Day: February 22, 2023

[3a,4]-Dihydropyrazolo[1,5a]pyrimidines: Novel, Potent, and Selective Phosphatidylinositol-3-kinase 尾 Inhibitors was written by Yu, Hongyi;Moore, Michael L.;Erhard, Karl;Hardwicke, Mary Ann;Lin, Hong;Luengo, Juan I.;McSurdy-Freed, Jeanelle;Plant, Ramona;Qu, Junya;Raha, Kaushik;Rominger, Cynthia M.;Schaber, Michael D.;Spengler, Michael D.;Rivero, Ralph A.. And the article was included in ACS Medicinal Chemistry Letters in 2013.Application In Synthesis of Ethyl 3-Oxo-3-(4-tetrahydropyranyl)propanoate This article mentions the following:

A series of novel [3a,4]dihydropyrazolo[1,5a]pyrimidines were identified, which were highly potent and selective inhibitors of PI3K尾 (e.g., I). The template afforded the opportunity to develop novel SAR for both the hinge-binding (morpholino) and back-pocket (OH) substituents. While cellular potency was relatively modest due to high protein binding, the series displayed low clearance in rat, mouse, and monkey. In the experiment, the researchers used many compounds, for example, Ethyl 3-Oxo-3-(4-tetrahydropyranyl)propanoate (cas: 856414-68-1Application In Synthesis of Ethyl 3-Oxo-3-(4-tetrahydropyranyl)propanoate).

Ethyl 3-Oxo-3-(4-tetrahydropyranyl)propanoate (cas: 856414-68-1) belongs to tetrahydropyran derivatives. Tetrahydropyrans are also used as important solvents, as chemical intermediate and as monomer for ring-opening polymerization. The reaction of tertiary 1,4- and 1,5-diols with cerium ammonium nitrate at room temperature gives tetrahydrofuran and tetrahydropyran derivatives in high yield and stereoselectivity. Various fragrant compounds have been synthesized using this method.Application In Synthesis of Ethyl 3-Oxo-3-(4-tetrahydropyranyl)propanoate

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

Discovery of a Selective, Covalent IRAK1 Inhibitor with Antiproliferative Activity in MYD88 Mutated B-Cell Lymphoma was written by Hatcher, John M.;Yang, Guang;Wang, Li;Ficarro, Scott B.;Buhrlage, Sara;Wu, Hao;Marto, Jarrod A.;Treon, Steven P.;Gray, Nathanael S.. And the article was included in ACS Medicinal Chemistry Letters in 2020.Reference of 903550-26-5 This article mentions the following:

Interleukin 1 (IL-1) receptor-associated kinases (IRAKs) are serine/threonine kinases that play critical roles in initiating the innate immune response against foreign pathogens. Addnl., dysregulation of IRAK1 signaling plays a role in neoplastic disorders. For example, IRAK1 was shown to be important for survival and proliferation in many B-cell lymphomas, including Waldenstr枚m’s macroglobulinemia (WM) and ABC subtype Diffused Large B-cell Lymphoma (DLBCL) cells. Here, we report the discovery of a highly potent and selective covalent inhibitor of IRAK1, JH-X-119-01. Intact protein MS labeling studies confirmed that JH-X-119-01 irreversibly labels IRAK1 at C302. This compound exhibited cytotoxic activity at single digit micromolar concentrations in a panel of WM, DLBCL, and lymphoma cell lines expressing MYD88. Cotreatment of JH-X-119-01 with the BTK inhibitor ibrutinib resulted in synergistic killing effects in these systems. Taken together, JH-X-119-01 represents a highly selective probe of IRAK1 for further development. In the experiment, the researchers used many compounds, for example, 1-(Tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (cas: 903550-26-5Reference of 903550-26-5).

1-(Tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (cas: 903550-26-5) belongs to tetrahydropyran derivatives. Tetrahydropyrans and furans principally constitute as a central motif in diverse medicinally privileged molecules. The most notable anticancer agent, bryostatin, and eribulin are marine macrolides having intriguing tetrahydropyran and furan motif. Reference of 903550-26-5

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

Therapeutic vs. suprapharmacological metformin concentrations: different effects on energy metabolism and mitochondrial function in skeletal muscle cells in vitro was written by Pavlovic, Kasja;Jakovljevic, Nina Krako;Isakovic, Andjelka M.;Ivanovic, Tijana;Markovic, Ivanka;Lalic, Nebojsa M.. And the article was included in Frontiers in Pharmacology in 2022.Application of 11024-24-1 This article mentions the following:

Metformin is an oral antidiabetic agent that has been widely used in clin. practice for over 60 years, and is currently the most prescribed antidiabetic drug worldwide. However, the mol. mechanisms of metformin action in different tissues are still not completely understood. Although metformin-induced inhibition of mitochondrial respiratory chain Complex I and activation of AMP-activated protein kinase have been observed in many studies, published data is inconsistent. Furthermore, metformin concentrations used for in vitro studies and their pharmacol. relevance are a common point of debate. The aim of this study was to explore the effects of different metformin concentrations on energy metabolism and activity of relevant signaling pathways in C2C12 muscle cells in vitro. In order to determine if therapeutic metformin concentrations have an effect on skeletal muscle cells, we used micromolar metformin concentrations (50 渭M), and compared the effects with those of higher, millimolar concentrations (5 mM), that have already been established to affect mitochondrial function and AMPK activity. We conducted all experiments in conditions of high (25 mM) and low glucose (5.5 mM) concentration, in order to discern the role of glucose availability on metformin action. According to our results, micromolar metformin treatment did not cause Complex I inhibition nor AMPK activation. Also, cells cultured in low glucose medium were more sensitive to Complex I inhibition, mitochondrial membrane depolarization and AMPK activation by millimolar metformin, but cells cultured in high glucose medium were more prone to induction of ROS production In conclusion, even though suprapharmacol. metformin concentrations cause Complex I inhibition and AMPK activation in skeletal muscle cells in vitro, therapeutic concentrations cause no such effect. This raises the question if these mechanisms are relevant for therapeutic effects of metformin in skeletal muscle. In the experiment, the researchers used many compounds, for example, Digitonin (cas: 11024-24-1Application of 11024-24-1).

Digitonin (cas: 11024-24-1) belongs to tetrahydropyran derivatives. Tetrahydropyrans and furans principally constitute as a central motif in diverse medicinally privileged molecules. 2-(Arylmethylene)cyclopropylcarbinols could be converted to the corresponding tetrahydropyrans stereoselectively in the presence of Br酶nsted acids under mild conditions. A plausible Prins-type reaction mechanism has been proposed.Application of 11024-24-1

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

A Comparative Study of Chemical Profiling and Biological Effects of Doronicum orientale Extracts was written by Zengin, Gokhan;Mahoomodally, Mohamad Fawzi;Sinan, Kouadio Ibrahime;Bakar, Kassim;Jugreet, Sharmeen;Yildiztugay, Evren;Angeloni, Simone;Mustafa, Ahmed M.;Caprioli, Giovanni. And the article was included in Chemistry & Biodiversity in 2022.Recommanded Product: (4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one This article mentions the following:

In this study, phytochem. and pharmacol. screening of the aerial part and roots extracts from Doronicum orientale Hoffm. (Asteraceae) was carried out. Plant extracts were obtained using solvents of different polarity (hexane, Et acetate, ethanol, ethanol/water, water) for selection the most optimal solvent for the extraction of active compounds For instance, the extracts yielded total phenolic and flavonoid contents in the range of 12.13-45.67 mg GAE/g and 0.75-12.44 mg QE/g, resp., while the total antioxidant capacity of the extracts determined by the phosphomolybdenum assay ranged from 0.88-2.53 mmol TE/g. HPLC/MS/MS anal. revealed 5-caffeoylquinic acid (2.52-337.05渭g/g) and 3,5-dicaffeoylquinic acid (3.12-299.36渭g/g) to be the major components present in the investigated extracts Antioxidant activity in terms of radical scavenging ability of the extracts ranged from 0.82-45.56 mg TE/g in DPPH assay and from 5.07-104.58 mg TE/g in ABTS assay. The tested extracts were found to inhibit acetylcholinesterase (aerial part: 0.50-2.33 mg GALAE/g; roots: 0.40-2.43 mg GALAE/g), while with the exception of the water extracts, the other extracts showed butyrylcholinesterase inhibition (aerial part: 2.46-5.02 mg GALAE/g; root: 2.93-4.17 mg GALAE/g). Overall, this study presented an interesting scope of this species in phytomedicine with preliminary data demonstrating some of the tested extracts to possess high bioactive contents, antioxidant potential and enzyme inhibitory activity. Thus, addnl. investigations are necessary to confirm their safety in herbal drug applications. In the experiment, the researchers used many compounds, for example, (4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one (cas: 17388-39-5Recommanded Product: (4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one).

(4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one (cas: 17388-39-5) belongs to tetrahydropyran derivatives. Tetrahydropyrans are useful synthons for biologically important compounds. Pyran derivatives such as pyran flavonoids are biologically important. Monosaccharides containing six-membered rings are called pyranose.Recommanded Product: (4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

A Rh(I)-catalyzed cycloisomerization reaction affording cyclic trienones was written by Brummond, Kay M.;Chen, Daitao;Painter, Thomas O.;Mao, Shuli;Seifried, Darla D.. And the article was included in Synlett in 2008.Quality Control of 2-(But-3-yn-1-yloxy)tetrahydro-2H-pyran This article mentions the following:

A Rh(I)-catalyzed carbocyclization reaction of allene-ynones affords functionalized 2-alkylidene-3-vinylcyclohexenones and -cyclopentenones. The scope, limitations, and utility of this triene-forming protocol were examined In the experiment, the researchers used many compounds, for example, 2-(But-3-yn-1-yloxy)tetrahydro-2H-pyran (cas: 40365-61-5Quality Control of 2-(But-3-yn-1-yloxy)tetrahydro-2H-pyran).

2-(But-3-yn-1-yloxy)tetrahydro-2H-pyran (cas: 40365-61-5) belongs to tetrahydropyran derivatives. Tetrahydropyran is a useful synthetic intermediate. Tetrahydropyranyl (THP-) ethers derived from the reaction of alcohols and dihydropyran are common intermediates in organic synthesis. The reaction of tertiary 1,4- and 1,5-diols with cerium ammonium nitrate at room temperature gives tetrahydrofuran and tetrahydropyran derivatives in high yield and stereoselectivity. Various fragrant compounds have been synthesized using this method.Quality Control of 2-(But-3-yn-1-yloxy)tetrahydro-2H-pyran

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

A proposed protocol based on integrative metabonomics analysis for the rapid detection and mechanistic understanding of sulfur fumigation of Chinese herbal medicines was written by Dai, Shengyun;Wang, Yuqi;Fei, Wang;Mei, Xiaodan;Zhang, Jiayu. And the article was included in RSC Advances in 2019.Application In Synthesis of (4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one This article mentions the following:

In the current work, Lonicera japonica Flos (FLJ) was selected as a model Chinese herbal medicine (CHM) and a protocol was proposed for the rapid detection of sulfur-fumigated (SF) CHMs. A multiple metabonomics anal. was conducted using HPLC, NIR spectroscopy and a UHPLC-LTQ-Orbitrap mass spectrometer. First, the group discriminatory potential of each technique was resp. investigated based on PCA. Then, the effect of mid-level metabonomics data fusion on sample spatial distribution was evaluated based on data obtained using the above three technologies. Furthermore, based on the acquired HRMS data, 76 markers discriminating SF from non-sulfur-fumigated (NSF) CHMs were observed and 49 of them were eventually characterized. Moreover, NIR absorptions of 18 sulfur-containing markers were identified to be in close correlation with the discriminatory NIR wavebands. In conclusion, the proposed protocol based on integrative metabonomics anal. that we established for the rapid detection and mechanistic explanation of the sulfur fumigation of CHMs was able to achieve variable selection, enhance group separation and reveal the intrinsic mechanism of the sulfur fumigation of CHMs. In the experiment, the researchers used many compounds, for example, (4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one (cas: 17388-39-5Application In Synthesis of (4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one).

(4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one (cas: 17388-39-5) belongs to tetrahydropyran derivatives. Numerous natural products have tetrahydropyran skeleton as the building block for designing new natural products and their derivatives e.g. aplysiatoxins, avermectins, oscillatoxins, talaromycins, latrunculins and acutiphycins. The most notable anticancer agent, bryostatin, and eribulin are marine macrolides having intriguing tetrahydropyran and furan motif. Application In Synthesis of (4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

A yellow fever virus NS4B inhibitor not only suppresses viral replication, but also enhances the virus activation of RIG-I-like receptor-mediated innate immune response was written by Gao, Zhao;Zhang, Xuexiang;Zhang, Lin;Wu, Shuo;Ma, Julia;Wang, Fuxuan;Zhou, Yan;Dai, Xinghong;Bullitt, Esther;Du, Yanming;Guo, Ju-Tao;Chang, Jinhong. And the article was included in PLoS Pathogens in 2022.SDS of cas: 11024-24-1 This article mentions the following:

Flavivirus infection of cells induces massive rearrangements of the endoplasmic reticulum (ER) membrane to form viral replication organelles (ROs) which segregates viral RNA replication intermediates from the cytoplasmic RNA sensors. Among other viral nonstructural (NS) proteins, available evidence suggests for a prominent role of NS4B, an ER membrane protein with multiple transmembrane domains, in the formation of ROs and the evasion of the innate immune response. We previously reported a benzodiazepine compound, BDAA, which specifically inhibited yellow fever virus (YFV) replication in cultured cells and in vivo in hamsters, with resistant mutation mapped to P219 of NS4B protein. In the following mechanistic studies, we found that BDAA specifically enhances YFV induced inflammatory cytokine response in association with the induction of dramatic structural alteration of ROs and exposure of double-stranded RNA (dsRNA) in virus-infected cells. Interestingly, the BDAA-enhanced cytokine response in YFV-infected cells is attenuated in RIG-I or MAD5 knockout cells and completely abolished in MAVS knockout cells. However, BDAA inhibited YFV replication at a similar extent in the parent cells and cells deficient of RIG-I, MDA5 or MAVS. These results thus provided multiple lines of biol. evidence to support a model that BDAA interaction with NS4B may impair the integrity of YFV ROs, which not only inhibits viral RNA replication, but also promotes the release of viral RNA from ROs, which consequentially activates RIG-I and MDA5. Although the innate immune enhancement activity of BDAA is not required for its antiviral activity in cultured cells, its dual antiviral mechanism is unique among all the reported antiviral agents thus far and warrants further investigation in animal models in future. In the experiment, the researchers used many compounds, for example, Digitonin (cas: 11024-24-1SDS of cas: 11024-24-1).

Digitonin (cas: 11024-24-1) belongs to tetrahydropyran derivatives. Numerous natural products have tetrahydropyran skeleton as the building block for designing new natural products and their derivatives e.g. aplysiatoxins, avermectins, oscillatoxins, talaromycins, latrunculins and acutiphycins. The reaction of tertiary 1,4- and 1,5-diols with cerium ammonium nitrate at room temperature gives tetrahydrofuran and tetrahydropyran derivatives in high yield and stereoselectivity. Various fragrant compounds have been synthesized using this method.SDS of cas: 11024-24-1

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

The consistent force field. 4. An optimized set of potential energy functions for aliphatic and alicyclic ethers and anomeric carbon atoms was written by Fabricius, Jesper;Engelsen, Soeren Balling;Rasmussen, Kjeld. And the article was included in New Journal of Chemistry in 1995.Safety of 2-Methoxytetrahydro-2H-pyran This article mentions the following:

A set of potential energy function parameters has been optimized for the ether oxygen and anomeric carbon atoms. The force field is classical except for the use of Morse functions for bond deformation. Optimization was done on internal mol. structure of gases, unit cell dimensions of crystals, and vibrational spectra of gases using the Consistent Force Field program. A previous work led to optimization of 15 parameters for alkanes. The ether parameter set contains 53 parameters, 38 of which were optimized on a database of 11 gas phase structures and 6 crystal structures, and vibrational spectra of 10 compounds The performance of the resulting force field was checked on substances and properties not included in the optimization: energy barrier data calculated with high-level ab initio methods, exptl. thermodn. data, and supplementary data on internal structure, rotational constants and dipole moments. Change of previous strategy from optimization of at. charge parameters on mol. dipole moments to the fitting of partial charges derived from ab initio studies improves the performance with respect to rotamer energies. With the simple classical force field used and with parameters optimized exclusively on exptl. data, we obtained rotational barriers conforming to recent ab initio studies on 2-methoxytetrahydropyran, a model compound for carbohydrates in general and the exo-anomeric effect in particular. In the experiment, the researchers used many compounds, for example, 2-Methoxytetrahydro-2H-pyran (cas: 6581-66-4Safety of 2-Methoxytetrahydro-2H-pyran).

2-Methoxytetrahydro-2H-pyran (cas: 6581-66-4) belongs to tetrahydropyran derivatives. In organic synthesis, the 2-tetrahydropyranyl group is used as a protecting group for alcohols. The reaction of tertiary 1,4- and 1,5-diols with cerium ammonium nitrate at room temperature gives tetrahydrofuran and tetrahydropyran derivatives in high yield and stereoselectivity. Various fragrant compounds have been synthesized using this method.Safety of 2-Methoxytetrahydro-2H-pyran

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics