrazolopyrimidines that have hitherto been underrepresented in the heterocyclic chemistry literature. The isolation of a linear hydrolysis product supports a mechanistic hypothesis for this rearrangement process. In order to establish a broader access and explore potential biological applications for these medicinal chemistry building blocks, we investigated the scope of the reaction and generated small amine- as well as amide-based libraries through reductive aminations and amide couplings, respectively.

ChemInform Abstract: Cubanes in Medicinal Chemistry: Synthesis of Functionalized Building Blocks.

ChemInform ◽  
2014 ◽  
Vol 45 (51) ◽  
pp. no-no
Author(s):  
Joanna Wlochal ◽  
Robert D. M. Davies ◽  
Jonathan Burton
Keyword(s):  
Medicinal Chemistry ◽  
Building Blocks

scholarly journals Bridged Bicyclic Building Block Upgrading: Photochemical Synthesis of bicyclo[3.1.1]heptan-1-Amines

2020 ◽  
Author(s):  
Alexander Harmata ◽  
Madison Sowden ◽  
Corey Stephenson
Keyword(s):  
Building Block ◽  
Primary Amine ◽  
Medicinal Chemistry ◽  
Building Blocks ◽  
Photochemical Synthesis ◽  
Wide Range ◽  
Hydrolysis Of

Compounds containing bridged bicyclic carbon skeletons are desirable building blocks for medicinal chemistry. However, as a result of their inefficient, linear syntheses, commercially available compounds of this sort are plagued by high costs and/or a lack of diversity in substitution patterns. Herein we report the conversion of the readily available bicyclo[1.1.1]pentan-1-amine substructure to a wide range of poly-substituted bicyclo[3.1.1]pentan-1-amines using imine photochemistry. To our knowledge, this is the first reported method to convert the bicyclo[1.1.1]pentane skeleton to the bicyclo[3.1.1]heptane skeleton. Hydrolysis of the imine products gives complex, sp<sup>3</sup>-rich primary amine building blocks.

scholarly journals Quick Building Blocks (QBB): An Innovative and Efficient Business Model To Speed Medicinal Chemistry Analog Synthesis

2019 ◽  
Vol 10 (8) ◽  
pp. 1104-1109 ◽  
Author(s):  
Christopher J. Helal ◽  
Mark Bundesmann ◽  
Susan Hammond ◽  
Melissa Holmstrom ◽  
Jacquelyn Klug-McLeod ◽  
...  
Keyword(s):  
Business Model ◽  
Medicinal Chemistry ◽  
Building Blocks ◽  
Analog Synthesis

scholarly journals Iridium-catalysed C–H borylation of β-aryl-aminopropionic acids

2020 ◽  
Vol 18 (34) ◽  
pp. 6696-6701
Author(s):  
Henry Robinson ◽  
Joe Stillibrand ◽  
Klemensas Simelis ◽  
Simon J. F. Macdonald ◽  
Andrew Nortcliffe
Keyword(s):  
Medicinal Chemistry ◽  
Building Blocks ◽  
One Pot

Iridium-catalysed C–H borylation of β-aryl-aminopropionic acid derivatives gives 3,5-functionalised protected β-aryl-aminopropionic acid boronates. One-pot borylation–functionalisation provides diverse building blocks for medicinal chemistry.

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