Month: December 2022

Pye, Cameron R. published the artcileNonclassical Size Dependence of Permeation Defines Bounds for Passive Adsorption of Large Drug Molecules, Safety of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Journal of Medicinal Chemistry (2017), 60(5), 1665-1672, database is CAplus and MEDLINE.

There is a growing number of intracellular protein-protein interactions (PPI’s) with potential therapeutic importance that demand larger ligands than those that neatly fit into most common criteria for “drug-likeness”. Macrocyclic peptides pro-vide the large surface area required to inhibit PPIs and, in principle, avoid many of the pitfalls associated with peptides, including low stability and membrane permeability. However, the design of passively cell-permeable mols. in this space remains a great challenge due to the poorly understood roles of mol. size and lipophilicity in determining passive membrane permeability above MW âˆ?00. Using split-pool combinatorial synthesis, we constructed a library of cyclic, per-N-methlyated peptides spanning a wide range of calculated lipohilicities (0 < AlogP < 8) and mol. weights (âˆ?00 Da < MW < âˆ?200 Da). Assaying mixtures of compounds using the Parallel Artificial Membrane Assay (PAMPA) revealed a steep drop-off in apparent passive permeability with increasing size and a bilinear relationship with lipophilicity. We observed a size dependence of permeability that is in stark disagreement with current permeation models. The lipophilicities required to overcome this size penalty led to poor aqueous solubility, effectively bounding the chem. space of likely passively permeable mols. This understanding provides a new set of design criteria for achieving permeability in larger mol. size regimes and suggests an operational cut-off beyond which passive permeability is constrained by a sharply increasing penalty on permeation through the system.

Journal of Medicinal Chemistry published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Safety of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Borys, Andryj M. published the artcileThe Anionic Pathway in the Nickel-Catalysed Cross-Coupling of Aryl Ethers, Quality Control of 93-04-9, the publication is Angewandte Chemie, International Edition (2021), 60(46), 24659-24667, database is CAplus and MEDLINE.

The Ni-catalyzed cross-coupling of aryl ethers is a powerful method to forge new C-C and C-heteroatom bonds. However, the inert C(sp²)-O bond means that a canonical mechanism that relies on the oxidative addition of the aryl ether to a Ni⁰ center is thermodynamically and kinetically unfavorable, which suggests that alternative mechanisms may be involved. Here, we provide spectroscopic and structural insights into the anionic pathway, which relies on the formation of electron-rich hetero-bimetallic nickelates by adding organometallic nucleophiles to a Ni⁰ center. Assessing the rich co-complexation chem. between Ni(COD)₂ and PhLi has led to the structures and solution-state chem. of a diverse family of catalytically competent lithium nickelates being unveiled. In addition, we demonstrate dramatic solvent and donor effects, which suggest that the cooperative activation of the aryl ether substrate by Ni⁰-ate complexes plays a key role in the catalytic cycle.

Angewandte Chemie, International Edition published new progress about 93-04-9. 93-04-9 belongs to ethers-buliding-blocks, auxiliary class Naphthalene,Ether, name is 2-Methoxynaphthalene, and the molecular formula is C11H10O, Quality Control of 93-04-9.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Gelis, Coralie published the artcileCatalytic Transfer Hydrogenation of Arenes and Heteroarenes, Category: ethers-buliding-blocks, the publication is Chemistry – A European Journal (2020), 26(62), 14090-14094, database is CAplus and MEDLINE.

Transfer hydrogenation reactions are of great interest to reduce diverse mols. under mild reaction conditions. To date, this type of reaction has only been successfully applied to alkenes, alkynes and polarized unsaturated compounds such as ketones, imines, pyridines, etc. The reduction of benzene derivatives by transfer hydrogenation has never been described, which is likely due to the high energy barrier required to dearomatize these compounds In this context, a catalytic transfer hydrogenation reaction for the reduction of benzene derivatives and heteroarenes to form complex 3-dimensional scaffolds bearing various functional groups at room temperature without needing compressed hydrogen gas has been developed.

Chemistry – A European Journal published new progress about 93-04-9. 93-04-9 belongs to ethers-buliding-blocks, auxiliary class Naphthalene,Ether, name is 2-Methoxynaphthalene, and the molecular formula is C11H10O, Category: ethers-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Thoma, Karl published the artcileStudies to determine the critical micelle concentration of local anesthetics, Name: 4-(3-(4-Butoxyphenoxy)propyl)morpholine hydrochloride, the publication is Acta Pharmaceutica Fennica (1984), 93(2), 85-96, database is CAplus.

The critical micelle concentrations of local anesthetics such as cyclomethycaine sulfate  [6202-05-7], Psicaine-neu-HCl  [69343-45-9], cocaine-HCl  [53-21-4], etc., were determined by using tensiometry and potentiometry and spectrophotometry of some anesthetics. The nonionic polidocanol  [9002-92-0] had a critical micellar concentrations of 1 × 10^-4 mol/L found both by tensiometry and dye sorption methods. The dissociating local anesthetics show critical micelle concentrations from 0.046-5.5% in aqueous solution

Acta Pharmaceutica Fennica published new progress about 637-58-1. 637-58-1 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is 4-(3-(4-Butoxyphenoxy)propyl)morpholine hydrochloride, and the molecular formula is C18H34N4O5S, Name: 4-(3-(4-Butoxyphenoxy)propyl)morpholine hydrochloride.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Thoma, K. published the artcileColloid association and biological availability of local anesthetics. Part 1. Surface activity studies on critical micelle concentrations, Formula: C17H28ClNO3, the publication is Pharmaceutica Acta Helvetiae (1988), 63(2), 34-9, database is CAplus and MEDLINE.

Surface activities of local anesthetics are reported. The ability to associate to micelles in aqueous solution was found with 9 benzoic acid esters, 3 anilides or acid amides, and for all compounds with ether structures. Twelve of the 29 investigated compounds do not associate to micelles. The critical micelle concentrations (CMC) in 0.9% NaCl solution range from 6.0·10^-5 mol/L for the nonionic polydocanol to 6.6·10^-2 mol/L for cornecaine-HCl. Cyclomethycaine has the lowest CMC (4.3·10^-4 mol/L) of basic local anesthetics.

Pharmaceutica Acta Helvetiae published new progress about 637-58-1. 637-58-1 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is 4-(3-(4-Butoxyphenoxy)propyl)morpholine hydrochloride, and the molecular formula is C9H12BClO3, Formula: C17H28ClNO3.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Kim, Jung-Sik published the artcileSynthesis and characterization of organic light-emitting copolymers containing naphthalene, HPLC of Formula: 146370-51-6, the publication is Macromolecular Research (2009), 17(2), 91-98, database is CAplus.

Conjugated PPV-derived block copolymers containing 2-ethylhexyloxynaphthalene unit were synthesized and characterized in this study. The resulting polymers were soluble in common organic solvents and showed good thermal stabilities. The weight-average mol. weights (M_w) of the copolymers ranged from 246,000 to 475,000 with PDIs of 1.3âˆ?.1. The optical properties of these polymers, measured both in a chloroform solution and on a film, showed a maximum absorption at 405âˆ?76 nm for Copolymers I∼VIII. In the PL spectra, Copolymers I∼VIII showed maximum peaks at 510âˆ?66 nm. The HOMOs, LUMOs and band gaps of the PPV derivatives of Copolymers I∼VIII were 5.30âˆ?.77, 3.04âˆ?.24, and 2.5âˆ?.2 eV, resp. The multi-layered, light-emitting diodes of ITO/PEDOT/copolymers/LiF/Al exhibited turn-on voltages of 6âˆ?.5 V. Copolymer VIII exhibited the maximum brightness of 3657 cd/m². Particularly, Copolymer VII, with an identical composition of MEH-PPV and naphthalene-PPV, showed a maximum luminance efficiency and power efficiency of 2.63 cd/A and 1.06 lm/W, resp.

Macromolecular Research published new progress about 146370-51-6. 146370-51-6 belongs to ethers-buliding-blocks, auxiliary class Benzene,Ether, name is 1-((2-Ethylhexyl)oxy)-4-methoxybenzene, and the molecular formula is C15H24O2, HPLC of Formula: 146370-51-6.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Claffey, Michelle M. published the artcileApplication of Structure-Based Drug Design and Parallel Chemistry to Identify Selective, Brain Penetrant, In Vivo Active Phosphodiesterase 9A Inhibitors, Recommanded Product: 3-Phenoxyazetidine hydrochloride, the publication is Journal of Medicinal Chemistry (2012), 55(21), 9055-9068, database is CAplus and MEDLINE.

Phosphodiesterase 9A inhibitors have shown activity in preclin. models of cognition with potential application as novel therapies for treating Alzheimer’s disease. Our clin. candidate, PF-04447943 (2), demonstrated acceptable CNS permeability in rats with modest asymmetry between central and peripheral compartments (free brain/free plasma = 0.32; CSF/free plasma = 0.19) yet had physicochem. properties outside the range associated with traditional CNS drugs. To address the potential risk of restricted CNS penetration with 2 in human clin. trials, we sought to identify a preclin. candidate with no asymmetry in rat brain penetration and that could advance into development. Merging the medicinal chem. strategies of structure-based design with parallel chem., a novel series of PDE9A inhibitors was identified that showed improved selectivity over PDE1C. Optimization afforded preclin. candidate 19 that demonstrated free brain/free plasma â‰? in rat and reduced microsomal clearance along with the ability to increase cyclic guanosine monophosphosphate levels in rat CSF.

Journal of Medicinal Chemistry published new progress about 301335-39-7. 301335-39-7 belongs to ethers-buliding-blocks, auxiliary class Azetidine,Salt,Benzene,Ether, name is 3-Phenoxyazetidine hydrochloride, and the molecular formula is C9H12ClNO, Recommanded Product: 3-Phenoxyazetidine hydrochloride.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Bezencon, Olivier published the artcileDiscovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies, SDS of cas: 2358-54-5, the publication is Journal of Medicinal Chemistry (2017), 60(23), 9769-9789, database is CAplus and MEDLINE.

The authors report the discovery and pharmacol. characterization of N-(1-benzyl-1H-pyrazol-3-yl)-2-phenylacetamide derivatives as potent, selective, brain-penetrating T-type calcium channel blockers. Optimization focused mainly on solubility, brain penetration, and the search for an aminopyrazole metabolite that would be neg. in an Ames test. This resulted in the preparation and complete characterization of compound 66b (ACT-709478 (N-(1-((5-cyanopyridin-2-yl)methyl)-1H-pyrazol-3-yl)-2-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)acetamide)), which has been selected as a clin. candidate.

Journal of Medicinal Chemistry published new progress about 2358-54-5. 2358-54-5 belongs to ethers-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Aliphatic hydrocarbon chain,Alcohol,Ether, name is 2-(2,2,2-Trifluoroethoxy)ethanol, and the molecular formula is C4H7F3O2, SDS of cas: 2358-54-5.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Musdal, Yaman published the artcileFDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1, SDS of cas: 637-58-1, the publication is Chemico-Biological Interactions (2013), 205(1), 53-62, database is CAplus and MEDLINE.

Glutathione transferase P1-1 (GST P1-1) is often overexpressed in tumor cells and is regarded as a contributor to their drug resistance. Inhibitors of GST P1-1 are expected to counteract drug resistance and may therefore serve as adjuvants in the chemotherapy of cancer by increasing the efficacy of cytostatic drugs. Finding useful inhibitors among compounds used for other indications would be a shortcut to clin. applications and a search for GST P1-1 inhibitors among approved drugs and other compounds was therefore conducted. We tested 1040 FDA-approved compounds as inhibitors of the catalytic activity of purified human GST P1-1 in vitro. We identified chlorophyllide, merbromine, hexachlorophene, and ethacrynic acid as the most effective GST P1-1 inhibitors with IC₅₀ values in the low micromolar range. For comparison, these compounds were even more potent in the inhibition of human GST A3-3, an enzyme implicated in steroid hormone biosynthesis. In distinction from the other inhibitors, which showed conventional inhibition patterns, the competitive inhibitor ethacrynic acid elicited strong kinetic cooperativity in the glutathione saturation of GST P1-1. Apparently, ethacrynic acid serves as an allosteric inhibitor of the enzyme. In their own right, the compounds investigated are less potent than desired for adjuvants in cancer chemotherapy, but the structures of the most potent inhibitors could serve as leads for the synthesis of more efficient adjuvants.

Chemico-Biological Interactions published new progress about 637-58-1. 637-58-1 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is 4-(3-(4-Butoxyphenoxy)propyl)morpholine hydrochloride, and the molecular formula is C17H28ClNO3, SDS of cas: 637-58-1.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Peng, Ting published the artcileDiscovery of a Novel Small-Molecule Inhibitor Disrupting TRBP-Dicer Interaction against Hepatocellular Carcinoma via the Modulation of microRNA Biogenesis, Recommanded Product: (2-Methoxyphenyl)methanamine, the publication is Journal of Medicinal Chemistry (2022), 65(16), 11010-11033, database is CAplus and MEDLINE.

MicroRNAs (miRNAs) are key players in human hepatocellular carcinoma (HCC) tumorigenesis. Therefore, small mols. targeting components of miRNA biogenesis may provide new therapeutic means for HCC treatment. By a high-throughput screening and structural simplification, we identified a small mol., CIB-3b (I), which suppresses the growth and metastasis of HCC in vitro and in vivo by modulating expression profiles of miRNAome and proteome in HCC cells. Mechanistically, CIB-3b phys. binds to transactivation response (TAR) RNA-binding protein 2 (TRBP) and disrupts the TRBP-Dicer interaction, thereby altering the activity of Dicer and mature miRNA production Structure-activity relationship study via the synthesis of 45 CIB-3b derivatives showed that some compounds exhibited a similar inhibitory effect on miRNA biogenesis to CIB-3b. These results support TRBP as a potential therapeutic target in HCC and warrant further development of CIB-3b along with its analogs as a novel therapeutic strategy for the treatment of HCC.

Journal of Medicinal Chemistry published new progress about 6850-57-3. 6850-57-3 belongs to ethers-buliding-blocks, auxiliary class Amine,Benzene,Ether, name is (2-Methoxyphenyl)methanamine, and the molecular formula is C8H11NO, Recommanded Product: (2-Methoxyphenyl)methanamine.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem