Category: 2492423-29-5

Accelerated first-in-human clinical trial of EIDD-2801/MK-4482 (molnupiravir), a ribonucleoside analog with potent antiviral activity against SARS-CoV-2 was written by Holman, Wendy;Holman, Wayne;McIntosh, Stacy;Painter, Wendy;Painter, George;Bush, Jim;Cohen, Oren. And the article was included in Trials in 2021.HPLC of Formula: 2492423-29-5 The following contents are mentioned in the article:

Abstract: A recently published article described the safety, tolerability, and pharmacokinetic profile of molnupiravir (Painter et al. 2021), a novel antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Here, we report an unprecedented collaboration between sponsor, contract research organization (CRO), and regulatory authorities that enabled accelerated generation of these phase I data, including administration of the first-in-human (FIH) dose of molnupiravir within 5 days of receiving regulatory approval in the United Kingdom (UK). Single and multiple ascending dose (SAD and MAD, resp.) cohorts were dosed in randomized, double-blind, and placebo-controlled fashion, with a 6:2 active-to-placebo ratio in each cohort. A food-effect (FE) cohort included 10 subjects who were randomized to receive drug in the fasted or fed state followed by the fed or fasted state to complete a fed and fasted sequence for each subject. Dose escalation decisions were accelerated and MAD cohorts were initiated prior to completion of all SAD cohorts with the provision that the total daily dose in a MAD cohort would not exceed a dose proven to be safe and well-tolerated in a SAD cohort. Dosing in healthy volunteers was completed for eight single ascending dose (SAD) cohorts, seven multiple ascending dose (MAD) cohorts, and one food-effect (FE) cohort within approx. 16 wk of initial protocol submission to the Research Ethics Committee (REC) and Medicines and Healthcare products Regulatory Agency (MHRA). Working to standard industry timelines, the FIH study would have taken approx. 46 wk to complete and 33 wk to enable phase 2 dosing. Data from this study supported submission of a phase 2/3 clin. trial protocol to the US Food and Drug Administration (FDA) within 8 wk of initial protocol submission, with FDA comments permitting phase 2 study initiation within two addnl. weeks. In the setting of a global pandemic, this model of collaboration allows for accelerated generation of clin. data compared to standard processes, without compromising safety. This study involved multiple reactions and reactants, such as ((2R,3S,4R,5R)-3,4-Dihydroxy-5-((Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl isobutyrate (cas: 2492423-29-5HPLC of Formula: 2492423-29-5).

((2R,3S,4R,5R)-3,4-Dihydroxy-5-((Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl isobutyrate (cas: 2492423-29-5) belongs to tetrahydrofuran derivatives.Tetrahydrofuran has many industry uses as a solvent including in natural and synthetic resins, high polymers, fat oils, rubber, polymer. Tetrahydrofuran reaction with hydrogen sulfide: In the presence of a solid acid catalyst, tetrahydrofuran reacts with hydrogen sulfide to give tetrahydrothiophene.HPLC of Formula: 2492423-29-5

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

TMPRSS2, a novel host-directed drug target against SARS-CoV-2 was written by Keller, Christian;Boettcher-Friebertshaeuser, Eva;Lohoff, Michael. And the article was included in Signal Transduction and Targeted Therapy in 2022.Category: tetrahydrofurans The following contents are mentioned in the article:

In a recent study in Nature, Shapira et al. reported that the peptidomimetic compound N-0385 inhibited SARS-CoV-2 infection in vitro in remarkably low concentrations by blocking the host cell protease TMPRSS2, which mediates proteolytic cleavage of the SARS-CoV-2 major surface glycoprotein spike(S). Antigenic escape by, e.g., the Omicron variant (B.1.1.529) may jeopardize passive immunization by monoclonal antibodies, calling for complementary concepts in prophylaxis and therapy. So far, these have concentrated on agents that directly interfere with viral replication, e.g., by inhibition of the viral 3CL proprotease (paxlovid), by inhibition of the RNA-dependent RNA polymerase (remdesivir), or by introducing copying errors (molnupiravir). Viral infection not only requires binding of S to its receptor angiotensin-converting enzyme 2 (ACE2) but also cleavage of S at two distinct sites by host cell proteases: First, furin (and related pro-protein convertases) cleaves at a polybasic site, generating the S1 and S2 subunits, which remainnon-covalently linked (S1/S2 site, Fig.1a). Mechanistically, TMPRSS2 inhibition results in incompletely cleaved, fusion-incompetent SARS-CoV-2 viruses that are unable to infect new host cells (Fig.1a). The data presented by Shapira et al. suggest spike maturation by inhibiting TMPRSS2 as a potent drug target in COVID-19 when the inhibitor is given before or early in infection. As an advantage over virus-directed therapies, host-directed targets have a low potential for resistance: The TMPRSS2 cleavage site of the SARS-CoV-2 spike protein has remained very conserved over the pandemic (Fig.1b), suggesting that N-0385 should retain a high potency against future variants of concern. Another advantage to target TMPRSS2 is its activating function in other viral infections (e.g., other corona viruses, influenza virus), which expands the field of potential applications for TMPRSS2 inhibitors. Broad-spectrum serine protease inhibitors against COVID-19 that were recently evaluated in clin. trials are i.v. nafamostat, a synthetic inhibitor, and aerosolized aprotinin, a protease inhibitor from bovine lung. This study involved multiple reactions and reactants, such as ((2R,3S,4R,5R)-3,4-Dihydroxy-5-((Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl isobutyrate (cas: 2492423-29-5Category: tetrahydrofurans).

((2R,3S,4R,5R)-3,4-Dihydroxy-5-((Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl isobutyrate (cas: 2492423-29-5) belongs to tetrahydrofuran derivatives. THF (Tetrahydrofuran) is a stable compound with relatively low boiling point and excellent solvency. THF (Tetrahydrofuran) is also used as a starting material for the synthesis of poly(tetramethylene ether) glycol (PTMG), etc.Category: tetrahydrofurans

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Response to Dal-Re and Holm’s ethical concern regarding the UK PANORAMIC COVID-19 trial by the PANORAMIC Investigators was written by Butler, Christopher C.;the PANORAMIC Trial Investigators. And the article was included in British Journal of Clinical Pharmacology in 2022.Application In Synthesis of ((2R,3S,4R,5R)-3,4-Dihydroxy-5-((Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl isobutyrate The following contents are mentioned in the article:

In this article the author discusses about response to Dal-Re and Holm’s ethical concern regarding UK PANORAMIC COVID-19 trial by PANORAMIC investigators. All participants are able to receive standard best available care, regardless of whether they are receive an antiviral in PANORAMIC or not. If randomized to an anti-viral arm in PANORAMIC, participants who are eligible for CMDU treatment can also be given a neutralizing monoclonal antibody (nMAB) or an antiviral drug outside of PANORAMIC. This is all at the discretion of the clinician in charge at the CMDU. Similarly, if randomized to Usual Care in PANORAMIC, participants can still receive an nMAB or an antiviral agent from a CMDU. The PANORAMIC Trial Website states that some may be eligible to receive antiviral treatment outside of the PANORAMIC Trial and that their clin. care remains under the direction of the NHS. The CDMUs were established to provide access to acute COVID treatments for the highest risk patients, a much smaller eligible population than all people over 50 or over 18 with a COVID risk factor eligible for PANORAMIC. The care pathways are complementary. Further, highest risk patients have been contacted with advice (and a PCR test kit) how to access a CDMU in the event they become infected and CDMUs are also contacting eligible people at highest risk if they test pos. Molnupiravir has conditional marketing approval in the UK, recognizing that clin. data for full authorization are not yet available. PANORAMIC is a key contribution to generate these data. For example, participants in the pivotal phase 3 trial (MOVe-OUT) were unvaccinated, exposed to different variants of SARs-CoV-2 from those in current circulation, and largely recruited in healthcare systems different from the UK. It is important to evaluate whether the treatment effect on which the conditional approval is based applies in a clin. relevant population in the UK. PANORAMIC thus represents a pragmatic means to assess molnupiravir and other potential treatments without denying participants access to treatments available through other approved routes. This study involved multiple reactions and reactants, such as ((2R,3S,4R,5R)-3,4-Dihydroxy-5-((Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl isobutyrate (cas: 2492423-29-5Application In Synthesis of ((2R,3S,4R,5R)-3,4-Dihydroxy-5-((Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl isobutyrate).

((2R,3S,4R,5R)-3,4-Dihydroxy-5-((Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl isobutyrate (cas: 2492423-29-5) belongs to tetrahydrofuran derivatives. Tetrahydrofuran (THF), or oxolane, is mainly used as a precursor to polymers. Being polar and having a wide liquid range, THF is a versatile solvent. Tetrahydrofuran reaction with hydrogen sulfide: In the presence of a solid acid catalyst, tetrahydrofuran reacts with hydrogen sulfide to give tetrahydrothiophene.Application In Synthesis of ((2R,3S,4R,5R)-3,4-Dihydroxy-5-((Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl isobutyrate

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem