Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expanding the Repertoire of Low-Molecular-Weight Pentafluorosulfanyl-Substituted Scaffolds.

ABSTRACT: The pentafluorosulfanyl (-SF₅ ) functional group is of increasing interest as a bioisostere in medicinal chemistry. A library of SF₅ -containing compounds, including amide, isoxazole, and oxindole derivatives, was synthesised using a range of solution-based and solventless methods, including microwave and ball-mill techniques. The library was tested against targets including human dihydroorotate dehydrogenase (HDHODH). A subsequent focused approach led to synthesis of analogues of the clinically used disease modifying anti-rheumatic drugs (DMARDs), Teriflunomide and Leflunomide, considered for potential COVID-19 use, where SF₅ bioisostere deployment led to improved inhibition of HDHODH compared with the parent drugs. The results demonstrate the utility of the SF₅ group in medicinal chemistry.

SUBMITTER: Jose A

PROVIDER: S-EPMC9305131 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Preparation and Evaluation of Potent Pentafluorosulfanyl-Substituted Anti-Tuberculosis Compounds.

Project description:The global fight to stop tuberculosis (TB) remains a great challenge, particularly with the increase in drug-resistant strains and a lack of funding to support the development of new treatments. To bolster a precarious drug pipeline, we prepared a focused panel of eight pentafluorosulfanyl (SF5 ) compounds which were screened for their activity against Mycobacterium tuberculosis (Mtb) H37Rv in three different assay conditions and media. All eight compounds had sub-micromolar potency, and four displayed MICs <100?nm. Seven compounds were evaluated against non-replicating and mono-drug-resistant Mtb, and for their ability to inhibit Mtb within the macrophage. The greatest potency was observed against intracellular Mtb (MIC <10?nm for three compounds), which is often the most challenging to target. In general, the SF5 -bearing compounds were very similar to their CF3 counterparts, with the major differences observed being their in?vitro ADME properties. Two SF5 -bearing compounds were found to have greater protein binding than their corresponding CF3 counterparts, but were also less metabolized in human microsomes, resulting in longer half-lives.

| S-EPMC5603227 | biostudies-literature

Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes.

Project description:Oxidation of 3- and 4-pentafluorosulfanyl-substituted anisoles and phenols with hydrogen peroxide and sulfuric acid provided a mixture of SF5-substituted muconolactone, maleic, and succinic acids. A plausible mechanism for the formation of the aliphatic SF5 compounds was presented and their chemical reactivity was investigated. SF5-substituted para-benzoquinone was synthesized; its oxidation led to an improved yield of 2-(pentafluorosulfanyl)maleic acid. The reaction of SF5-substituted maleic anhydride and para-benzoquinone with cyclopentadiene afforded the Diels-Alder adducts. Decomposition of 3-(pentafluorosulfanyl)muconolactone in acidic, neutral and basic aqueous media was investigated and the decarboxylation of 2-(pentafluorosulfanyl)maleic acid provided 3-(pentafluorosulfanyl)acrylic acid.

| S-EPMC4734437 | biostudies-literature

Expanding the repertoire of natural product-inspired ring pairs for molecular recognition of DNA.

Project description:A furan amino acid, inspired by the recently discovered proximicin natural products, was incorporated into the scaffold of a DNA-binding hairpin polyamide. While unpaired oligomers of 2,4-disubstituted furan amino acids show poor DNA-binding activity, furan (Fn) carboxamides paired with N-methylpyrrole (Py) and N-methylimidazole (Im) rings demonstrate excellent stabilization of duplex DNA as well as discrimination of noncognate sequences, consistent with function as a Py mimic according to the Py/Im polyamide pairing rules.

| S-EPMC3195311 | biostudies-other

Expanding the molecular recognition repertoire of antifreeze polypeptides: effects on nucleoside crystal growth.

