Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expanding Access to Remdesivir via an Improved Pyrrolotriazine Synthesis: Supply Centered Synthesis.

ABSTRACT: Pyrrolotriazine 1 is an important precursor to remdesivir. Initial results toward an efficient synthesis are disclosed consisting of sequential cyanation, amination, and triazine formation beginning from pyrrole. This route makes use of highly abundant, commoditized raw material inputs. The yield of triazine was doubled from 31% to 59%, and the synthetic step count was reduced from 4 to 2. These efforts help to secure the remdesivir supply chain.

SUBMITTER: Paymode DJ

PROVIDER: S-EPMC7536717 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Expanding Access to Remdesivir via an Improved Pyrrolotriazine Synthesis: Supply Centered Synthesis.

Paymode Dinesh J DJ Cardoso Flavio S P FSP Agrawal Toolika T Tomlin John W JW Cook Daniel W DW Burns Justina M JM Stringham Rodger W RW Sieber Joshua D JD Gupton B Frank BF Snead David R DR

Organic letters 20200915 19

Pyrrolotriazine <b>1</b> is an important precursor to remdesivir. Initial results toward an efficient synthesis are disclosed consisting of sequential cyanation, amination, and triazine formation beginning from pyrrole. This route makes use of highly abundant, commoditized raw material inputs. The yield of triazine was doubled from 31% to 59%, and the synthetic step count was reduced from 4 to 2. These efforts help to secure the remdesivir supply chain. ...[more]

PMID: 32931286

Similar Datasets

Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis.

Project description:A scalable four-step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile, and acetone. Isolation and purification procedures are improved in comparison to our earlier study as all intermediates can be isolated via recrystallization. The key steps in the synthesis, namely, ester formation, hydroxyamination, and deprotection were carried out on a multigram scale to afford molnupiravir in 36-41% yield with an average purity of 98 wt % by qNMR and 99 area% by HPLC.

| S-EPMC8689649 | biostudies-literature

Total synthesis of remdesivir.

Project description:Remdesivir, the first drug approved by the FDA to treat COVID-19, is in high demand for patients infected with the SARS-CoV-2 virus. Herein, we report a facile approach minimizing the protecting group manipulations to afford remdesivir in good overall yield.

| S-EPMC8656175 | biostudies-literature

An improved synthesis of pentacene: rapid access to a benchmark organic semiconductor.

Project description:Pentacene is an organic semiconductor used in a variety of thin-film organic electronic devices. Although at least six separate syntheses of pentacene are known (two from dihydropentacenes, two from 6,13-pentacenedione and two from 6,13-dihydro-6,13-dihydroxypentacene), none is ideal and several utilize elevated temperatures that may facilitate the oxidation of pentacene as it is produced. Here, we present a fast (-2 min of reaction time), simple, high-yielding (≥ 90%), low temperature synthesis of pentacene from readily available 6,13-dihydro-6,13-dihydroxypentacene. Further, we discuss the mechanism of this highly efficient reaction. With this improved synthesis, researchers gain rapid, affordable access to high purity pentacene in excellent yield and without the need for a time consuming sublimation.

| S-EPMC6268729 | biostudies-literature

Expanding the MicroRNA Targeting Code: A Novel Type of Site with Centered Pairing

Project description:We present “centered sites,” a class of microRNA target sites that lacks both perfect seed pairing and 3'-compensatory pairing and instead has 11–12 contiguous Watson–Crick pairs to the center of the microRNA. In elevated Mg2+, centered sites impart mRNA cleavage, but in cells, centered sites repress protein output without consequential Agronaute-catalyzed cleavage. Our study also identified novel extensively paired sites that are cleavage substrates in cultured cells and human brain. This expanded repertoire of cleavage targets and the identification of the centered site type help explain why central regions of many microRNAs are evolutionarily conserved. To study centered sites and identify miRNA cleavage targets, mRNA degradomes were sequenced from human brain and HeLa cells, and smallRNAs were sequenced from human brain and zebrafish embryo at 24 hours post fertilization (hpf). Replicates were combined before the analysis. Fastq files are not available for GSM548638 and GSM548639.

2010-06-25 | E-GEOD-22068 | biostudies-arrayexpress

Expanding the MicroRNA Targeting Code: A Novel Type of Site with Centered Pairing

2010-06-25 | GSE22068 | GEO

Expanding the microRNA targeting code: functional sites with centered pairing.

Project description:Most metazoan microRNA (miRNA) target sites have perfect pairing to the seed region, located near the miRNA 5' end. Although pairing to the 3' region sometimes supplements seed matches or compensates for mismatches, pairing to the central region has been known to function only at rare sites that impart Argonaute-catalyzed mRNA cleavage. Here, we present "centered sites," a class of miRNA target sites that lack both perfect seed pairing and 3'-compensatory pairing and instead have 11-12 contiguous Watson-Crick pairs to the center of the miRNA. Although centered sites can impart mRNA cleavage in vitro (in elevated Mg(2+)), in cells they repress protein output without consequential Argonaute-catalyzed cleavage. Our study also identified extensively paired sites that are cleavage substrates in cultured cells and human brain. This expanded repertoire of cleavage targets and the identification of the centered site type help explain why central regions of many miRNAs are evolutionarily conserved.

| S-EPMC2942757 | biostudies-literature

A Mild, Large-Scale Synthesis of 1,3-Cyclooctanedione: Expanding Access to Difluorinated Cyclooctyne for Copper-Free Click Chemistry.

Project description:We report the large-scale synthesis of 1,3-cyclooctanedione in five steps with 29% yield. This molecule is a synthetic precurser to difluorinated cyclooctyne, which participates in a bioorthogonal copper-free click reaction with azides. The final step demonstrates the first successful application of the Wacker-Tsuji oxidation to form a cyclic 1,3-dione.

| S-EPMC3103834 | biostudies-literature

Patient-Centered Access to IBD Care: A Qualitative Study.

Project description:BackgroundCanada has the highest global age-adjusted incidence and prevalence rates of inflammatory bowel disease (IBD). Due to IBD patient volumes and limited resources, challenges to timely access to specialty care have emerged. To address this gap, the aim of this paper was to understand the experiences and perspectives of persons living with IBD with a focus on accessing health care.MethodsUsing a qualitative descriptive approach, patients diagnosed with IBD (≥18 years of age) were purposively sampled from rural and urban gastroenterology clinics and communities across Canada. Co-facilitated by a researcher and patient research partner, 14 focus groups were recorded, transcribed, and coded for themes. Thematic analysis was used to ascertain the congruence or discordance of IBD specialty care access experiences.ResultsA total of 63 individuals participated in the study. The majority of participants were female (41/63, 65%) and from urban/suburban regions (33/63, 52%), with a mean age of 48.39 (range 16-77 years). The analysis generated three main themes: (1) need for patient to be partner, (2) adapting IBD care access to individual context, and (3) patient-defined care priorities should guide access to IBD care.ConclusionsThe complexity of specialty care access for IBD patients cannot be underestimated. It is vital to possess a robust understanding of healthcare system structures, processes, and the impact of these factors on accessing care. Using a patient-centered exploration of barriers and facilitators, IBD specialty care access in Canada can be better understood and improved on provincial and national levels.

| S-EPMC9825304 | biostudies-literature

User-centered design of central venous access device documentation.

Project description:ObjectiveSafe care of central venous access devices (CVAD) requires clinicians be able to identify key CVAD properties from insertion until safe removal. Our objective was to design and evaluate interfaces to improve CVAD documentation quality and information retrieval.Materials and methodsWe applied user-centered design (UCD) to CVAD property documentation interfaces. We measured expert agreement and front-line clinician accuracy in retrieving key properties in CVADs documented pre- and postimplementation.ResultsThe new approach (1) optimized searches for line types, (2) enabled discrete entry of key properties which propagated to the display name, and (3) facilitated error correction by experts. Expert agreement on key CVAD properties improved from 42% to 83% (P < 0.01). Frontline nurses' perception of key CVAD properties improved from 31% to 86% (P < 0.01). Ease of use scores improved from 15/100 to 80/100 (P < 0.01).ConclusionsUCD significantly improved data quality and nurse perception of CVAD properties to guide subsequent care.

| S-EPMC8903134 | biostudies-literature

Interprofessional advanced access - a quality improvement protocol for expanding access to primary care services.

Project description:BackgroundThe Advanced Access (AA) Model has shown considerable success in improving timely access for patients in primary care settings. As a result, a majority of family physicians have implemented AA in their organizations over the last decade. However, despite its widespread use, few professionals other than physicians and nurse practitioners have implemented the model. Among those who have integrated it to their practice, a wide variation in the level of implementation is observed, suggesting a need to support primary care teams in continuous improvement with AA implementation. This quality improvement research project aims to document and measure the processes and effects of practice facilitation, to implement and improve AA within interprofessional teams.MethodsFive primary care teams at various levels of organizational AA implementation will take part in a quality improvement process. These teams will be followed independently over PDSA (Plan-Do-Study-Act) cycles for 18 months. Each team is responsible for setting their own objectives for improvement with respect to AA. The evaluation process consists of a mixed-methods plan, including semi-structured interviews with key members of the clinical and management teams, patient experience survey and AA-related metrics monitored from Electronic Medical Records over time.DiscussionMost theories on organizational change indicate that practice facilitation should enable involvement of stakeholders in the process of change and enable improved interprofessional collaboration through a team-based approach. Improving access to primary care services is one of the top priorities of the Quebec's ministry of health and social services. This study will identify key barriers to quality improvement initiatives within primary care and help to develop successful strategies to help teams improve and broaden implementation of AA to other primary care professionals.

| S-EPMC8361639 | 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