scholarly journals Structures of low molecular weight inhibitors bound to MDMX and MDM2 reveal new approaches for p53-MDMX/MDM2 antagonist drug discovery

Cell Cycle ◽  
2010 ◽  
Vol 9 (6) ◽  
pp. 1104-1111 ◽  
Author(s):  
Grzegorz M. Popowicz ◽  
Anna Czarna ◽  
Siglinde Wolf ◽  
Kan Wang ◽  
Wei Wang ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Drug Discovery ◽  
Low Molecular Weight ◽  
Mdm2 Antagonist ◽  
New Approaches

scholarly journals Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors

2015 ◽  
Vol 94 ◽  
pp. 123-131 ◽  
Author(s):  
Brendan Frett ◽  
Nick McConnell ◽  
Catherine C. Smith ◽  
Yuanxiang Wang ◽  
Neil P. Shah ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Drug Discovery ◽  
Low Molecular Weight ◽  
Computer Aided ◽  
Flt3 Inhibitors

2-Aminopyridine - An unsung hero in drug discovery

2021 ◽  
Author(s):  
nishanth ramdas ◽  
Kaushik Chanda
Keyword(s):  
Molecular Weight ◽  
Drug Discovery ◽  
Biological Molecules ◽  
Low Molecular Weight

Abstract 2-aminopyridine is a simple, low molecular weight and perfectly functionalized moiety known for the synthesis of diverse biological molecules. Many pharma stations across the globe aim to synthesize and...

scholarly journals Investigating 3,3-Diaryloxetanes as Potential Bioisosteres in Drug Discovery

2021 ◽  
Author(s):  
Maryne A. J. Dubois ◽  
Rosemary Croft ◽  
Yujie Ding ◽  
Chulho Choi ◽  
Dafydd R. Owen ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Drug Discovery ◽  
Physicochemical Properties ◽  
Chemical Properties ◽  
Low Molecular Weight ◽  
Design Element ◽  
Carbonyl Groups ◽  
Design And Synthesis ◽  
Target Molecules ◽  
Pair Analysis

<div><div><div><p>Oxetanes have received increasing interest in medicinal chemistry as attractive polar and low molecular weight motifs. The application of oxetanes as replacements for methylene, methyl, gem-dimethyl and carbonyl groups has been demonstrated to often improve chemical properties of target molecules for drug discovery purposes. The investigation of the properties of 3,3-diaryloxetanes, particularly of interest as a benzophenone replacement, remains largely unexplored. With recent synthetic advances in accessing this motif we studied the effects of 3,3-diaryloxetanes on the physicochemical properties of ‘drug-like’ molecules. Here, we describe our efforts in the design and synthesis of a range of drug-like compounds for matched molecular pair analysis to investigate the viability of the 3,3-diaryloxetane motif as a replacement group in drug discovery. We conclude that the properties of the diaryloxetanes and ketones are similar, and generally superior to related alkyl linkers, and that diaryloxetanes provide a potentially useful new design element.</p></div></div></div>

scholarly journals Investigating 3,3-Diaryloxetanes as Potential Bioisosteres in Drug Discovery

2021 ◽  
Author(s):  
Maryne A. J. Dubois ◽  
Rosemary Croft ◽  
Yujie Ding ◽  
Chulho Choi ◽  
Dafydd R. Owen ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Drug Discovery ◽  
Physicochemical Properties ◽  
Chemical Properties ◽  
Low Molecular Weight ◽  
Design Element ◽  
Carbonyl Groups ◽  
Design And Synthesis ◽  
Target Molecules ◽  
Pair Analysis

<div><div><div><p>Oxetanes have received increasing interest in medicinal chemistry as attractive polar and low molecular weight motifs. The application of oxetanes as replacements for methylene, methyl, gem-dimethyl and carbonyl groups has been demonstrated to often improve chemical properties of target molecules for drug discovery purposes. The investigation of the properties of 3,3-diaryloxetanes, particularly of interest as a benzophenone replacement, remains largely unexplored. With recent synthetic advances in accessing this motif we studied the effects of 3,3-diaryloxetanes on the physicochemical properties of ‘drug-like’ molecules. Here, we describe our efforts in the design and synthesis of a range of drug-like compounds for matched molecular pair analysis to investigate the viability of the 3,3-diaryloxetane motif as a replacement group in drug discovery. We conclude that the properties of the diaryloxetanes and ketones are similar, and generally superior to related alkyl linkers, and that diaryloxetanes provide a potentially useful new design element.</p></div></div></div>

Fragment-based drug discovery and its application to challenging drug targets

2017 ◽  
Vol 61 (5) ◽  
pp. 475-484 ◽  
Author(s):  
Amanda J. Price ◽  
Steven Howard ◽  
Benjamin D. Cons
Keyword(s):  
Molecular Weight ◽  
Drug Discovery ◽  
Drug Targets ◽  
Structural Information ◽  
New Drugs ◽  
Low Molecular Weight ◽  
Related Factor ◽  
X Ray ◽  
X Ray Crystallography ◽  
Fragment Based Drug Discovery

Fragment-based drug discovery (FBDD) is a technique for identifying low molecular weight chemical starting points for drug discovery. Since its inception 20 years ago, FBDD has grown in popularity to the point where it is now an established technique in industry and academia. The approach involves the biophysical screening of proteins against collections of low molecular weight compounds (fragments). Although fragments bind to proteins with relatively low affinity, they form efficient, high quality binding interactions with the protein architecture as they have to overcome a significant entropy barrier to bind. Of the biophysical methods available for fragment screening, X-ray protein crystallography is one of the most sensitive and least prone to false positives. It also provides detailed structural information of the protein–fragment complex at the atomic level. Fragment-based screening using X-ray crystallography is therefore an efficient method for identifying binding hotspots on proteins, which can then be exploited by chemists and biologists for the discovery of new drugs. The use of FBDD is illustrated here with a recently published case study of a drug discovery programme targeting the challenging protein–protein interaction Kelch-like ECH-associated protein 1:nuclear factor erythroid 2-related factor 2.

A high-performance oil-free backing pump for electron microscopes

1978 ◽  
Vol 36 (1) ◽  
pp. 110-111
Author(s):  
G.K.W. Balkau ◽  
E. Bez ◽  
J.L. Farrant
Keyword(s):  
Molecular Weight ◽  
Electron Microscope ◽  
Hot Spots ◽  
High Performance ◽  
Carbonaceous Material ◽  
Contamination Rate ◽  
Low Molecular Weight ◽  
Principal Source ◽  
Rotary Pumps ◽  
Electron Microscopes

The earliest account of the contamination of electron microscope specimens by the deposition of carbonaceous material during electron irradiation was published in 1947 by Watson who was then working in Canada. It was soon established that this carbonaceous material is formed from organic vapours, and it is now recognized that the principal source is the oil-sealed rotary pumps which provide the backing vacuum. It has been shown that the organic vapours consist of low molecular weight fragments of oil molecules which have been degraded at hot spots produced by friction between the vanes and the surfaces on which they slide. As satisfactory oil-free pumps are unavailable, it is standard electron microscope practice to reduce the partial pressure of organic vapours in the microscope in the vicinity of the specimen by using liquid-nitrogen cooled anti-contamination devices. Traps of this type are sufficient to reduce the contamination rate to about 0.1 Å per min, which is tolerable for many investigations.

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