Project description:Despite differences in the crystal structures of ice and nucleosides, antifreeze polypeptides (AFPs) have been demonstrated to inhibit nucleation of 5-methyluridine, cytidine, and inosine and modify the crystal growth of the nucleosides efficiently. The molecular recognition repertoire of AFPs has been expanded to non-ice-like crystalline solids.

| S-EPMC3501450 | biostudies-literature

The Low Molecular Weight Proteome of Halobacterium salinarum

Project description:LMW Protein enrichment via cutt-off membrane filtration and unstained GeLC-MS/MS

2011-07-13 | PRD000430 | Pride

Molecular markers of predictive value associated with low birth weight

Project description:Sub-optimal fetal development is associated with an increased risk of developing cardiovascular disease, type 2 diabetes (T2D) and adiposity later in life. However, definitions of intrauterine growth restriction (IUGR) and small for gestational age (SGA) are based on simple statistical approaches that may misclassify infants with a normal developmental profile and vice versa. We used an unbiased global profiling approach to identify gene expression patterns in umbilical cord tissue from 38 infants and identified a set of 466 genes which separated the subjects into 2 distinct groups – one biased towards lower birth weight and one biased towards normal birth weight. The data suggest that approximately 30% of children of normal size have a molecular profile more typical of impaired fetal development and who may be on a programmed trajectory. Differences in expression between the two groups encompassed 384 upregulated and 82 downregulated genes. Molecular profiling at birth may have utility in identifying markers that potentially reflect antenatal developmental and may be predictive of future phenotypic development after birth. Importantly, it may provide an alternative to the current classification of infants using birth weights.

2011-10-21 | GSE24818 | GEO

Molecular markers of predictive value associated with low birth weight

2011-10-20 | E-GEOD-24818 | biostudies-arrayexpress

Low Molecular Weight Allergens from English Walnut (Juglans Regia)

Project description:Low molecular weight (LMW) proteins were purified from English walnuts (J. regia cv. Chandler). The LMW proteins were separated by anion exchange chromatography. The anion exchange fractions were analyzed by SDS-PAGE, and protein bands were excised. In gel trypsin digestion was conducted (following reduction with DTT and alkylation with iodoacetamide). Peptides were separated by RP-HPLC and analyzed with an LTQ Orbitrap XL. Peptide and protein identifications were obtained with Mascot.

2019-11-28 | PXD000634 | Pride

Expanding Repertoire of Plant Positive-Strand RNA Virus Proteases.

Project description:Many plant viruses express their proteins through a polyprotein strategy, requiring the acquisition of protease domains to regulate the release of functional mature proteins and/or intermediate polyproteins. Positive-strand RNA viruses constitute the vast majority of plant viruses and they are diverse in their genomic organization and protein expression strategies. Until recently, proteases encoded by positive-strand RNA viruses were described as belonging to two categories: (1) chymotrypsin-like cysteine and serine proteases and (2) papain-like cysteine protease. However, the functional characterization of plant virus cysteine and serine proteases has highlighted their diversity in terms of biological activities, cleavage site specificities, regulatory mechanisms, and three-dimensional structures. The recent discovery of a plant picorna-like virus glutamic protease with possible structural similarities with fungal and bacterial glutamic proteases also revealed new unexpected sources of protease domains. We discuss the variety of plant positive-strand RNA virus protease domains. We also highlight possible evolution scenarios of these viral proteases, including evidence for the exchange of protease domains amongst unrelated viruses.

| S-EPMC6357015 | biostudies-literature

Stereoselective, Multicomponent Approach to Quaternary Substituted Hydroindole Scaffolds.

Project description:The Amaryllidaceae alkaloids have been a target of synthesis for decades due to their complex architectures and biological activity. A central feature of these natural product cores is a quaternary substituted hydroindole heterocycle. Building off the foundation of our previous multicomponent approach to highly functionalized pyrrolidinones, herein we report a highly convergent, diastereoselective, multicomponent approach to access the hydroindole cores present within crinine, haemanthamine, pretazettine, and various other bioactive alkaloids. These scaffolds are additionally useful as building blocks for druglike molecules and natural product like library generation.

| S-EPMC7662074 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data