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 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

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.

scholarly journals Critical Minireview: The Fate of tRNACys during Oxidative Stress in Bacillus subtilis

2016 ◽  
Author(s):  
Juan Campos Guillen ◽  
George H. Jones ◽  
Carlos Saldaña Gutierrez ◽  
José Luis Hernández Flores ◽  
Julio Alfonso Cruz Medina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Weight ◽  
Bacillus Subtilis ◽  
Essential Gene ◽  
Biological Molecules ◽  
Low Molecular Weight ◽  
Oxygen Species ◽  
Bacterial Response ◽  
Protein Thiols ◽  
And Oxidative Stress

Oxidative stress occurs when cells are exposed to elevated levels of reactive oxygen species that could damage biological molecules. One bacterial response to oxidative stress involves disulfide bond formation either between protein thiols or between protein thiols and low-molecular-weight thiols. Bacillithiol was recently identified as a major low-molecular-weight thiol in Bacillus subtilis and related Firmicutes. Four genes (bshA, bshB1, bshB2 and bshC) are involved in bacillithiol biosynthesis. The bshA and bshB1 genes are part of a seven-gene operon (ypjD), which includes the essential gene cca, encoding CCA-tRNA nucleotidyltransferase. The inclusion of cca in the operon containing bacillithiol biosynthetic genes suggests that the integrity of the 3&rsquo; terminus of tRNAs may also be important in oxidative stress. Addition of the 3&acute; terminal CCA sequence by CCA-tRNA nucleotidyltransferase to give a mature tRNA and functional molecules ready for aminoacylation plays an essential role during translation and expression of the genetic code. Any defects in these processes, for example, the accumulation of shorter and defective tRNAs under oxidative stress, could exert a deleterious effect on cells. This review summarizes the physiological link between tRNACys regulation and oxidative stress in Bacillus.

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
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