Category: alcohols-buliding-blocks

Klein, Victoria G. published the artcileAmide-to-Ester Substitution as a Strategy for Optimizing PROTAC Permeability and Cellular Activity, Application of Pentane-1,5-diol, the publication is Journal of Medicinal Chemistry (2021), 64(24), 18082-18101, database is CAplus and MEDLINE.

Criteria for predicting the druglike properties of “beyond Rule of 5” Proteolysis Targeting Chimeras (PROTAC) degraders are underdeveloped. PROTAC components are often combined via amide couplings due to their reliability. Amides, however, can give rise to poor absorption, distribution, metabolism, and excretion (ADME) properties. We hypothesized that a bioisosteric amide-to-ester substitution could lead to improvements in both physicochem. properties and bioactivity. Using model compounds, bearing either amides or esters, we identify parameters for optimal lipophilicity and permeability. We applied these learnings to design a set of novel amide-to-ester-substituted, VHL-based BET degraders with the goal to increase permeability. Our ester PROTACs retained intracellular stability, were overall more potent degraders than their amide counterparts, and showed an earlier onset of the hook effect. These enhancements were driven by greater cell permeability rather than improvements in ternary complex formation. This largely unexplored amide-to-ester substitution provides a simple strategy to enhance PROTAC permeability and bioactivity and may prove beneficial to other beyond Ro5 mols.

Journal of Medicinal Chemistry published new progress about 111-29-5. 111-29-5 belongs to alcohols-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Alcohol,Ploymers, name is Pentane-1,5-diol, and the molecular formula is C5H12O2, Application of Pentane-1,5-diol.

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

Peiro Cadahia, Jorge published the artcileSynthesis and Evaluation of Hydrogen Peroxide Sensitive Prodrugs of Methotrexate and Aminopterin for the Treatment of Rheumatoid Arthritis, COA of Formula: C14H21BO3, the publication is Journal of Medicinal Chemistry (2018), 61(8), 3503-3515, database is CAplus and MEDLINE.

A series of novel hydrogen peroxide sensitive prodrugs I (11–13; R = H, Me, F) of methotrexate (MTX) and aminopterin (AMT) were synthesized and evaluated for therapeutic efficacy in mice with collagen induced arthritis (CIA) as a model of chronic rheumatoid arthritis (RA). The prodrug strategy selected is based on ROS-labile 4-methylphenylboronic acid promoieties linked to the drugs via a carbamate linkage or a direct C-N bond. Activation under pathophysiol. concentrations of H₂O₂ proved to be effective, and prodrug candidates were selected in agreement with relevant in vitro physicochem. and pharmacokinetic assays. Selected candidates showed moderate to good solubility, high chem. and enzymic stability, and therapeutic efficacy comparable to the parent drugs in the CIA model. Importantly, the prodrugs displayed the expected safer toxicity profile and increased therapeutic window compared to MTX and AMT while maintaining a comparable therapeutic efficacy, which is highly encouraging for future use in RA patients.

Journal of Medicinal Chemistry published new progress about 1370732-71-0. 1370732-71-0 belongs to alcohols-buliding-blocks, auxiliary class Boronic acid and ester, name is (3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanol, and the molecular formula is C14H21BO3, COA of Formula: C14H21BO3.

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

Gros, Philippe published the artcileFirst activation of sodium amide by polymer-supported alkoxides and amino-alkoxides, HPLC of Formula: 101-98-4, the publication is Reactive & Functional Polymers (2000), 43(1,2), 117-122, database is CAplus.

Polystyrene-supported alkoxides and amino-alkoxides are shown to act as efficient and reusable activating agents of sodium amide. This constitutes an unprecedented example of heterogeneous activation in sodium carbanion chem.

Reactive & Functional Polymers 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, HPLC of Formula: 101-98-4.

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

Guan, Renpeng published the artcileDecarboxylative oxygenation of carboxylic acids with O₂via a non-heme manganese catalyst, HPLC of Formula: 90-64-2, the publication is Green Chemistry (2022), 24(7), 2946-2952, database is CAplus.

Decarboxylative oxygenation of carboxylic acids using a non-heme manganese catalyst under blue light irradiation with O₂ as the sole oxidant. Featuring mild reaction conditions, the protocol allowed readily available carboxylic acids to be converted into a wide variety of valuable aldehydes, ketones and amides. Mechanistic studies indicated that the decarboxylation and oxygenation involved the formation of active Mn-oxygen species.

Green Chemistry published new progress about 90-64-2. 90-64-2 belongs to alcohols-buliding-blocks, auxiliary class Carboxylic acid,Benzene,Alcohol,Natural product, name is 2-Hydroxy-2-phenylacetic acid, and the molecular formula is C8H8O3, HPLC of Formula: 90-64-2.

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

Aly, Nesma published the artcileCosmetic Potential of a Recombinant 50 kDa Protein, Category: alcohols-buliding-blocks, the publication is Cosmetics (2022), 9(1), 8, database is CAplus.

Collagen and its derivative proteins have been widely used as a major component for cosmetic formulations as a natural ingredient and moisturizer. Most com. available collagens are animal-derived collagen type I and other forms of collagen, such as type III collagen, are far less prevalent in animals, making extraction and purification extremely difficult and expensive. Here, we report the production of a 50 kDa protein produced in yeast that is 100% identical to the N-terminus of the human type III collagen. This recombinant protein has a larger mol. weight than most incumbent recombinant collagen proteins available for personal care applications. We report the industrialization of both the fermentation and purification processes to produce a final recombinant protein product. This final protein product was shown to be safe for general applications to human skin and compatible with common formulation protocols, including ethanol-based formulations. This recombinant collagen type III protein was also shown to uniquely stimulate both collagen type I and type III production and secretion by primary human dermal fibroblasts. The unique combination of biostimulation, compatibility with beauty product formulations and demonstrated com. production, make this novel recombinant type III collagen a good candidate for broad application in the cosmetics industry.

Cosmetics published new progress about 111-29-5. 111-29-5 belongs to alcohols-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Alcohol,Ploymers, name is Pentane-1,5-diol, and the molecular formula is C5H12O2, Category: alcohols-buliding-blocks.

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

Alanthadka, Anitha published the artcileNickel-Catalyzed Double Dehydrogenative Coupling of Secondary Alcohols and β-Amino Alcohols To Access Substituted Pyrroles, SDS of cas: 96-20-8, the publication is Journal of Organic Chemistry (2019), 84(21), 13557-13564, database is CAplus and MEDLINE.

Herein, we demonstrate the first nickel-catalyzed double dehydrogenative condensation of secondary alcs. and β-amino alcs. in one pot to the pyrrole derivatives A series of 2,5- and 2,3,5-substituted pyrroles were obtained in â‰?3% yield, releasing water and hydrogen gas as byproducts. Initial mechanistic studies, including defined Ni catalyst, deuterium labeling experiments, quant. determination of hydrogen gas evaluation, and detection of water generation in the reaction mixture, were performed.

Journal of Organic Chemistry 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 C4H11NO, SDS of cas: 96-20-8.

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

Johnson, Wilbur Jr. published the artcileSafety assessment of alkyl glyceryl ethers as used in cosmetics, Formula: C11H24O3, the publication is International Journal of Toxicology (2013), 32(5S), 5S-21S, database is CAplus and MEDLINE.

A review. Alkyl glyceryl ethers function mostly as skin-conditioning agents in cosmetic products applied to the skin and hair. The Cosmetic Ingredient Review expert panel reviewed the available animal toxicity and clin. data, including the low dermal absorption, and concluded that the alkyl glyceryl ethers are safe in the present practices of use and concentration described in this safety assessment.

International Journal of Toxicology 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, Formula: C11H24O3.

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

Azarani, A. published the artcileElectron transfer reactions between excited diarylmethyl and triarylmethyl carbocations and aromatic donors, Computed Properties of 596-38-3, the publication is Journal of Photochemistry and Photobiology, A: Chemistry (1991), 57(1-3), 175-89, database is CAplus.

The excited singlet states of diarylmethyl and triarylmethyl carbocations were characterized by fluorescence. The dibenzosuberenyl, xanthenyl, and 9-phenylxanthenyl cations are strongly fluorescent and have fluorescence lifetimes in the 30-40 ns range in 2,2,2-trifluoroethanol. The fluorescence of each of these cations is efficiently quenched by a variety of substituted aromatics (e.g., cumene, anisole, toluene) with rate constants in excess of 10⁹ M^-1 s^-1. There is a correlation between the observed rate constants and the oxidation potential of the aromatic quencher which suggests that an electron transfer process occurs to generate a radical/radical cation pair. This hypothesis is confirmed by irradiation of the dibenzosuberenyl cation in the presence of benzyltrimethylsilane. This reaction produces 5-benzyldibenzocycloheptene, which is formed by addition of the benzyl radical produced via cleavage of the silane radical cation to either the dibenzosuberenyl radical or cation. Quenching studies suggest that the efficiency of product formation is controlled by the competition between cage escape and back electron transfer for the initial geminate radical/radical ion pair.

Journal of Photochemistry and Photobiology, A: Chemistry published new progress about 596-38-3. 596-38-3 belongs to alcohols-buliding-blocks, auxiliary class Other Aromatic Heterocyclic,Benzene,Alcohol, name is 9-Phenyl-9H-xanthen-9-ol, and the molecular formula is C19H14O2, Computed Properties of 596-38-3.

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

Schmidt, Tobias published the artcileBiotransformation of trans-1-chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd), Product Details of C3H5F3O, the publication is Toxicology and Applied Pharmacology (2013), 268(3), 343-351, database is CAplus and MEDLINE.

Trans-1-Chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd) is a novel foam blowing and precision cleaning agent with a very low impact for global warming and ozone depletion. trans-HCFO-1233zd also has a low potential for toxicity in rodents and is neg. in genotoxicity testing. The biotransformation of trans-HCFO-1233zd and kinetics of metabolite excretion with urine were assessed in vitro and in animals after inhalation exposures. For in vitro characterization, liver microsomes from rats, rabbits and humans were incubated with trans-HCFO-1233zd. Male Sprague Dawley rats and female New Zealand White rabbits were exposed to 2,000, 5,000 and 10,000 ppm for 6 h and urine was collected for 48 h after the end of the exposure. Study specimens were analyzed for metabolites using ¹⁹F NMR, LC-MS/MS and GC/MS. S-(3,3,3-trifluoro-trans-propenyl)-glutathione was identified as predominant metabolite of trans-HCFO-1233zd in all microsomal incubation experiments in the presence of glutathione. Products of the oxidative biotransformation of trans-HCFO-1233zd were only minor metabolites when glutathione was present. In rats, both 3,3,3-trifluorolactic acid and N-acetyl-(3,3,3-trifluoro-trans-propenyl)-L-cysteine were observed as major urinary metabolites. 3,3,3-Trifluorolactic acid was not detected in the urine of rabbits. Quantitation showed rapid excretion of both metabolites in both species (t_1/2 < 6 h) and the extent of biotransformation of trans-HCFO-1233zd was determined as approx. 0.01% of received dose in rabbits and approx. 0.002% in rats. trans-HCFO-1233zd undergoes both oxidative biotransformation and glutathione conjugation at very low rates. The low extent of biotransformation and the rapid excretion of metabolites formed are consistent with the very low potential for toxicity of trans-HCFO-1233zd in mammals.

Toxicology and Applied Pharmacology 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, Product Details of C3H5F3O.

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

Macsari, Istvan published the artcile3-Oxoisoindoline-1-carboxamides: Potent, State-Dependent Blockers of Voltage-Gated Sodium Channel Na_V1.7 with Efficacy in Rat Pain Models, Related Products of alcohols-buliding-blocks, the publication is Journal of Medicinal Chemistry (2012), 55(15), 6866-6880, database is CAplus and MEDLINE.

The voltage-gated sodium channel Na_V1.7 is believed to be a critical mediator of pain sensation based on clin. genetic studies and pharmacol. results. Clin. utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the optimization, structure-activity relationships, and in vitro and in vivo characterization of a novel series of Na_V1.7 inhibitors based on the oxoisoindoline core. Extensive studies with focus on optimization of Na_V1.7 potency, selectivity over Na_V1.5, and metabolic stability properties produced several interesting oxoisoindoline carboxamides (16A, 26B, 28, 51, 60, and 62) that were further characterized. The oxoisoindoline carboxamides interacted with the local anesthetics binding site. In spite of this, several compounds showed functional selectivity vs. Na_V1.5 of more than 100-fold. This appeared to be a combination of subtype and state-dependent selectivity. Compound 28 showed concentration-dependent inhibition of nerve injury-induced ectopic in an ex vivo DRG preparation from SNL rats. Compounds 16A and 26B demonstrated concentration-dependent efficacy in preclin. behavioral pain models. The oxoisoindoline carboxamides series described here may be valuable for further investigations for pain therapeutics.

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