Month: December 2022

Gerke, Christoph published the artcileDirect glucosone-based synthesis and HILIC-ESI-MS/MS characterization of N-terminal fructosylated valine and valylhistidine for validation of enzymatic HbA_1c assays in the diagnosis of diabetes mellitus, Formula: C12H20O6, the publication is Analytical and Bioanalytical Chemistry (2019), 411(30), 7967-7979, database is CAplus and MEDLINE.

Naturally occurring fructosamines are of high clin. significance due to their potential use in diabetes mellitus monitoring (quantification of fructosylated Hb, HbA_1c) or for the study of their reactivity in consecutive reactions and harmfulness towards the organism. Here the authors report the specific synthesis of the fructosylated dipeptide L-valyl-L-histidine (Fru-Val-His) and fructosylated L-valine (Fru-Val). Both are basic tools for the development and validation of enzymic HbA_1c assays. The two fructosamine derivatives were synthesized via a protected glucosone intermediate which was coupled to the primary amine of Val or Val-His, performing a reductive amination reaction. Overall yields starting from fructose were 36% and 34% for Fru-Val and Fru-Val-His, resp. Both compounds were achieved in purities and > 90%. A HILIC-ESI-MS/MS method was developed for routine anal. of the synthesized fructosamines, including starting materials and intermediates. The presented method provides a well-defined and efficient synthesis protocol with purification steps and characterization of the desired products. The functionality of the fructosylated dipeptide has been thoroughly tested in an enzymic HbA_1c assay, showing its concentration-dependent oxidative degradation by fructosyl-peptide oxidases (FPOX).

Analytical and Bioanalytical Chemistry published new progress about 20880-92-6. 20880-92-6 belongs to alcohols-buliding-blocks, auxiliary class Other Aliphatic Heterocyclic,Chiral,Alcohol, name is ((3aS,5aR,8aR,8bS)-2,2,7,7-Tetramethyltetrahydro-3aH-bis([1,3]dioxolo)[4,5-b:4′,5′-d]pyran-3a-yl)methanol, and the molecular formula is C12H20O6, Formula: C12H20O6.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Spinaci, Andrea published the artcileA3 Adenosine Receptor Antagonists with Nucleoside Structures and Their Anticancer Activity, Category: alcohols-buliding-blocks, the publication is Pharmaceuticals (2022), 15(2), 164, database is CAplus and MEDLINE.

The overexpression of the A3 adenosine receptor (AR) in a number of cancer cell types makes it an attractive target for tumor diagnosis and therapy. Hence, in the search for new A3AR ligands, a series of novel 2,N⁶-disubstituted adenosines (Ados) I (R¹ = (CH₂)₂C₆H₅, (CH₂)₂CH(C₆H₅)₂; R² = (CH₂)₃CH₃, C₆H₅) was synthesized and tested in radioligand binding and functional assays at ARs. Derivatives bearing a 2-phenethylamino group in the N⁶-position were found to exert higher A3AR affinity and selectivity than the corresponding N⁶-(2,2-diphenylethyl) analogs. 2-Chloro-N⁶-phenylethylAdo was found to be a potent full A3AR agonist with a Ki of 0.024 nM and an EC₅₀ of 14 nM, in a cAMP accumulation assay. Unlike 2-chloro-N⁶-phenylethylAdo, the other ligands behaved as A3AR antagonists, which concentration-dependently reduced cell growth and exerted cytostatic activity on the prostate cancer cell line PC3, showing comparable and even more pronounced effects with respect to the ones elicited by the reference full agonist Cl-IB-MECA. In particular, the N⁶-(2,2-diphenylethyl)-2-phenylethynylAdo (GI₅₀ = 14μM, TGI = 29μM, and LC₅₀ = 59μM) showed the highest activity proving to be a potential antitumor agent. The cytostatic effect of both A3AR agonist (Cl-IB-MECA) and antagonists (other newly synthesized compounds) confirm previous observations according to which, in addition to the involvement of A3ARs, other cellular mechanisms are responsible for the anticancer effects of these ligands.

