About: Synthesis and pre-clinical studies of new amino-acid ester thiazolide prodrugs

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Synthesis and pre-clinical studies of new amino-acid ester thiazolide prodrugs Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Synthesis and pre-clinical studies of new amino-acid ester thiazolide prodrugs
Creator	Cooper, Mark Norton, Daniel Reynolds, Stephen Rossignol, Jean-François Swift, Karl Slonecker, Steven Stachulski, Andrew
Source	Elsevier; Medline; PMC
abstract	Abstract Thiazolides are polypharmacology agents with at least three mechanisms of action against a broad spectrum of parasites, bacteria and viruses. In respiratory viruses they inhibit the replication of orthomyxoviridae and paramyxoviridae at a post-translational level. Nitazoxanide 1a, the prototype thiazolide, was originally developed as an antiparasitic agent and later repurposed for the treatment of viral respiratory infections. The second generation thiazolides following nitazoxanide, such as the 5-chloro analogue RM-5038 2a, are also broad-spectrum antiviral agents as we have reported. Both 1a and its effective circulating metabolite, tizoxanide 1b, are 5-nitrothiazole derivatives, while RM-5038 2a and its de-acetyl derivative RM-4848 2b are the corresponding 5-chloro derivatives. Recently 1a has completed phase II-III clinical trials in the United States, Canada, Australia and New Zealand in a total of 2865 adults and adolescents of at least 12 months of age with viral acute respiratory illness. Since its biodisposition is primarily seen in the gastro-intestinal tract, its efficacy in systemic viral diseases requires relatively high oral doses. The chemical synthesis of new derivatives with a better systemic absorption was therefore urgently needed. In order to improve their systemic absorption, new amino-ester prodrug derivatives of 1b and RM4848 2b were prepared and tested for their animal pharmacology, pharmacokinetics and toxicology. RM-5061 8a in rats showed 7-fold higher blood concentration compared to 1a: absolute bioavailability increased from 3 to 20%, with a good safety profile in animal safety pharmacology and toxicology.
has issue date	2017-01-27(xsd:dateTime)
bibo:doi	10.1016/j.ejmech.2016.09.080
bibo:pmid	27750149
has license	els-covid
sha1sum (hex)	bcf83e40d1a31377cd8c4a2849130aeb78da1991
schema:url	https://doi.org/10.1016/j.ejmech.2016.09.080
resource representing a document's title	Synthesis and pre-clinical studies of new amino-acid ester thiazolide prodrugs
has PubMed Central identifier	PMC7125651
has PubMed identifier	27750149
schema:publication	European Journal of Medicinal Chemistry
resource representing a document's body	covid:bcf83e40d1a31377cd8c4a2849130aeb78da1991#body_text
is schema:about of	named entity 'CLINICAL STUDIES' named entity 'action' named entity 'prodrug' named entity 'New Zealand' named entity 'viral' named entity 'Both' named entity 'prototype' named entity 'good' named entity 'prodrugs' named entity 'SYNTHESIS' covid:arg/bcf83e40d1a31377cd8c4a2849130aeb78da1991 named entity 'CHEMICAL SYNTHESIS' named entity '5-NITROTHIAZOLE' named entity 'TREATMENT' named entity 'SAFETY PHARMACOLOGY' named entity 'COMPLETED' named entity 'AMINO-ACID' named entity 'BROAD' named entity 'VIRUSES' named entity 'SAFETY' named entity 'AUSTRALIA' named entity 'GOOD' named entity 'TOTAL' named entity 'POST' named entity 'SYSTEMIC ABSORPTION' named entity 'ACUTE RESPIRATORY ILLNESS' named entity 'TESTED FOR' named entity 'ANTIPARASITIC AGENT' named entity 'ESTER' named entity 'ITS' named entity 'FOLD' named entity 'CHLORO' named entity 'NITAZOXANIDE' named entity 'PARAMYXOVIRIDAE' named entity 'AMINO' named entity 'CLINICAL TRIALS' named entity 'RESPIRATORY VIRUSES' named entity 'RECENTLY' named entity 'ACTION' named entity 'GASTRO-INTESTINAL' named entity 'VIRAL' named entity 'GENERATION' named entity 'SECOND' named entity 'PRODRUG' named entity 'BLOOD CONCENTRATION' named entity 'ABSOLUTE BIOAVAILABILITY' named entity 'INTESTINAL TRACT' named entity 'PROFILE' named entity 'PHASE II' named entity 'ANTIVIRAL AGENTS' named entity 'PRODRUGS' named entity 'PRE-CLINICAL' named entity 'TIZOXANIDE' named entity 'MECHANISMS' named entity 'BACTERIA ' named entity 'BETTER' named entity 'NEW ZEALAND' named entity 'CANADA' named entity 'SEEN' named entity 'HIGH' named entity 'REPORTED' named entity 'NEEDED' named entity 'INCREASED' named entity 'ORAL' named entity 'RATS' named entity 'PHARMACOLOGY' named entity 'ESTER' named entity 'NEW' named entity 'ADULTS' named entity 'PHARMACOLOGY AND TOXICOLOGY' named entity 'ACETYL' named entity 'ORDER' named entity 'LATER' named entity 'ORTHOMYXOVIRIDAE' named entity 'LEVEL'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software