Author: tianli

Rueeger, Heinrich published the artcileDiscovery of Cyclic Sulfone Hydroxyethylamines as Potent and Selective β-Site APP-Cleaving Enzyme 1 (BACE1) Inhibitors: Structure-Based Design and in Vivo Reduction of Amyloid β-Peptides, Related Products of alcohols-buliding-blocks, the publication is Journal of Medicinal Chemistry (2012), 55(7), 3364-3386, database is CAplus and MEDLINE.

Structure-based design of a series of cyclic hydroxyethylamine BACE1 inhibitors allowed the rational incorporation of prime- and nonprime-side fragments to a central core template without any amide functionality. The core scaffold selection and the structure-activity relationship development were supported by mol. modeling studies and by x-ray anal. of BACE1 complexes with various ligands to expedite the optimization of the series. The direct extension from P1-aryl- and heteroaryl moieties into the S3 binding pocket allowed the enhancement of potency and selectivity over cathepsin D. Restraining the design and synthesis of compounds to a physicochem. property space consistent with central nervous system drugs led to inhibitors with improved blood-brain barrier permeability. Guided by structure-based optimization, highly potent compounds were obtained, such as I, with enzymic and cellular IC₅₀ values of 2 and 50 nM, resp., and with >200-fold selectivity over cathepsin D. Pharmacodynamic studies in APP51/16 transgenic mice at oral doses of 180 μmol/kg demonstrated significant reduction of brain Aβ levels.

Journal of Medicinal Chemistry 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 C3H5F3O, Related Products of alcohols-buliding-blocks.

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

Siewert, Riko published the artcileNon-covalent interactions in molecular systems: thermodynamic evaluation of the hydrogen bond strength in aminoalcohols, Recommanded Product: 2-Aminobutan-1-ol, the publication is Physical Chemistry Chemical Physics (2021), 23(44), 25226-25238, database is CAplus and MEDLINE.

In mols. with two functional groups that form hydrogen bonds, the structure-property relationship can depend significantly on the strength of intra-mol. hydrogen bonding. This bonding can cause a substantial conformational change that is accompanied by a frequency shift in the IR spectrum, which provides the basis for exptl. studies. Despite its great importance in biol. systems, the available literature data for the strength of this bonding are scarce and not in agreement. In this work, we present the results of four thermodn. methods for the determination of the strength of intramol. hydrogen bonds. Comprehensive thermochem. anal. of 1-amino-2-alcs. and 2-amino-1-alcs. was performed with Fourier-transform IR spectroscopy, high-level G4 quantum-chem. calculations, the homomorph scheme with enthalpies of vaporization and a group contribution method. With the combination of these four thermodn. methods, the strength of intramol. hydrogen bonding in 1,2-aminoalcs. and 2,1-aminoalcs. was evaluated quant. The results were correlated with NBO parameters to find an explanation for the different strengths of intramol. hydrogen bonds in total charge transfer and second order stabilization energies.

Physical Chemistry Chemical Physics published new progress about 96-20-8. 96-20-8 belongs to alcohols-buliding-blocks, auxiliary class Amine,Aliphatic hydrocarbon chain,Alcohol, name is 2-Aminobutan-1-ol, and the molecular formula is C7H14N4, Recommanded Product: 2-Aminobutan-1-ol.

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

Kluczyk, Alicja published the artcileArgireline: Needle-Free Botox as Analytical Challenge, Computed Properties of 70445-33-9, the publication is Chemistry & Biodiversity (2021), 18(3), e2000992, database is CAplus and MEDLINE.

Argireline-containing cosmetics attract public interest due to their confirmed reduction of facial wrinkles. Argireline is a peptide that works by inhibiting the release of neurotransmitters in the neuromuscular junction, producing a botox-like effect. Therefore, it is used as a safe needle-free alternative to botox treatment. In this work we investigated the presence of Argireline in cosmetic creams and sera by application of reversed phase liquid chromatog. and tandem mass spectrometry (RP-HPLC/MS and MS/MS). The anal. revealed the presence of argireline and its oxidized form in several different cosmetics. The methionine residue in Argireline sequence was indicated as oxidation point according to neutral loss MS studies. The developed sample preparation strategy minimizes and monitors methionine oxidation, bringing to our attention the question of impact of ingredients on the stability of cosmetic product.

Chemistry & Biodiversity published new progress about 70445-33-9. 70445-33-9 belongs to alcohols-buliding-blocks, auxiliary class Aliphatic Chain, name is 3-((2-Ethylhexyl)oxy)propane-1,2-diol, and the molecular formula is C11H24O3, Computed Properties of 70445-33-9.

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

Caliskan, Burcu published the artcilePyrazol-3-propanoic acid derivatives as novel inhibitors of leukotriene biosynthesis in human neutrophils, Application of 4-(1H-Pyrrol-1-yl)phenol, the publication is European Journal of Medicinal Chemistry (2011), 46(10), 5021-5033, database is CAplus and MEDLINE.

Thirty-six title compounds were synthesized and led to potent inhibition of leukotriene (LT) biosynthesis in activated human neutrophils. Some examples showed IC₅₀ values in the range of 1.6-3.5 μM. Moreover, several compounds showed a substantial inhibition of platelet COX-1 activity with IC₅₀ of 2.5, 0.041, 0.3, 0.9 and 0.014 μM, resp., leading up to dual acting inhibitors. On the basis of their high potency in cellular environment, these straightforward pyrazole-3-propanoic acid derivatives may possess potential in the design of more potent compounds for intervention with inflammatory and allergic diseases.

European Journal of Medicinal Chemistry published new progress about 23351-09-9. 23351-09-9 belongs to alcohols-buliding-blocks, auxiliary class Pyrrole,Benzene,Alcohol, name is 4-(1H-Pyrrol-1-yl)phenol, and the molecular formula is C10H9NO, Application of 4-(1H-Pyrrol-1-yl)phenol.

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

Shareef, Afzaal M. published the artcileComparison of RNA synthesis initiation properties of non-segmented negative strand RNA virus polymerases, SDS of cas: 122-20-3, the publication is PLoS Pathogens (2021), 17(12), e1010151, database is CAplus and MEDLINE.

It is generally thought that the promoters of non-segmented, neg. strand RNA viruses (nsNSVs) direct the polymerase to initiate RNA synthesis exclusively opposite the 3′ terminal nucleotide of the genome RNA by a de novo (primer independent) initiation mechanism. However, recent studies have revealed that there is diversity between different nsNSVs with pneumovirus promoters directing the polymerase to initiate at positions 1 and 3 of the genome, and ebolavirus polymerases being able to initiate at position 2 on the template. Studies with other RNA viruses have shown that polymerases that engage in de novo initiation opposite position 1 typically have structural features to stabilize the initiation complex and ensure efficient and accurate initiation. This raised the question of whether different nsNSV polymerases have evolved fundamentally different structural properties to facilitate initiation at different sites on their promoters. Here we examined the functional properties of polymerases of respiratory syncytial virus (RSV), a pneumovirus, human parainfluenza virus type 3 (PIV-3), a paramyxovirus, and Marburg virus (MARV), a filovirus, both on their cognate promoters and on promoters of other viruses. We found that in contrast to the RSV polymerase, which initiated at positions 1 and 3 of its promoter, the PIV-3 and MARV polymerases initiated exclusively at position 1 on their cognate promoters. However, all three polymerases could recognize and initiate from heterologous promoters, with the promoter sequence playing a key role in determining initiation site selection. In addition to examining de novo initiation, we also compared the ability of the RSV and PIV-3 polymerases to engage in back-priming, an activity in which the promoter template is folded into a secondary structure and nucleotides are added to the template 3′ end. This anal. showed that whereas the RSV polymerase was promiscuous in back-priming activity, the PIV-3 polymerase generated barely detectable levels of back-primed product, irresp. of promoter template sequence. Overall, this study shows that the polymerases from these three nsNSV families are fundamentally similar in their initiation properties, but have differences in their abilities to engage in back-priming.

PLoS Pathogens published new progress about 122-20-3. 122-20-3 belongs to alcohols-buliding-blocks, auxiliary class Organic Pigment, name is Triisopropanolamine, and the molecular formula is C4H10BBrO2, SDS of cas: 122-20-3.

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

Zhang, Tao published the artcileA directive Ni catalyst overrides conventional site selectivity in pyridine C-H alkenylation, Computed Properties of 20880-92-6, the publication is Nature Chemistry (2021), 13(12), 1207-1213, database is CAplus and MEDLINE.

Herein, application of bifunctional N-heterocyclic carbene-ligated Ni-Al catalyst in C3-H alkenylation of pyridines was described. This method overrode the intrinsic C2 and/or C4 selectivity, and provided a series of C3-alkenylated pyridines such as I in 43-99% yields and up to 98:2 C3 selectivity. This method not only allowed a variety of pyridine and heteroarene substrates to be used as the limiting reagent, but was also effective for the late-stage C3 alkenylation of diverse complex pyridine motifs in bioactive mols.

Nature 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 C25H29N9O3, Computed Properties of 20880-92-6.

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

Velu, Sadanandan E. published the artcileTethered Dimer Inhibitors of NAD Synthetase: Parallel Synthesis of an Aryl-Substituted SAR Library, Recommanded Product: 3-Morpholinophenol, the publication is Journal of Combinatorial Chemistry (2005), 7(6), 898-904, database is CAplus and MEDLINE.

The authors previously reported that tethered dimers containing indoles on one end and a permanent pos. charge on the other, using a 6-9 carbon polymethylene tether, provided NAD synthetase inhibitors with impressive antibacterial activities against Gram-positives. Here, the authors report that the Ph ring is a good substitute for indole, and the authors utilize solution-phase parallel synthesis to explore structure-activity relationships for substituents on that ring. General conclusions are that nonpolar substituents are more effective than polar ones and that different positional isomers often have very different enzyme inhibition activities. This latter observation reveals that enzyme activity is sensitive to minor structural changes and suggests that nonspecific detergent actions are not important for the observed effects.

Journal of Combinatorial Chemistry published new progress about 27292-49-5. 27292-49-5 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Benzene,Phenol, name is 3-Morpholinophenol, and the molecular formula is C7H6Cl2, Recommanded Product: 3-Morpholinophenol.

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

Song, Xiao-xia published the artcileComparison of the preventive and therapeutic effects of ergometrine maleate, carbetocin and carboprost tromethamine on postpartum hemorrhage caused by uterine asthenia, Application In Synthesis of 58551-69-2, the publication is Guangdong Yixue (2017), 38(18), 2850-2852, 2855, database is CAplus.

This paper discusses the safety and effectiveness of ergometrine maleate, carbetocin and carboprost aminobutyric triol in the prevention and treatment of postpartum hemorrhage caused by uterine asthenia during vaginal delivery. These three drugs are safe and effective when postpartum uterine atony occurs in patients with vaginal delivery. Carbetocin can be used as the first choice for oxytocin combination, but due to their different clin. characteristics, the drug selection should take into account the principle of individualization.

Guangdong Yixue published new progress about 58551-69-2. 58551-69-2 belongs to alcohols-buliding-blocks, auxiliary class Chiral,Alkenyl,Amine,Aliphatic cyclic hydrocarbon,Ester,Alcohol,Inhibitor,, name is 2-Amino-2-(hydroxymethyl)propane-1,3-diol (Z)-7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((S,E)-3-hydroxy-3-methyloct-1-en-1-yl)cyclopentyl)hept-5-enoic acid, and the molecular formula is C12H9NO, Application In Synthesis of 58551-69-2.

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

Lin, Jian published the artcileDiscovery and Optimization of Quinolinone Derivatives as Potent, Selective, and Orally Bioavailable Mutant Isocitrate Dehydrogenase 1 (mIDH1) Inhibitors, HPLC of Formula: 622-40-2, the publication is Journal of Medicinal Chemistry (2019), 62(14), 6575-6596, database is CAplus and MEDLINE.

Mutations at the arginine residue (R132) in isocitrate dehydrogenase 1 (IDH1) are frequently identified in various human cancers. Inhibition of mutant IDH1 (mIDH1) with small mols. has been clin. validated as a promising therapeutic treatment for acute myeloid leukemia and multiple solid tumors. Herein, we report the discovery and optimization of a series of quinolinones to provide potent and orally bioavailable mIDH1 inhibitors with selectivity over wild-type IDH1. The X-ray structure of an early lead 24 in complex with mIDH1-R132H shows that the inhibitor unexpectedly binds to an allosteric site. Efforts to improve the in vitro and in vivo absorption, distribution, metabolism, and excretion (ADME) properties of 24 yielded a preclin. candidate 63. The detailed preclin. ADME and pharmacol. studies of 63 support further development of quinolinone-based mIDH1 inhibitors as therapeutic agents in human trials.

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 C6H13NO2, HPLC of Formula: 622-40-2.

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

Li, Xin published the artcileSmall molecule-mediated upregulation of CCR7 ameliorates murine experimental autoimmune encephalomyelitis by accelerating T-cell homing, Formula: C9H21NO3, the publication is International Immunopharmacology (2017), 33-41, database is CAplus and MEDLINE.

Impairing the infiltration of immune cells into the CNS is a promising target for suppressing the development of multiple sclerosis (MS) and its animal model exptl. autoimmune encephalomyelitis (EAE). Here, we found that oral administration of a synthetic small mol. compound Fc24 showed potential preventive effects on the development of EAE, including the reduction in EAE severity and a delay in the onset of the disease. Fc24 facilitated the accumulation of both CD4⁺ and CD8⁺ T cells within spleen and lymph nodes, while having no effect on MOG-specific T cell responses. Furthermore, CCR7 expression was upregulated by Fc24 on activated T cells in vivo and in vitro, accompanied by ERK activation in the treated T cells in response to CCL19. These findings demonstrate that small mol.-mediated CCR7 upregulation might ameliorate EAE by facilitating T cell homing into and within lymphoid organs, and that Fc24 may be a potential candidate for modifying the development of EAE.

International Immunopharmacology published new progress about 122-20-3. 122-20-3 belongs to alcohols-buliding-blocks, auxiliary class Organic Pigment, name is Triisopropanolamine, and the molecular formula is C9H21NO3, Formula: C9H21NO3.

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