Pharmaceuticals published new progress about 4410-99-5. 4410-99-5 belongs to alcohols-buliding-blocks, auxiliary class Thiol,Benzene, name is 2-Phenylethanethiol, and the molecular formula is C8H15ClN2, Category: alcohols-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Smolinski, Michael P. published the artcileDiscovery of Novel Dual Mechanism of Action Src Signaling and Tubulin Polymerization Inhibitors (KX2-391 and KX2-361), Formula: C6H13NO2, the publication is Journal of Medicinal Chemistry (2018), 61(11), 4704-4719, database is CAplus and MEDLINE.

The discovery of potent, peptide site directed, tyrosine kinase inhibitors has remained an elusive goal. Herein we describe the discovery of two such clin. candidates that inhibit the tyrosine kinase Src. Compound 1 is a phase 3 clin. trial candidate that is likely to provide a first in class topical treatment for actinic keratosis (AK) with good efficacy and dramatically less toxicity compared to existing standard therapy. Compound 2 is a phase 1 clin. trial candidate that is likely to provide a first in class treatment of malignant glioblastoma and induces 30% long-term complete tumor remission in animal models. The discovery strategy for these compounds iteratively utilized mol. modeling, along with the synthesis and testing of increasingly elaborated proof of concept compounds, until the final clin. candidates were arrived at. This was followed with mechanism of action (MOA) studies that revealed tubulin polymerization inhibition as the second MOA.

Journal of Medicinal Chemistry published new progress about 622-40-2. 622-40-2 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Alcohol, name is 2-Morpholinoethanol, and the molecular formula is C22H12F6O6S2, Formula: C6H13NO2.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Vysotsky, Yu. B. published the artcileQuantum Chemical Semiempirical Approach to the Structural and Thermodynamic Characteristics of Fluoroalkanols at the Air/Water Interface, Recommanded Product: 3,3,3-Trifluoropropan-1-ol, the publication is Journal of Physical Chemistry B (2005), 109(1), 454-462, database is CAplus and MEDLINE.

In the framework of quantum chem. PM3 approximation, the geometrical structure and thermodn. functions characteristics of the formation of monomers (n = 1-14, 34), dimers (n = 1-14, 34), and trimers and tetramers (n = 1-8) of fluoroalkanols with the composition C_nF_2n+1CH₂CH₂OH are calculated It is shown that, in contrast to the fatty alcs., which have a flat zigzag structure, the fluoroalkanol monomers are helical with an average backbone torsion angle equal to 162°. For the min.-energy structure of dimers, the self-organization of the mols. in a dimer was observed; that leads to an opposite alternation of the torsion angles corresponding to the matching atoms in the two mols. that form the dimer. This results in the fact that the most stable conformation of the dimer is the double helix. The lead (39.5 Å) and diameter (7.3 Å) of the double helix are determined from the calculations of C₃₄F₆₉CH₂CH₂OH dimers. Enthalpy, entropy, and Gibbs energy of the clusterization are shown to be linearly dependent on the length of the fluorinated chain. From the anal. of these thermodn. quantities, it is concluded that dimerization of fluoroalkanols at the air/water interface takes place if the hydrocarbon link number exceeds 6, whereas for ordinary alcs. this characteristic number is 11. These calculated values agree with exptl. data. The additive scheme for the evaluation of the clusterization free energies for arbitrary clusters is developed and applied to obtain the estimate of the Gibbs clusterization energy for infinitely large clusters.

Journal of Physical Chemistry B published new progress about 2240-88-2. 2240-88-2 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Aliphatic hydrocarbon chain,Alcohol, name is 3,3,3-Trifluoropropan-1-ol, and the molecular formula is C11H8O3, Recommanded Product: 3,3,3-Trifluoropropan-1-ol.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Chapman, Eli published the artcileMechanistic studies of β-arylsulfotransferase IV, Quality Control of 120103-18-6, the publication is Proceedings of the National Academy of Sciences of the United States of America (2003), 100(3), 910-915, database is CAplus and MEDLINE.

Sulfotransferases are an important class of enzymes that catalyze the transfer of a sulfuryl group to a hydroxyl or amine moiety on various mols. including small-mol. drugs, steroids, hormones, carbohydrates, and proteins. They have been implicated in a number of disease states but remain poorly understood, complicating the design of specific, small-mol. inhibitors. A linear free-energy anal. in both the forward and reverse directions indicates that the transfer of a sulfuryl group to an aryl hydroxyl group catalyzed by β-arylsulfotransferase IV likely proceeds by a dissociative (sulfotrioxide-like) mechanism. Values for the Bronsted coefficients (β_nuc and β_lg) are +0.33 and -0.45, giving Leffler α values of 0.19 and 0.61 for the forward and reverse reactions, resp.

Proceedings of the National Academy of Sciences of the United States of America published new progress about 120103-18-6. 120103-18-6 belongs to alcohols-buliding-blocks, auxiliary class Fluoride,Nitro Compound,Benzene,Phenol, name is 2,5-Difluoro-4-nitrophenol, and the molecular formula is C6H3F2NO3, Quality Control of 120103-18-6.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Kennedy, Andrew J. published the artcileSynthesis and antimicrobial evaluation of amixicile-based inhibitors of the pyruvate-ferredoxin oxidoreductases of anaerobic bacteria and Epsilonproteobacteria, Quality Control of 328-90-5, the publication is Antimicrobial Agents and Chemotherapy (2016), 60(7), 3980-3987, database is CAplus and MEDLINE.

Synthesis of the amixicile scaffolds I [R = CH₂NH₃, (CH₂)₃NH₃, 4-piperidinyl, etc.; R¹ = H, F; R² = H, Me, F, Cl, CF₃; R³ = H, Me, OMe, F, Cl, CN, CF₃] and study of their direct pyruvate-ferredoxin oxidoreductases (PFOR) inhibition assays, and MIC tests against Clostridium difficile, Campylobacter jejuni, and Helicobacter pylori guided by docking simulations was interrogated. Docking simulations revealed that the nitro group present in nitazoxanide interacts with the protonated N4′-aminopyrimidine of thiamine pyrophosphate. The ortho-propylamine on the benzene ring formed an electrostatic interaction with an aspartic acid moiety (B456) of PFOR that correlated with improved PFOR-inhibitory activity and potency by MIC tests. Aryl substitution with electron-withdrawing groups and substitutions of the propylamine with other alkyl amines or nitrogen-containing heterocycles both improved PFOR inhibition and, in many cases, biol. activity against C. difficile. Docking simulation results correlated well with mechanistic enzymol. and NMR studies that show members of this class of antimicrobials to be specific inhibitors of vitamin B₁ function by proton abstraction, which is both novel and likely to limit mutation-based drug resistance.

Antimicrobial Agents and Chemotherapy published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Quality Control of 328-90-5.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Mariella, R. P. published the artcileNovel SNl displacement. Reaction of tertiary amines with acetic anhydride, Computed Properties of 101-98-4, the publication is Canadian Journal of Chemistry (1971), 49(20), 3348-51, database is CAplus.

The action of Ac2O on tertiary amines at reflux may cause the displacement of one of the R groups from the amine. The groups which are displaced are benzyl, tert-Bu, benzhydryl, trityl, and cinnamyl; the groups which are not displaced are Me, Et, Bu, Ph, α-naphthyl, iso-Pr, allyl, and propargyl, An SN 1 mechanism with special steric requirements is consistent with the results.

Canadian Journal of Chemistry published new progress about 101-98-4. 101-98-4 belongs to alcohols-buliding-blocks, auxiliary class Amine,Benzene,Alcohol, name is 2-(Benzyl(methyl)amino)ethanol, and the molecular formula is C10H15NO, Computed Properties of 101-98-4.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Sawyer, Dennis E. published the artcileThe use of an in vitro sperm activation assay to detect chemically induced damage of human sperm nuclei, Name: Bis(2,5-dioxopyrrolidin-1-yl) O,O’-ethane-1,2-diyl disuccinate, the publication is Reproductive Toxicology (1995), 9(4), 351-7, database is CAplus and MEDLINE.

We report that human sperm chem. damaged in vitro by treatment with a reversible crosslinker, ethylene glycol bis(sulfosuccinimidylsuccinate; SEGS), display abnormal chromatin decondensation when analyzed in the human sperm activation assay (HSAA). Less than 20% of SEGS-treated sperm fully decondensed, vs. 97% of control sperm. Chem. reversal of the crosslinks by treatment with 5 μM hydroxylamine restored full decondensation in 76% of treated sperm. These results demonstrate that chem. damaged sperm respond abnormally in the HSAA, and that chem. damage to sperm nuclei can be detected using the HSAA. Thus, there is potential for the HSAA to be used to detect chem. alterations of sperm nuclei from men exposed to environmental toxicants.

Reproductive Toxicology published new progress about 70539-42-3. 70539-42-3 belongs to alcohols-buliding-blocks, auxiliary class pyrrolidine,Ester,Amide,Inhibitor,Inhibitor, name is Bis(2,5-dioxopyrrolidin-1-yl) O,O’-ethane-1,2-diyl disuccinate, and the molecular formula is C18H20N2O12, Name: Bis(2,5-dioxopyrrolidin-1-yl) O,O’-ethane-1,2-diyl disuccinate.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Newman, Melvin S. published the artcilegem-Dialkyl effect in medicinal agents, Quality Control of 39943-41-4, the publication is Journal of Medicinal Chemistry (1972), 15(10), 1003-6, database is CAplus and MEDLINE.

Modification of various drugs (cholinergic agonists and antagonists, ganglionic blockers, antihistamines, local anesthetics) containing a dialkylaminoethoxy group R2N(CH2)2O by insertion of a gem-dialkylmethylene group, forming R2NCH2CR12CH2O, did not produce progressive changes in activity related to the nature of the gem-dialkyl substituents. The gem-dialkyl substituents used were Me, Et, and cycloalkyl (cyclopropyl to cyclohexyl). Varying these substituents altered the distance between N and O atoms in the alkanolamine group, which was evidently not an important parameter for activity.

Journal of Medicinal Chemistry published new progress about 39943-41-4. 39943-41-4 belongs to alcohols-buliding-blocks, auxiliary class Cyclopropanes, name is (1-((Dimethylamino)methyl)cyclopropyl)methanol, and the molecular formula is C7H15NO, Quality Control of 39943-41-4.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

De Gasparo, Raoul published the artcileBiological Evaluation and X-ray Co-crystal Structures of Cyclohexylpyrrolidine Ligands for Trypanothione Reductase, an Enzyme from the Redox Metabolism of Trypanosoma, Safety of 2-Morpholinoethanol, the publication is ChemMedChem (2018), 13(9), 957-967, database is CAplus and MEDLINE.

The tropical diseases human African trypanosomiasis, Chagas disease, and the various forms of leishmaniasis are caused by parasites of the family of trypanosomatids. These protozoa possess a unique redox metabolism based on trypanothione and trypanothione reductase (TR), making TR a promising drug target. We report the optimization of properties and potency of cyclohexylpyrrolidine inhibitors of TR by structure-based design. The best inhibitors were freely soluble and showed competitive inhibition constants (K_i) against Trypanosoma (T.) brucei TR and T. cruzi TR and in vitro activities (half-maximal inhibitory concentration, IC₅₀) against these parasites in the low micromolar range, with high selectivity against human glutathione reductase. X-ray co-crystal structures confirmed the binding of the ligands to the hydrophobic wall of the “mepacrine binding site” with the new, solubility-providing vectors oriented toward the surface of the large active site.

ChemMedChem published new progress about 622-40-2. 622-40-2 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Alcohol, name is 2-Morpholinoethanol, and the molecular formula is C6H13NO2, Safety of 2-Morpholinoethanol.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts