Tag: 300-400

A cell-based assay to discover inhibitors of SARS-CoV-2 RNA dependent RNA polymerase was written by Zhao, Jianyuan;Guo, SaiSai;Yi, Dongrong;Li, Quanjie;Ma, Ling;Zhang, Yongxin;Wang, Jing;Li, Xiaoyu;Guo, Fei;Lin, Rongtuan;Liang, Chen;Liu, Zhenlong;Cen, Shan. And the article was included in Antiviral Research in 2021.Related Products of 2492423-29-5 The following contents are mentioned in the article:

Antiviral therapeutics is one effective avenue to control and end this devastating COVID-19 pandemic. The viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 has been recognized as a valuable target of antivirals. However, the cell-free SARS-CoV-2 RdRp biochem. assay requires the conversion of nucleotide prodrugs into the active triphosphate forms, which regularly occurs in cells yet is a complicated multiple-step chem. process in vitro, and thus hinders the utility of this cell-free assay in the rapid discovery of RdRp inhibitors. In addition, SARS-CoV-2 exoribonuclease provides the proof-reading capacity to viral RdRp, thus creates relatively high resistance threshold of viral RdRp to nucleotide analog inhibitors, which must be examined and evaluated in the development of this class of antivirals. Here, the authors report a cell-based assay to evaluate the efficacy of nucleotide analog compounds against SARS-CoV-2 RdRp and assess their tolerance to viral exoribonuclease-mediated proof-reading. By testing seven commonly used nucleotide analog viral polymerase inhibitors, Remdesivir, Molnupiravir, Ribavirin, Favipiravir, Penciclovir, Entecavir and Tenofovir, the authors found that both Molnupiravir and Remdesivir showed the strong inhibition of SARS-CoV-2 RdRp, with EC₅₀ value of 0.22μM and 0.67μM, resp. Moreover, the authors’ results suggested that exoribonuclease nsp14 increases resistance of SARS-CoV-2 RdRp to nucleotide analog inhibitors. The authors also determined that Remdesivir presented the highest resistance to viral exoribonuclease activity in cells. Therefore, the authors have developed a cell-based SARS-CoV-2 RdRp assay which can be deployed to discover SARS-CoV-2 RdRp inhibitors that are urgently needed to treat COVID-19 patients. 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: 2492423-29-5Related Products of 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. Solid acid catalysis, and the advantages often associated with their use, have been proved equally efficient for the synthesis of tetrahydrofurans or furans. Tetrahydrofuran reaction with hydrogen sulfide: In the presence of a solid acid catalyst, tetrahydrofuran reacts with hydrogen sulfide to give tetrahydrothiophene.Related Products of 2492423-29-5

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

5′-Iodotubercidin represses insulinoma-associated-1 expression, decreases cAMP levels, and suppresses human neuroblastoma cell growth was written by Chen, Chiachen;Breslin, Mary Beth;Guidry, Jessie J.;Lan, Michael S.. And the article was included in Journal of Biological Chemistry in 2019.Category: tetrahydrofurans The following contents are mentioned in the article:

Insulinoma-associated-1 (INSM1) is a key protein functioning as a transcriptional repressor in neuroendocrine differentiation and is activated by N-Myc in human neuroblastoma (NB). INSM1 modulates the phosphoinositide 3-kinase (PI3K)-AKT Ser/Thr kinase (AKT)-glycogen synthase kinase 3β (GSK3β) signaling pathway through a pos.-feedback loop, resulting in N-Myc stabilization. Accordingly, INSM1 has emerged as a critical player closely associated with N-Myc in facilitating NB cell growth. Here, an INSM1 promoter-driven luciferase-based screen revealed that the compound 5′-iodotubercidin suppresses adenosine kinase (ADK), an energy pathway enzyme, and also INSM1 expression and NB tumor growth. Next, we sought to dissect how the ADK pathway contributes to NB tumor cell growth in the context of INSM1 expression. We also found that 5′-iodotubercidin inhibits INSM1 expression and induces an intra- and extracellular adenosine imbalance. The adenosine imbalance, which triggers adenosine receptor-3 signaling that decreases cAMP levels and AKT phosphorylation and enhances GSK3β activity. We further observed that GSK3β then phosphorylates β-catenin and promotes the cytoplasmic proteasomal degradation pathway. 5′-Iodotubercidin treatment and INSM1 inhibition suppressed extracellular signal-regulated kinase 1/2 (ERK1/2) activity and the AKT signaling pathways required for NB cell proliferation. The 5′-iodotubercidin treatment also suppressed β-catenin, lymphoid enhancer-binding factor 1 (LEF-1), cyclin D1, N-Myc, and INSM1levels, ultimately leading to apoptosis via caspase-3 and p53 activation. The identification of the signaling pathways that control the proliferation of aggressive NB reported here suggests new options for combination treatments of NB patients. This study involved multiple reactions and reactants, such as (2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4Category: tetrahydrofurans).

(2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4) belongs to tetrahydrofuran derivatives. Tetrahydrofurans and furans are important oxygen-containing heterocycles that often exhibit interesting properties for biological applications or applications in the cosmetic industry. Tetrahydrofuran can also be produced, or synthesised, via catalytic hydrogenation of furan. This process involves converting certain sugars into THF by digesting to furfural. An alternative to this method is the catalytic hydrogenation of furan with a nickel catalyst.Category: tetrahydrofurans

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

Disease-drug and drug-drug interaction in COVID-19: Risk and assessment was written by Kumar, Devendra;Trivedi, Neerja. And the article was included in Biomedicine & Pharmacotherapy in 2021.SDS of cas: 2492423-29-5 The following contents are mentioned in the article:

A review. COVID-19 is announced as a global pandemic in 2020. Its mortality and morbidity rate are rapidly increasing, with limited medications. The emergent outbreak of COVID-19 prompted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps spreading. In this infection, a patient’s immune response plays pivotal role in the pathogenesis. This inflammatory factor was shown by its mediators that, in severe cases, reach the cytokine at peaks. Hyperinflammatory state may sparks significant imbalances in transporters and drug metabolic machinery, and subsequent alteration of drug pharmacokinetics may result in unexpected therapeutic response. The present scenario has accounted for the requirement for therapeutic opportunities to relive and overcome this pandemic. Despite the diminishing developments of COVID-19, there is no drug still approved to have significant effects with no side effect on the treatment for COVID-19 patients. Based on the evidence, many antiviral and anti-inflammatory drugs have been authorized by the Food and Drug Administration (FDA) to treat the COVID-19 patients even though not knowing the possible drug-drug interactions (DDI). Remdesivir, favipiravir, and molnupiravir are deemed the most hopeful antiviral agents by improving infected patient’s health. Dexamethasone is the first known steroid medicine that saved the lives of seriously ill patients. Some oligopeptides and proteins have also been using. The current review summarizes medication updates to treat COVID-19 patients in an inflammatory state and their interaction with drug transporters and drug-metabolizing enzymes. It gives an opinion on the potential DDI that may permit the individualization of these drugs, thereby enhancing the safety and efficacy. 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: 2492423-29-5SDS of cas: 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 and dihydrofuran form the basic structural unit of many naturally occurring scaffolds like gambieric acid A and ciguatoxin, goniocin, and some biologically active molecules. Tetrahydrofuran (THF) is primarily used as a precursor to polymers including for surface coating, adhesives, and printing inks.SDS of cas: 2492423-29-5

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

Remdesivir and EIDD-1931 interact with human equilibrative nucleoside transporters 1 and 2: implications for reaching SARS-CoV-2 viral sanctuary sites was written by Miller, Siennah R.;McGrath, Meghan E.;Zorn, Kimberley M.;Ekins, Sean;Wright, Stephen H.;Cherrington, Nathan J.. And the article was included in Molecular Pharmacology in 2021.COA of Formula: C13H19N3O7 The following contents are mentioned in the article:

Equilibrative nucleoside transporters (ENTs) are present at the blood-testis barrier (BTB), where they can facilitate antiviral drug disposition to eliminate a sanctuary site for viruses detectable in semen. The purpose of this study was to investigate ENT-drug interactions with three nucleoside analogs, remdesivir, molnupiravir, and molnupiravir’s active metabolite, β-d-N4-hydroxycytidine (EIDD-1931), and four non-nucleoside mols. repurposed as antivirals for coronavirus disease 2019 (COVID-19). The study used three-dimensional pharmacophores for ENT1 and ENT2 substrates and inhibitors and Bayesian machine learning models to identify potential interactions with these transporters. In vitro transport experiments demonstrated that remdesivir was the most potent inhibitor of ENT-mediated [3H]uridine uptake (ENT1 IC50: 39μM; ENT2 IC50: 77μM), followed by EIDD-1931 (ENT1 IC50: 259μM; ENT2 IC50: 467μM), whereas molnupiravir was a modest inhibitor (ENT1 IC50: 701μM; ENT2 IC50: 851μM). Other proposed antivirals failed to inhibit ENT-mediated [3H]uridine uptake below 1 mM. Remdesivir accumulation decreased in the presence of 6-S-[(4-nitrophenyl)methyl]-6-thioinosine (NBMPR) by 30% in ENT1 cells (P = 0.0248) and 27% in ENT2 cells (P = 0.0054). EIDD-1931 accumulation decreased in the presence of NBMPR by 77% in ENT1 cells (P = 0.0463) and by 64% in ENT2 cells (P = 0.0132), which supported computational predictions that both are ENT substrates that may be important for efficacy against COVID-19. NBMPR failed to decrease molnupiravir uptake, suggesting that ENT interaction is likely inhibitory. Our combined computational and in vitro data can be used to identify addnl. ENT-drug interactions to improve our understanding of drugs that can circumvent the BTB. 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: 2492423-29-5COA of Formula: C13H19N3O7).

((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 can also be synthesized by catalytic hydrogenation of furan. This allows certain sugars to be converted to THF via acid-catalyzed digestion to furfural and decarbonylation to furan, although this method is not widely practiced. THF is thus derivable from renewable resources.COA of Formula: C13H19N3O7

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

Anti-viral treatment for SARS-CoV-2 infection: A race against time amidst the ongoing pandemic was written by Vallianou, Natalia G.;Tsilingiris, Dimitrios;Christodoulatos, Gerasimos Socrates;Karampela, Ιrene;Dalamaga, Maria. And the article was included in Metabolism Open in 2021.Synthetic Route of C13H19N3O7 The following contents are mentioned in the article:

A review. Remdesivir (GS-5734), a drug initially developed to treat hepatitis C and Ebola virus disease, was the first approved treatment for severe coronavirus disease 2019 (COVID-19). However, apart from remdesivir, there is a paucity of other specific anti-viral agents against SARS-CoV-2 infection. In 2017, researchers had documented the anti-coronavirus potential of remdesivir in animal models. At the same time, trials performed during two Ebola outbreaks in Africa showed that the drug was safe. Although vaccines against SARS-CoV-2 infection have emerged at an enormously high speed, equivalent results from efforts towards the development of anti-viral drugs, which could have played a truly life-saving role in the current stage of the pandemic, have been stagnating. In this review, we will focus on the current treatment options for COVID-19 which mainly consist of repurposed agents or treatments conferring passive immunity (convalescent plasma or monoclonal antibodies). Addnl., potential specific anti-viral therapies under development will be reviewed, such as the decoy miniprotein CTC-445.2d, protease inhibitors, mainly against the Main protein Mpro, nucleoside analogs, such as molnupiravir and compounds blocking the replication transcription complex proteins, such as zotatifin and plitidepsin. These anti-viral agents seem to be very promising but still require meticulous clin. trial testing in order to establish their efficacy and safety. The continuous emergence of viral variants may pose a real challenge to the scientific community towards that end. In this context, the advent of nanobodies together with the potential administration of a combination of anti-viral drugs could serve as useful tools in the armamentarium against COVID-19. 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: 2492423-29-5Synthetic Route of C13H19N3O7).

((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. Tetrahydrofurans and furans are important oxygen-containing heterocycles that often exhibit interesting properties for biological applications or applications in the cosmetic industry. Tetrahydrofuran can also be produced, or synthesised, via catalytic hydrogenation of furan. This process involves converting certain sugars into THF by digesting to furfural. An alternative to this method is the catalytic hydrogenation of furan with a nickel catalyst.Synthetic Route of C13H19N3O7

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

Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity was written by Meng, Bo;Abdullahi, Adam;Ferreira, Isabella A. T. M.;Goonawardane, Niluka;Saito, Akatsuki;Kimura, Izumi;Yamasoba, Daichi;Gerber, Pehuen Pereyra;Fatihi, Saman;Rathore, Surabhi;Zepeda, Samantha K.;Papa, Guido;Kemp, Steven A.;Ikeda, Terumasa;Toyoda, Mako;Tan, Toong Seng;Kuramochi, Jin;Mitsunaga, Shigeki;Ueno, Takamasa;Shirakawa, Kotaro;Takaori-Kondo, Akifumi;Brevini, Teresa;Mallery, Donna L.;Charles, Oscar J.;Bowen, John E.;Joshi, Anshu;Walls, Alexandra C.;Jackson, Laurelle;Martin, Darren;Smith, Kenneth G. C.;Bradley, John;Briggs, John A. G.;Choi, Jinwook;Madissoon, Elo;Meyer, Kerstin B.;Mlcochova, Petra;Ceron-Gutierrez, Lourdes;Doffinger, Rainer;Teichmann, Sarah A.;Fisher, Andrew J.;Pizzuto, Matteo S.;de Marco, Anna;Corti, Davide;Hosmillo, Myra;Lee, Joo Hyeon;James, Leo C.;Thukral, Lipi;Veesler, David;Sigal, Alex;Sampaziotis, Fotios;Goodfellow, Ian G.;Matheson, Nicholas J.;Sato, Kei;Gupta, Ravindra K.. And the article was included in Nature (London, United Kingdom) in 2022.Product Details of 2492423-29-5 The following contents are mentioned in the article:

The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis. 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: 2492423-29-5Product Details of 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. THF (Tetrahydrofuran) is a stable compound with relatively low boiling point and excellent solvency. Tetrahydrofuran reaction with hydrogen sulfide: In the presence of a solid acid catalyst, tetrahydrofuran reacts with hydrogen sulfide to give tetrahydrothiophene.Product Details of 2492423-29-5

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

The pill of recovery; Molnupiravir for treatment of COVID-19 patients; a systematic review was written by Kamal, Lina;Ramadan, Ahmed;Farraj, Suha;Bahig, Lydia;Ezzat, Sameera. And the article was included in Saudi Pharmaceutical Journal in 2022.HPLC of Formula: 2492423-29-5 The following contents are mentioned in the article:

A review. Throughout the time of the global pandemic of SARS-CoV-2 virus, there has been a compelling necessity for the development of effective antiviral agents and prophylactic vaccines to limit the virus spread, disease burden, hospitalization, and mortality. Until mid of 2021, the NIH treatment guideline declared no single oral therapy was proven to treat mild to moderate cases. A new hope arose when a repurposed direct acting oral anti-viral agent “Molnupiravir” was shown to be effective in decreasing mortality and need for hospitalization in mild to moderate cases with relatively good safety profile; exhibiting a significant reduction in virus titers only after two days from administration. Molnupiravir was recently granted the FDA emergency use authorization to treat mild to moderate COVID-19 patients with at least one risk factor for progression. We performed a computer-based literature search of (PubMed, Science direct, MedRxiv, BioRxiv, ClinicalTrials.gov, ISRCTN, Cochrane COVID study register, EU registry, and CTRI registry) till Feb. 15th, 2022. The following keywords were used in our search (“Molnupiravir”, “NHC”, “EIDD-2807”, “MK-4482” or “EIDD-1931”). We identified from the initial search a total of 279 articles; 246 articles (BioRxiv and MedRxiv N = 186, PubMed N = 33, Science direct N = 27) and 33 Clin. trials from the following registries (ISCTRN (N = 1), Clin. Trials.gov (N = 6), CTRI (N = 12), Cochrane (N = 14)). Through screening phases, 21 records were removed as duplicates and 198 irrelevant records were also excluded. The included studies in this systematic review were (N = 60) included 39 published papers and 21 clin. trials. After Manual addition (N = 4), the qual. assessment included (N = 64). Based on the cumulative evidence from preclin. and clin. studies, Molnupiravir is proven to be a well tolerated, direct acting oral anti-viral agent to halt the disease progression in mild to moderate COVID-19 cases in terms of mortality and hospitalization rates. 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. THF (Tetrahydrofuran) is a stable compound with relatively low boiling point and excellent solvency. Tetrahydrofuran (THF) is primarily used as a precursor to polymers including for surface coating, adhesives, and printing inks.HPLC of Formula: 2492423-29-5

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

Transient use of a systemic adenosine kinase inhibitor attenuates epilepsy development in mice was written by Sandau, Ursula S.;Yahya, Mayadah;Bigej, Ryan;Friedman, Joseph L.;Saleumvong, Bounmy;Boison, Detlev. And the article was included in Epilepsia in 2019.HPLC of Formula: 24386-93-4 The following contents are mentioned in the article:

Over one-third of all patients with epilepsy are refractory to treatment and there is an urgent need to develop new drugs that can prevent the development and progression of epilepsy. Epileptogenesis is characterized by distinct histopathol. and biochem. changes, which include astrogliosis and increased expression of the adenosine-metabolizing enzyme adenosine kinase (ADK; EC 2.7.1.20). Increased expression of ADK contributes to epileptogenesis and is therefore a target for therapeutic intervention. We tested the prediction that the transient use of an ADK inhibitor administered during the latent phase of epileptogenesis can mitigate the development of epilepsy. We used the intrahippocampal kainic acid (KA) mouse model of temporal lobe epilepsy, which is characterized by ipsilateral hippocampal sclerosis with granule cell dispersion and the development of recurrent hippocampal paroxysmal discharges (HPDs). KA-injected mice were treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 1.6 mg/kg, b.i.d., i.p.) during the latent phase of epileptogenesis from day 3-8 after injury; the period when gradual increases in hippocampal ADK expression begin to manifest. HPDs were assessed at 6 and 9 wk after KA administration followed by epilepsy histopathol. including assessment of granule cell dispersion, astrogliosis, and ADK expression. 5-ITU significantly reduced the percent time in seizures by at least 80% in 56% of mice at 6 wk post-KA. This reduction in seizure activity was maintained in 40% of 5-ITU-treated mice at 9 wk. 5-ITU also suppressed granule cell dispersion and prevented maladaptive ADK increases in these protected mice. Our results show that the transient use of a small-mol. ADK inhibitor, given during the early stages of epileptogenesis, has antiepileptogenic disease-modifying properties, which provides the rationale for further investigation into the development of a novel class of antiepileptogenic ADK inhibitors with increased efficacy for epilepsy prevention. This study involved multiple reactions and reactants, such as (2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4HPLC of Formula: 24386-93-4).

(2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4) belongs to tetrahydrofuran derivatives. THF (Tetrahydrofuran) is water-miscible and has a low viscosity making it a highly versatile solvent used in a variety of industries. Tetrahydrofuran (THF) is primarily used as a precursor to polymers including for surface coating, adhesives, and printing inks.HPLC of Formula: 24386-93-4

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

Catecholamine biosynthesis and secretion: physiological and pharmacological effects of secretin was written by Mahata, Manjula;Zhang, Kuizing;Gayen, Jiaur R.;Nandi, Suvobroto;Brar, Bhawanjit K.;Ghosh, Sajalendu;Mahapatra, Nitish R.;Taupenot, Laurent;O’Connor, Daniel T.;Mahata, Sushil K.. And the article was included in Cell & Tissue Research in 2011.HPLC of Formula: 24386-93-4 The following contents are mentioned in the article:

Pituitary adenylyl cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) augment the biosynthesis of tyrosine hydroxylase (TH). We tested whether secretin belonging to the glucagon/PACAP/VIP superfamily would increase transcription of the tyrosine hydroxylase (Th) gene and modulate catecholamine secretion. Secretin activated transcription of the endogenous Th gene and its transfected promoter (EC₅₀ ∼4.6 nM) in pheochromocytoma (PC12) cells. This was abolished by pre-treatment with a secretin receptor (SCTR) antagonist and by inhibition of protein kinase A (PKA), mitogen-activated protein kinase, or CREB (cAMP response element-binding protein). In agreement, secretin increased PKA activity and induced phosphorylation of CREB and binding to Th CRE, suggesting secretin signaling to transcription via a PKA-CREB pathway. Secretin stimulated catecholamine secretion (EC₅₀ ∼3.5 μM) from PC12 cells, but this was inhibited by pre-treatment with VIP-preferring receptor (VPAC1)/PACAP-preferring receptor (PAC1) antagonists. Secretin-evoked secretion occurred without extracellular Ca²⁺ and was abolished by intracellular Ca²⁺ chelation. Secretin augmented phospholipase C (PLC) activity and increased inositol-1,4,5-triphosphate (IP₃) levels in PC12 cells; PLC-β inhibition blocked secretin-induced catecholamine secretion, indicating the participation of intracellular Ca²⁺ from a phospholipase pathway in secretion. Like PACAP, secretin evoked long-lasting catecholamine secretion, even after only a transient exposure. Thus, transcription is triggered by nanomolar concentrations of the peptide through SCTR, with signaling along the cAMP-PKA and extracellular-signal-regulated kinase 1/2 pathways and through CREB. By contrast, secretion is triggered only by micromolar concentrations of peptide through PAC1/VPAC receptors and by utilizing a PLC/intracellular Ca²⁺ pathway. This study involved multiple reactions and reactants, such as (2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4HPLC of Formula: 24386-93-4).

(2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4) 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 can also be produced, or synthesised, via catalytic hydrogenation of furan. This process involves converting certain sugars into THF by digesting to furfural. An alternative to this method is the catalytic hydrogenation of furan with a nickel catalyst.HPLC of Formula: 24386-93-4

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

Constrained NBMPR analogue synthesis, pharmacophore mapping and 3D-QSAR modeling of equilibrative nucleoside transporter 1 (ENT1) inhibitory activity was written by Zhu, Zhengxiang;Buolamwini, John K.. And the article was included in Bioorganic & Medicinal Chemistry in 2008.Electric Literature of C11H13IN4O4 The following contents are mentioned in the article:

Conformationally constrained analog synthesis was undertaken to aid in pharmacophore mapping and 3D-QSAR anal. of nitrobenzylmercaptopurine riboside (NBMPR) congeners as equilibrative nucleoside transporter 1 (ENT1) inhibitors. In our previous study, novel regioisomeric nitro-1,2,3,4-tetrahydroisoquinoline conformationally constrained analogs of NBMPR were synthesized and evaluated as ENT1 ligands. 7-NO₂-1,2,3,4-Tetrahydroisoquino-2-yl purine riboside was identified as the analog with the nitro group in the best orientation at the NBMPR binding site of ENT1. In the present study, further conformational constraining was introduced by synthesizing 5′-O,8-cyclo derivatives The flow cytometrically determined binding affinities indicated that the addnl. 5′-O,8-cyclo constraining was unfavorable for binding to the ENT1 transporter. The structure-activity relation (SAR) acquired was applied to pharmacophore mapping using the PHASE program. The best pharmacophore hypothesis obtained embodied an anti-conformation with three hydrogen-bond acceptors, one hydrophobic center, and two aromatic rings involving the 3′-OH, 4′-oxygen, the NO₂ group, the benzyl Ph and the imidazole and pyrimidine portions of the purine ring, resp. A PHASE 3D-QSAR model derived with this pharmacophore yielded an r² of 0.916 for four (4) PLS components, and an excellent external test set predictive r² of 0.78 for 39 compounds This pharmacophore was used for mol. alignment in a comparative mol. field anal. (CoMFA) 3D-QSAR study that also afforded a predictive model with external test set validation predictive r² of 0.73. Thus, although limited, this study suggests that the bioactive conformation for NBMPR at the ENT1 transporter could be anti. The study has also suggested an ENT1 inhibitory pharmacophore, and established a predictive CoMFA 3D-QSAR model that might be useful for novel ENT1 inhibitor discovery and optimization. This study involved multiple reactions and reactants, such as (2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4Electric Literature of C11H13IN4O4).

(2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4) belongs to tetrahydrofuran derivatives. Tetrahydrofurans and furans are important oxygen-containing heterocycles that often exhibit interesting properties for biological applications or applications in the cosmetic industry. THF (Tetrahydrofuran) is also used as a starting material for the synthesis of poly(tetramethylene ether) glycol (PTMG), etc.Electric Literature of C11H13IN4O4

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