Heterocyclic Building Blocks-Tetrahydropyran

Niyonsaba, Edouard published the artcileDifferentiation of Deprotonated Acyl-, N-, and O-Glucuronide Drug Metabolites by Using Tandem Mass Spectrometry Based on Gas-Phase Ion-Molecule Reactions Followed by Collision-Activated Dissociation, Name: (2S,3S,4S,5R,6S)-3,4,5-Trihydroxy-6-(4-(2-(4-hydroxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-2-carboxylic acid, the publication is Analytical Chemistry (Washington, DC, United States) (2019), 91(17), 11388-11396, database is CAplus and MEDLINE.

Glucuronidation, a common phase II biotransformation reaction, is one of the major in vitro and in vivo metabolism pathways of xenobiotics. In this process, glucuronic acid is conjugated to a drug or a drug metabolite via a carboxylic acid, a hydroxy, or an amino group to form acyl, O-, and/or N-glucuronide metabolites, resp. This process is traditionally thought to be a detoxification pathway. However, some acyl glucuronides react with biomols. in vivo, which may result in immune-mediated idiosyncratic drug toxicity (IDT). In order to avoid this, one may attempt in early drug discovery to modify the lead compounds in such a manner that they then have a lower probability of forming reactive acyl glucuronide metabolites. Because most drugs or drug candidates bear multiple functionalities, e.g., hydroxy, amino, and carboxylic acid groups, glucuronidation can occur at any of those. However, differentiation of isomeric acyl, N- and O-glucuronide derivatives of drugs is challenging. In this study, gas-phase ion-mol. reactions between deprotonated glucuronide metabolites and BF3 followed by collision-activated dissociation (CAD) in a linear quadrupole ion trap mass spectrometer were demonstrated to enable the differentiation of acyl, N-, and O-glucuronides. Only deprotonated N-glucuronides and deprotonated, migrated acyl glucuronides form the two diagnostic product ions: a BF3 adduct that has lost two HF mols., [M – H + BF3-2 HF]-, and an adduct formed with two BF3 mols. that has lost three HF mols., [M – H + 2 BF3-3 HF]-. These product ions were not observed for deprotonated O-glucuronides and unmigrated, deprotonated acyl glucuronides. Upon CAD of the [M – H + 2 BF3-3 HF]- product ion, a diagnostic fragment ion is formed via the loss of 2-fluoro-1,3,2-dioxaborale (MW of 88 Da) only in the case of deprotonated, migrated acyl glucuronides. Therefore, this method can be used to unambiguously differentiate acyl, N- and O-glucuronides. Further, coupling this method-ol. with HPLC enables the differentiation of unmigrated 1-β-acyl glucuronides from the isomeric acyl glucuronides formed upon acyl migration. Quantum chem. calculations at the M06-2X/6-311++G(d,p) level of theory were employed to probe the mechanisms of the reactions of interest.

Analytical Chemistry (Washington, DC, United States) published new progress about 267244-08-6. 267244-08-6 belongs to tetrahydropyran, auxiliary class Tetrahydropyran,Chiral,Carboxylic acid,Benzene,Phenol,Alcohol,Ether,, name is (2S,3S,4S,5R,6S)-3,4,5-Trihydroxy-6-(4-(2-(4-hydroxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-2-carboxylic acid, and the molecular formula is C21H24O8, Name: (2S,3S,4S,5R,6S)-3,4,5-Trihydroxy-6-(4-(2-(4-hydroxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-2-carboxylic acid.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydropyran,
Tetrahydropyran – an overview | ScienceDirect Topics

Cherry, Khalil published the artcileEfficient regio- and stereoselective synthesis of 5-alkyl(aryl)idene- and 5-[iodoalkyl(aryl)idene]-1H-pyrrol-2(5H)-ones via electrophilic cyclization, Quality Control of 27943-46-0, the publication is Synthesis (2009), 257-270, database is CAplus.

A variety of substituted 5-alkyl(aryl)idene- and 5-[iodoalkyl(aryl)idene]-1H-pyrrol-2(5H)-ones were readily prepared with good yields under very mild reaction conditions by the iodocyclization of (2Z,4E)-dienamides and (Z)-alk-2-en-4-ynamides with ICl. 3-Ylidene-isoindolin-1-ones were also synthesized in moderate to good yields under the same conditions. The methodol. proceeded with total regioselectivity in all cases and was applied to the synthesis of new unsaturated lactams.

Synthesis published new progress about 27943-46-0. 27943-46-0 belongs to tetrahydropyran, auxiliary class Tetrahydropyran,Alkynyl,Ether, name is 2-((2-Methylbut-3-yn-2-yl)oxy)tetrahydro-2H-pyran, and the molecular formula is C10H16O2, Quality Control of 27943-46-0.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydropyran,
Tetrahydropyran – an overview | ScienceDirect Topics

Kothandaraman, Shankaran published the artcileDesign, synthesis, and structure-activity relationship of novel CCR2 antagonists, Category: tetrahydropyran, the publication is Bioorganic & Medicinal Chemistry Letters (2009), 19(6), 1830-1834, database is CAplus and MEDLINE.

A series of novel 1-aminocyclopentyl-3-carboxamides incorporating substituted tetrahydropyran moieties have been synthesized and evaluated for their antagonistic activity against the human CCR2 receptor. Among them analog I was found to posses potent antagonistic activity.

Bioorganic & Medicinal Chemistry Letters published new progress about 624734-19-6. 624734-19-6 belongs to tetrahydropyran, auxiliary class Tetrahydropyran,Fluoride,Ketone, name is 3-Fluorodihydro-2H-pyran-4(3H)-one, and the molecular formula is C5H7FO2, Category: tetrahydropyran.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydropyran,
Tetrahydropyran – an overview | ScienceDirect Topics

Pottenger, Lynn H. published the artcileThe relative bioavailability and metabolism of bisphenol A in rats is dependent upon the route of administration, Category: tetrahydropyran, the publication is Toxicological Sciences (2000), 54(1), 3-18, database is CAplus and MEDLINE.

Bisphenol A (BPA) is used to produce polymers for food contact applications, thus there is potential for oral exposure of humans to trace amounts via the diet. BPA was weakly estrogenic in screening assays measuring uterine weight/response, although much higher oral doses of BPA were required to elicit a uterotropic response as compared to other routes of administration. The objective of this study was to determine if a route dependency exists in the pharmacokinetics and metabolism of ¹⁴C-labeled BPA following single oral (po), i.p., or s.c. doses of either 10 or 100 mg/kg to Fischer 344 rats. Results indicated a marked route dependency in the pharmacokinetics of BPA. The relative bioavailability of BPA and plasma radioactivity was markedly lower following oral administration as compared to s.c. or i.p. administration. The major fraction of plasma radioactivity following oral dosing was the monoglucuronide conjugate of BPA (68-100% of plasma radioactivity). BPA was the major component in plasma at Cmax following s.c. or i.p. administration exceeded only by BPA-monoglucuronide in females dosed i.p. Up to four addnl. unidentified metabolites were present only in the plasma of animals dosed i.p. or s.c. One of these, found only following i.p. administration, was tentatively identified as the monosulfate conjugate of BPA. The monoglucuronide conjugate was the major urinary metabolite; unchanged BPA was the principal component excreted in feces. These results demonstrated a route dependency of BPA bioavailability in rats, with oral administration resulting in the lowest bioavailability, and offer an explanation for the apparent route differences in estrogenic potency observed for BPA.

Toxicological Sciences published new progress about 267244-08-6. 267244-08-6 belongs to tetrahydropyran, auxiliary class Tetrahydropyran,Chiral,Carboxylic acid,Benzene,Phenol,Alcohol,Ether,, name is (2S,3S,4S,5R,6S)-3,4,5-Trihydroxy-6-(4-(2-(4-hydroxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-2-carboxylic acid, and the molecular formula is C21H24O8, Category: tetrahydropyran.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydropyran,
Tetrahydropyran – an overview | ScienceDirect Topics

Waechter, J. Jr. published the artcileFactors affecting the accuracy of bisphenol A and bisphenol A-monoglucuronide estimates in mammalian tissues and urine samples, Application of (2S,3S,4S,5R,6S)-3,4,5-Trihydroxy-6-(4-(2-(4-hydroxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-2-carboxylic acid, the publication is Toxicology Mechanisms and Methods (2007), 17(1), 13-24, database is CAplus and MEDLINE.

Bisphenol A (BPA) (CAS Number 80-05-7; EINECS Number 201-245-8) is used in the production of plastics having food contact applications. Some biomonitoring studies have reported free BPA in blood or urine of humans. Since complete 1st-pass metabolism of orally administered BPA to BPA-monoglucuronide (BPA-G) occurs in humans, the presence of free BPA in human specimens raises questions as to the origin and/or possible sources of the free BPA. We hypothesized that BPA-G instability during specimen collection and anal. contributes to the presence of free BPA in the biol. samples. Investigation of the in vitro hydrolysis of BPA-G in blood plasma, tissue homogenates, and diluted urine from laboratory rats and in aqueous/organic solutions commonly used for extraction in BPA analyses lent support to the hypothesis of BPA-G instability as a possible source of free BPA determinations in the biol. specimens. Hydrolysis of BPA-G occurred at neutral pH and room temperature in diluted urine and in rat placental or fetal tissue homogenates at room temperature Hydrolysis of BPA-G in aqueous/organic solutions began within minutes at pH 2 and 80°C. BPA-G was degraded to an unidentified compound in a urine/water mixture or when stored in a 25/75 mixture of urine/acetonitrile at pH 9 at either 22 or 80°C. Based upon these experiments, it was concluded that methods demonstrating BPA-G stability or accounting for its instability during anal. are warranted in studies designed to measure free BPA in biol. specimens.

Toxicology Mechanisms and Methods published new progress about 267244-08-6. 267244-08-6 belongs to tetrahydropyran, auxiliary class Tetrahydropyran,Chiral,Carboxylic acid,Benzene,Phenol,Alcohol,Ether,, name is (2S,3S,4S,5R,6S)-3,4,5-Trihydroxy-6-(4-(2-(4-hydroxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-2-carboxylic acid, and the molecular formula is C19H28BNO4, Application of (2S,3S,4S,5R,6S)-3,4,5-Trihydroxy-6-(4-(2-(4-hydroxyphenyl)propan-2-yl)phenoxy)tetrahydro-2H-pyran-2-carboxylic acid.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydropyran,
Tetrahydropyran – an overview | ScienceDirect Topics

Williams, G. M. published the artcilePhenol and phenol derivatives, HPLC of Formula: 69097-99-0, the publication is WHO Food Additives Series (2011), 207-253, database is CAplus.

The Committee evaluated 13 addnl. flavoring agents belonging to the group of phenol and phenol derivatives used as flavoring agents, which was evaluated previously. The addnl. substances included an ester of phenol, two polyphenols, a phenol glucoside, alkyl-, alkenyl- or aryl-substituted phenols or their esters, alkoxyphenols or their esters and phenol derivatives with alkyl side-chains containing a ketone function. Generally, the Committee concluded that these 13 flavoring agents, which are additions to the group of phenol and phenol derivatives evaluated previously, would not give rise to safety concerns at current estimated dietary exposures.

WHO Food Additives Series published new progress about 69097-99-0. 69097-99-0 belongs to tetrahydropyran, auxiliary class Other Aliphatic Heterocyclic,Benzene,Phenol,Ether,Inhibitor, name is 5,7-Dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one, and the molecular formula is C15H14O3, HPLC of Formula: 69097-99-0.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydropyran,
Tetrahydropyran – an overview | ScienceDirect Topics

Kammerer-Pentier, Claire published the artcileDual reactivity of O-α-allenyl esters under palladium(0) catalysis: From carbopalladation/allylic alkylation domino sequence to decarboxylative allenylation, SDS of cas: 27943-46-0, the publication is Journal of Organometallic Chemistry (2012), 53-59, database is CAplus.

In a mechanistically-oriented study, O-α-allenyl esters have been evaluated as potential substrates for Pd-catalyzed carbopalladation/allylic alkylation domino sequences and decarboxylative allenylation reactions. The domino sequence turned out to be feasible only with electron-deficient aryl iodides, thereby showing a narrower potential than that previously observed with the malonamide-based series. The decarboxylative allenylation of O-α-allenyl esters was also tested and turned out to be practicable with β-ketoester-based substrates and using specific basic conditions. Plausible reaction mechanisms are proposed to account for the observed reactivities.

Journal of Organometallic Chemistry published new progress about 27943-46-0. 27943-46-0 belongs to tetrahydropyran, auxiliary class Tetrahydropyran,Alkynyl,Ether, name is 2-((2-Methylbut-3-yn-2-yl)oxy)tetrahydro-2H-pyran, and the molecular formula is C10H16O2, SDS of cas: 27943-46-0.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydropyran,
Tetrahydropyran – an overview | ScienceDirect Topics

Franck-Neumann, M. published the artcileTotal stereospecific synthesis of cis-chrysanthemic methyl ester: the cyclopropenic way, Synthetic Route of 27943-46-0, the publication is Tetrahedron Letters (1980), 21(7), 671-4, database is CAplus.

The title Me ester I (R = R¹ = H) was prepared in 3 steps in 68% yield from Me₂C:CHCCCO₂Me (II). II, prepared (71%) from HOCMe₂CH₂CCH in 2 steps, underwent cycloaddition with Me₂CN:NH at 0° to give 26% pyrazole III (R = CO₂Me, R¹ = CH:CMe₂) and 63% III (R = CH:CMe₂, R¹ = CO₂Me). UV irradiation of the pyrazoles gave the cyclopropene I (RR¹ = bond), which underwent selective cis hydrogenation with KO₂CN:NCO₂K in AcOH to give 90% Me ester I (R = R¹ = H).

Tetrahedron Letters published new progress about 27943-46-0. 27943-46-0 belongs to tetrahydropyran, auxiliary class Tetrahydropyran,Alkynyl,Ether, name is 2-((2-Methylbut-3-yn-2-yl)oxy)tetrahydro-2H-pyran, and the molecular formula is C10H16O2, Synthetic Route of 27943-46-0.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydropyran,
Tetrahydropyran – an overview | ScienceDirect Topics

Yu, Bo published the artcileNetwork pharmacology-based identification for therapeutic mechanisms of Dangguikushen pill in acne vulgaris, Application In Synthesis of 69097-99-0, the publication is Dermatologic Therapy (2020), 33(6), e14061, database is CAplus and MEDLINE.

The Dangguikushen (DGKS) pill is a proprietary traditional Chinese medicine that has shown superior efficacy in the treatment of acne vulgaris for many years. A network pharmacol.-based anal. was performed to explore the potential anti-acne compounds, core therapeutic targets, and the main pathways, involved in the DGKS pill bioactivity. The matching results between the predicted targets of the DGKS pill and the well-known targets of acne vulgaris were collected, followed by network establishment using protein-protein interaction (PPI) data. Cytoscape was utilized to analyze the network and screen the core targets. Furthermore, the Database for Annotation, Visualization and Integrated Discovery (DAVID), and ClueGO were used for the enrichment anal. of the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathways and Gene Ontol. biol. processes (GO-BP). Finally, the “compound-target-pathway” network was constructed. This approach identified 19 active compounds, 46 therapeutic targets, and 12 core therapeutic targets of the DGKS pill. The biol. processes were primarily related to reactive oxygen species (ROS) metabolic process, gland morphogenesis, and female gonad development. The DGKS pill was significantly associated with eight pathways including the PI3K-Akt, TNF, NF-kappa B, and p53 signaling pathways. DGKS pill might have a synergistic effect on the inhibition of excessive sebaceous lipogenesis and sebocyte differentiation, and likewise, anti-inflammatory effects via the different signaling pathways (PI3K-Akt, TNF, NF-kappa B, and p53).

Dermatologic Therapy published new progress about 69097-99-0. 69097-99-0 belongs to tetrahydropyran, auxiliary class Other Aliphatic Heterocyclic,Benzene,Phenol,Ether,Inhibitor, name is 5,7-Dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one, and the molecular formula is C17H37NO3, Application In Synthesis of 69097-99-0.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydropyran,
Tetrahydropyran – an overview | ScienceDirect Topics

Ye, Xian-wen published the artcileStudy on the mechanism of treating COVID-19 with Shenqi Wan based on network pharmacology, Application of 5,7-Dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one, the publication is Drug Development and Industrial Pharmacy (2021), 47(8), 1279-1289, database is CAplus and MEDLINE.

Through the method of network pharmacol., the active components and targets of Shenqi Wan (SQW) were excavated, the relationship with novel Coronavirus pneumonia (COVID-19) was discussed, and the possible mechanism of SQW in the treatment of COVID-19 was revealed from the aspects of multicomponents, multitargets, and multipathways. Firstly, the active components of SQW were screened from traditional Chinese medicine systems pharmacol. database and anal. platform and the 2020 edition of Chinese Pharmacopeia, and the related targets of the components were obtained. Then the disease targets related to COVID-19 were screened from GeneCards and Online Mendelian Inheritance in Man. Venny was used to map the relationship between component-target and disease-target, and String was used to analyze the interaction of common targets. The network was constructed and analyzed by Cytoscape, the function of Gene ontol. (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) genes was enriched by Metascape, and the mol. docking was verified by CB-Dock. Finally, 45 active components of SQW were obtained, and 72 potential targets were related to COVID-19, angiotensin-converting enzyme 2 (ACE2), interleukin (IL)-6, nitric oxide synthase (NOS3) and, C-reactive protein (CRP),may be the key targets. GO enrichment of 1715 projects, such as lipopolysaccharide stress response, active oxygen metabolism, pos. regulation of cell migration, and other GO enrichment. About 136 KEGG pathways, tumor necrosis factor signaling pathway, IL-17 signaling pathway, hypoxia-inducible factor 1-α signaling pathway were obtained. Mol. docking showed that kaempferol, quercetin, luteolin, astragaloside, calyx isoflavone glucoside, matrine, and other COVID-19-related targets such as ACE2, chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), prostaglandin-endoperoxide synthase 2 (PTGS2) have good binding ability. According to the above results, it is suggested that SQW may play a role in the treatment of COVID-19 by directly or indirectly combining kaempferol, quercetin, and luteolin with ACE2, 3CLpro, PLpro, and PTGS2 to regulate multiple biol. functions and signaling pathways.

Drug Development and Industrial Pharmacy published new progress about 69097-99-0. 69097-99-0 belongs to tetrahydropyran, auxiliary class Other Aliphatic Heterocyclic,Benzene,Phenol,Ether,Inhibitor, name is 5,7-Dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one, and the molecular formula is C14H14N2O2, Application of 5,7-Dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydropyran,
Tetrahydropyran – an overview | ScienceDirect Topics