Month: November 2022

Gawel, Justyna M. published the artcilePTG-0861: A novel HDAC6-selective inhibitor as a therapeutic strategy in acute myeloid leukaemia, Category: quinuclidine, the publication is European Journal of Medicinal Chemistry (2020), 112411, database is CAplus and MEDLINE.

Dysregulated Histone Deacetylase (HDAC) activity across multiple human pathologies have highlighted this family of epigenetic enzymes as critical druggable targets, amenable to small mol. intervention. While efficacious, current approaches using non-selective HDAC inhibitors (HDACi) have been shown to cause a range of undesirable clin. toxicities. To circumvent this, recent efforts have focused on the design of highly selective HDACi as a novel therapeutic strategy. Beyond roles in regulating transcription, the unique HDAC6 (with two catalytic domains) regulates the deacetylation of α-tubulin; promoting growth factor-controlled cell motility, cell division, and metastatic hallmarks. Recent studies have linked aberrant HDAC6 function in various hematol. cancers including acute myeloid leukemia and multiple myeloma. Herein, we report the discovery, in vitro characterization, and biol. evaluation of PTG-0861 (JG-265), a novel HDAC6-selective inhibitor with strong isoenzyme-selectivity (∼36x ) and low nanomolar potency (IC₅₀ = 5.92 nM) against HDAC6. This selectivity profile was rationalized via in silico docking studies and also observed in cellulo through cellular target engagement. Moreover, PTG-0861 achieved relevant potency against several blood cancer cell lines (e.g. MV4-11, MM1S), while showing limited cytotoxicity against non-malignant cells (e.g. NHF, HUVEC) and CD-1 mice. In examining compound stability and cellular permeability, PTG-0861 revealed a promising in vitro pharmacokinetic (PK) profile. Altogether, in this study we identified a novel and potent HDAC6-selective inhibitor (∼4x more selective than current clin. standards – citarinostat, ricolinostat), which achieves cellular target engagement, efficacy in hematol. cancer cells with a promising safety profile and in vitro PK.

European Journal of Medicinal Chemistry published new progress about 20029-52-1. 20029-52-1 belongs to quinuclidine, auxiliary class Carboxylic acid,Benzene, name is 4-Cyclohexylbenzoic acid, and the molecular formula is C13H16O2, Category: quinuclidine.

Referemce:
https://en.wikipedia.org/wiki/Quinuclidine,
Quinuclidine | C7H13N | ChemSpider

Qiu, Wenting published the artcileA Mild, General, Metal-Free Method for Desulfurization of Thiols and Disulfides Induced by Visible-Light, Product Details of C6H10O2S, the publication is Chinese Journal of Chemistry (2021), 39(5), 1255-1258, database is CAplus.

A visible-light-induced metal-free desulfurization method for thiols and disulfides was explored. This radical desulfurization featured mild conditions, robustness, and excellent functionality compatibility. It was successfully applied not only to the desulfurization of small mols., but also to peptides.

Chinese Journal of Chemistry published new progress about 162515-68-6. 162515-68-6 belongs to quinuclidine, auxiliary class Thiol,Carboxylic acid,Aliphatic cyclic hydrocarbon, name is 2-(1-(Mercaptomethyl)cyclopropyl)acetic acid, and the molecular formula is C6H10O2S, Product Details of C6H10O2S.

Referemce:
https://en.wikipedia.org/wiki/Quinuclidine,
Quinuclidine | C7H13N | ChemSpider

Tang, Yitian published the artcileEfficient Synthesis of γ-Lactones by Cobalt-Catalyzed Carbonylative Ring Expansion of Oxetanes under Syngas Atmosphere, Formula: C6H10O2S, the publication is ChemCatChem (2020), 12(23), 5898-5902, database is CAplus.

A practical route from oxetanes or thietanes to γ-(thio)butyrolactones via solvated-proton-assisted cobalt-catalyzed carbonylative ring expansion under syngas atm. were reported. A wide variety of γ-(thio)butyrolactones were afforded in a good to excellent yields. The versatility of this method were well demonstrated in the synthesis of intermediates towards the natural product Arctigenin as well as the pharmaceuticals Baclofen and Montelukast. The observed promoting effect of glycol ether solvent were rationally interpreted.

ChemCatChem published new progress about 162515-68-6. 162515-68-6 belongs to quinuclidine, auxiliary class Thiol,Carboxylic acid,Aliphatic cyclic hydrocarbon, name is 2-(1-(Mercaptomethyl)cyclopropyl)acetic acid, and the molecular formula is C6H12N2O, Formula: C6H10O2S.

Referemce:
https://en.wikipedia.org/wiki/Quinuclidine,
Quinuclidine | C7H13N | ChemSpider

White, James D. published the artcileIron catalyzed enantioselective sulfa-Michael addition: a four-step synthesis of the anti-asthma agent Montelukast, SDS of cas: 162515-68-6, the publication is Chemical Science (2014), 5(6), 2200-2204, database is CAplus.

A salen ligand based on a chiral cis-2,5-diaminobicyclo[2.2.2]octane scaffold forms an iron(iii) complex with ferric chloride which catalyzed asym. addition of thiols to α,β-unsaturated ketones under mild conditions. The reaction (sulfa-Michael addition) produces β-thioketones in excellent yield and high enantiomeric excess from a wide range of aliphatic and aromatic thiols using chalcones and other conjugated enones as Michael acceptors. With α-substituted α,β-unsaturated ketones as acceptors, the addition showed strong preference (typically >50 : 1) for the syn diastereomer over the anti product. An asym. synthesis of (R)-Montelukast, the sodium salt of which is the com. anti-asthma drug Singulair, was devised using conjugate addition of a thiol catalyzed by our iron(III)-salen complex to an α,β-unsaturated ketone synthesized in a four-component, one-pot tandem Michael-aldol condensation. The reaction sequence to (R)-Montelukast proceeded in 72% overall yield over four steps from com. available materials. A mechanism for our catalyzed asym. sulfa-Michael addition was advance which coordinates the enone acceptor to the metal center of the iron-salen complex in an open lower quadrant under the bicyclic scaffold, thereby exposing only the si face of the double bond to attack by the external nucleophilic thiol. Prior internal coordination of the thiol to the metal center of the complex is proposed based on spectroscopic and chem. evidence and leads to activation of the catalyst through a trans ligand effect.

Chemical Science published new progress about 162515-68-6. 162515-68-6 belongs to quinuclidine, auxiliary class Thiol,Carboxylic acid,Aliphatic cyclic hydrocarbon, name is 2-(1-(Mercaptomethyl)cyclopropyl)acetic acid, and the molecular formula is C9H20Cl2Si, SDS of cas: 162515-68-6.

Referemce:
https://en.wikipedia.org/wiki/Quinuclidine,
Quinuclidine | C7H13N | ChemSpider

Hatter, Christine B. published the artcileMicromechanical response of two-dimensional transition metal carbonitride (MXene) reinforced epoxy composites, Name: 4,4-Diaminodicyclohexyl methane, the publication is Composites, Part B: Engineering (2020), 107603, database is CAplus.

MXenes have attracted much attention as fillers in polymer composites due to their superior elec. and mech. properties making them ideal for creating multifunctional composites. In this work, Ti₃CN-epoxy composites were prepared via solvent processing and cured with amine-based hardener. The effects of Ti₃CN content in the epoxy system on the thermal degradation behavior and micromech. properties were investigated. The extent of intercalation of epoxy between MXene flakes was analyzed by transmission electron microscopy. Nanoindentation anal. of MXene-epoxy composites exhibited improved mech. properties with increasing MXene content with highest increase to 12.8 GPa Young’s modulus for 90 wt% Ti₃CN. An increase in creep resistance of composites was observed at maximum loading of Ti₃CN by 46% compared to neat epoxy.

Composites, Part B: Engineering published new progress about 1761-71-3. 1761-71-3 belongs to quinuclidine, auxiliary class Ploymers, name is 4,4-Diaminodicyclohexyl methane, and the molecular formula is C13H26N2, Name: 4,4-Diaminodicyclohexyl methane.

Referemce:
https://en.wikipedia.org/wiki/Quinuclidine,
Quinuclidine | C7H13N | ChemSpider

Zhang, H. J. published the artcileEffect of free-volume holes on static mechanical properties of epoxy resins studied by positron annihilation and PVT experiments, Quality Control of 1761-71-3, the publication is Polymer (2020), 122225pp., database is CAplus.

The tensile, flexural, and fracture toughness properties of seven chem. different amine-cured epoxy resins were studied. Positron annihilation lifetime and pressure-volume-temperature (PVT) experiments were performed on each epoxy resin to characterize the average size and fraction, resp., of free-volume holes. A neg. correlation between hole fraction and hole size was revealed for these chem. different epoxy resins. Better tensile and flexural mech. properties (higher tensile modulus and lower tensile strain at break; higher flexural modulus, higher flexural strength, and lower flexural strain at break) were clearly observed for epoxy resins with smaller hole size and higher hole fraction. However, no clear relationship between fracture toughness and hole properties was found. The correlations between (tensile and flexural) static mech. properties and hole properties for chem. different epoxy resins should provide guidance for further improvements in the mech. properties of carbon fiber-reinforced polymers.

Polymer published new progress about 1761-71-3. 1761-71-3 belongs to quinuclidine, auxiliary class Ploymers, name is 4,4-Diaminodicyclohexyl methane, and the molecular formula is C18H20N2O12, Quality Control of 1761-71-3.

Referemce:
https://en.wikipedia.org/wiki/Quinuclidine,
Quinuclidine | C7H13N | ChemSpider

Zhang, H. J. published the artcileEffect of Free-Volume Hole Fraction on Dynamic Mechanical Properties of Epoxy Resins Investigated by Pressure-Volume-Temperature Technique, COA of Formula: C13H26N2, the publication is Journal of Physical Chemistry B (2020), 124(9), 1824-1832, database is CAplus and MEDLINE.

Dynamic mech. anal. experiments were carried out to investigate the mech. properties of four types of chem. different epoxy resins. Pressure-volume-temperature (PVT) experiments were performed to determine the free-volume hole fraction (h_PVT) of each epoxy resin using the Simha-Somcynsky lattice-hole theory. Using the Williams-Landel-Ferry equation, the correlations between the relative hole fraction (1 – h_PVT^T_r/h_PVT, where h_PVT^T_r is the hole fraction at a reference temperature T_r) and four typical parameters reflecting dynamic mech. properties [storage modulus (E’), loss modulus (E”), damping factor (tanδ), and complex viscosity (|η*|)] were studied at from T_g(PVT) (the glass transition temperature determined by PVT data) to T_g(PVT) + 100°C. At from T_g(Eonset‘₎ (temperature corresponding to the intersection of the two tangent fitting lines in the E'(T) curve indicating the glassy-state and glass-transition stages) to T_g(PVT) + 100°C, the variations in the four dynamic mech. parameters with a relative hole fraction could be separated into two distinct categories: (i) log[E'(T)] and log[|η*|(T)] decreased linearly to their min. values and then remained nearly unchanged with increasing relative hole fraction, and (ii) log[E”(T)] and log[tanδ(T)] first increased monotonically to their maximum values and then decreased linearly with the increasing relative hole fraction. This study demonstrates that the PVT technique is a feasible and reliable exptl. method to determine the hole fractions of thermoset polymers.

Journal of Physical Chemistry B published new progress about 1761-71-3. 1761-71-3 belongs to quinuclidine, auxiliary class Ploymers, name is 4,4-Diaminodicyclohexyl methane, and the molecular formula is 0, COA of Formula: C13H26N2.

Referemce:
https://en.wikipedia.org/wiki/Quinuclidine,
Quinuclidine | C7H13N | ChemSpider

Kashida, Hiromu published the artcileInsulator base pairs for lighting-up perylenediimide in a DNA duplex, Related Products of quinuclidine, the publication is Chemistry – A European Journal (2010), 16(38), 11554-11557, S11554/1-S11554/18, database is CAplus and MEDLINE.

Perylenediimide (PDI) is highly quenched by nucleobases, which greatly restricts its application as a fluorescent probe. Here, the authors propose “insulator base pairs” tethering cyclohexane ring through D-threoninol. When “insulator base pairs” were inserted between PDI and nucleobases, the quantum yield of PDI drastically increased several thousand-fold. The “insulator base pairs” reported here also have the potential to increase the quantum yields of other fluorophores.

Chemistry – A European Journal published new progress about 20029-52-1. 20029-52-1 belongs to quinuclidine, auxiliary class Carboxylic acid,Benzene, name is 4-Cyclohexylbenzoic acid, and the molecular formula is C13H16O2, Related Products of quinuclidine.

Referemce:
https://en.wikipedia.org/wiki/Quinuclidine,
Quinuclidine | C7H13N | ChemSpider

Quattropani, Anna published the artcilePharmacophore-Based Design of Novel Oxadiazoles as Selective Sphingosine-1-phosphate (S1P) Receptor Agonists with in vivo Efficacy, Recommanded Product: 4-Cyclohexylbenzoic acid, the publication is ChemMedChem (2015), 10(4), 688-714, database is CAplus and MEDLINE.

Sphingosine-1-phosphate (S1P) receptor agonists have shown promise as therapeutic agents for multiple sclerosis (MS) due to their regulatory roles within the immune, central nervous system, and cardiovascular system. Here, the design and optimization of novel [1,2,4]oxadiazole derivatives as selective S1P receptor agonists are described. The structure-activity relation exploration was carried out on the three dominant segments of the series: modification of the polar head group (P), replacement of the oxadiazole linker (L) with different five-membered heterocycles, and the use of diverse 2,2′-disubstituted biphenyl moieties as the hydrophobic tail (H). All three segments have a significant impact on potency, S1P receptor subtype selectivity, physicochem. properties, and in vitro absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of the compounds From these optimization studies, a selective S1P₁ agonist, N-methyl-N-(4-{5-[2-methyl-2′-(trifluoromethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzyl)glycine (45), and a dual S1P_1,5 agonist, N-methyl-N-(3-{5-[2′-methyl-2-(trifluoromethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzyl)glycine (49), emerged as frontrunners. These compounds distribute predominantly in lymph nodes and brain over plasma and induce long lasting decreases in lymphocyte count after oral administration. When evaluated head-to-head in an exptl. autoimmune encephalomyelitis mouse model, together with the marketed drug fingolimod, a pan-S1P receptor agonist, S1P_1,5 agonist 49 demonstrated comparable efficacy while S1P₁-selective agonist 45 was less potent. Compound 49 is not a prodrug, and its improved property profile should translate into a safer treatment of relapsing forms of MS.

ChemMedChem published new progress about 20029-52-1. 20029-52-1 belongs to quinuclidine, auxiliary class Carboxylic acid,Benzene, name is 4-Cyclohexylbenzoic acid, and the molecular formula is C13H16O2, Recommanded Product: 4-Cyclohexylbenzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Quinuclidine,
Quinuclidine | C7H13N | ChemSpider

Chaudhari, Chandan published the artcileOne-pot synthesis of cyclohexylamine and N-aryl pyrroles via hydrogenation of nitroarenes over the Pd_0.5Ru_0.5-PVP catalyst, Category: quinuclidine, the publication is New Journal of Chemistry (2021), 45(22), 9743-9746, database is CAplus.

The direct synthesis of cyclohexylamine via the hydrogenation of nitrobenzene over monometallic (Pd, Ru or Rh) and bimetallic (Pd_xRu_1-x) catalysts was studied. The Pd_0.5Ru_0.5-PVP catalyst was the most effective catalyst for this reaction. The catalyst can be reused and applied for the synthesis of N-aryl pyrroles I (R = Ph, 4-chlorophenyl, pyridin-3-yl, etc.) and quinoxalines such as 2,3-diphenylquinoxaline and 2,3-diphenyl-1,2,3,4-tetrahydroquinoxaline from nitrobenzenes RNO₂.

New Journal of Chemistry published new progress about 1761-71-3. 1761-71-3 belongs to quinuclidine, auxiliary class Ploymers, name is 4,4-Diaminodicyclohexyl methane, and the molecular formula is C13H26N2, Category: quinuclidine.

Referemce:
https://en.wikipedia.org/wiki/Quinuclidine,
Quinuclidine | C7H13N | ChemSpider