Month: October 2022

Dong, Yan; Li, Kehuang; Xu, Zhixiang; Ma, Haikuo; Zheng, Jiyue; Hu, Zhilin; He, Sudan; Wu, Yiyuan; Sun, Zhijian; Luo, Lusong; Li, Jiajun; Zhang, Hongjian; Zhang, Xiaohu published the artcile< Exploration of the linkage elements of porcupine antagonists led to potent Wnt signaling pathway inhibitors>, Product Details of C12H18BNO2, the main research area is protein palmitoyltransferase Porcupine antagonist synthesis inhibitor Wnt signaling secretion; Antagonist; Cancer therapy; Porcupine; Scaffold hybridization; Wnt signaling pathway.

The Wnt signaling pathway is a pivotal developmental pathway. It operates through control of cellular functions such as proliferation, differentiation, migration and polarity. Aberrant Wnt signaling has been implicated in the formation and metastasis of tumors. Porcupine is a component of the Wnt signaling pathway. It is a member of the membrane-bound O-acyltransferase family of proteins. Porcupine catalyzes the palmitoylation of Wnt proteins, a process which is essential to their secretion and activity. Here we report a novel series of compounds obtained by a scaffold hybridization strategy from two known porcupine inhibitor classes. The leading compound 62 demonstrated subnanomolar (IC50 0.11 nM) inhibition of Wnt signaling in a paracrine cellular reporter gene assay. Compound 62 also potently inhibited Wnt secretion into culture medium, an indication of direct inhibition of the porcupine protein. Furthermore, compound 62 showed excellent chem., plasma and liver microsomal stabilities. Collectively, these results strongly support further optimization of this novel scaffold to develop better Wnt pathway inhibitors.

Bioorganic & Medicinal Chemistry published new progress about Amide group (in Porcupine antagonists). 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Product Details of C12H18BNO2.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Tian, Ya-Ming; Guo, Xiao-Ning; Krummenacher, Ivo; Wu, Zhu; Nitsch, Joern; Braunschweig, Holger; Radius, Udo; Marder, Todd B. published the artcile< Visible-Light-Induced Ni-Catalyzed Radical Borylation of Chloroarenes>, Safety of 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, the main research area is chloro nickel carbene preparation catalyzed radical borylation chloroarene; crystal structure imidazolylidene nickel chloride; mol structure imidazolylidene nickel chloride; arylborane preparation.

A highly selective and general photoinduced C-Cl borylation protocol that employs [Ni(IMes)2] (IMes = 1,3-dimesitylimidazoline-2-ylidene) for the radical borylation of chloroarenes is reported. This photoinduced system operates with visible light (400 nm) and achieves borylation of a wide range of chloroarenes with B2pin2 at room temperature in excellent yields and with high selectivity, thereby demonstrating its broad utility and functional group tolerance. Mechanistic studies suggest that the borylation reactions proceed via a radical process. EPR studies demonstrate that [Ni(IMes)2] undergoes very fast Cl atom abstraction from aryl chlorides to give [Ni(I)(IMes)2Cl] and aryl radicals. Control experiments indicate that light promotes the reaction of [Ni(I)(IMes)2Cl] with aryl chlorides generating addnl. aryl radicals and [Ni(II)(IMes)2Cl2]. The aryl radicals react with an anionic sp2-sp3 diborane [B2pin2(OMe)]- formed from B2pin2 and KOMe to yield the corresponding borylation product and the [Bpin(OMe)]•- radical anion, which reduces [Ni(II)(IMes)2Cl2] under irradiation to regenerate [Ni(I)(IMes)2Cl] and [Ni(IMes)2] for the next catalytic cycle.

Journal of the American Chemical Society published new progress about Aryl chlorides Role: RCT (Reactant), RACT (Reactant or Reagent). 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Safety of 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Wang, Shu; Beech, Haley K.; Bowser, Brandon H.; Kouznetsova, Tatiana B.; Olsen, Bradley D.; Rubinstein, Michael; Craig, Stephen L. published the artcile< Mechanism Dictates Mechanics: A Molecular Substituent Effect in the Macroscopic Fracture of a Covalent Polymer Network>, Electric Literature of 627-27-0, the main research area is dictate mechanic macroscopic fracture covalent polymer network.

The fracture of rubbery polymer networks involves a series of mol. events, beginning with conformational changes along the polymer backbone and culminating with a chain scission reaction. Here, we report covalent polymer gels in which the macroscopic fracture “”reaction”” is controlled by mechanophores embedded within mech. active network strands. We synthesized poly(ethylene glycol) (PEG) gels through the end-linking of azide-terminated tetra-arm PEG (Mn = 5 kDa) with bis-alkyne linkers. Networks were formed under identical conditions, except that the bis-alkyne was varied to include either a cis-diaryl (1) or cis-dialkyl (2) linked cyclobutane mechanophore that acts as a mechanochem. “”weak link”” through a force-coupled cycloreversion. A control network featuring a bis-alkyne without cyclobutane (3) was also synthesized. The networks show the same linear elasticity (G’ = 23-24 kPa, 0.1-100 Hz) and equilibrium mass swelling ratios (Q = 10-11 in tetrahydrofuran), but they exhibit tearing energies that span a factor of 8 (3.4 J, 10.6, and 27.1 J·m-2 for networks with 1, 2, and 3, resp.). The difference in fracture energy is well-aligned with the force-coupled scission kinetics of the mechanophores observed in single-mol. force spectroscopy experiments, implicating local resonance stabilization of a diradical transition state in the cycloreversion of 1 as a key determinant of the relative ease with which its network is torn. The connection between macroscopic fracture and a small-mol. reaction mechanism suggests opportunities for mol. understanding and optimization of polymer network behavior.

Journal of the American Chemical Society published new progress about Azide-alkyne 1,3-dipolar cycloaddition reaction. 627-27-0 belongs to class alcohols-buliding-blocks, and the molecular formula is C4H8O, Electric Literature of 627-27-0.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Caiger, Lewis; Sinton, Conar; Constantin, Timothee; Douglas, James J.; Sheikh, Nadeem S.; Julia, Fabio; Leonori, Daniele published the artcile< Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon>, Application In Synthesis of 627-27-0, the main research area is alkyl alc preparation; formaldehyde alkyl iodide radical hydroxymethylation photocatalyst.

Here, a strategy that couples alkyl iodide building blocks with formaldehyde through the use of photocatalysis and a phosphine additive was reported. Halogen-atom transfer (XAT) from α-aminoalkyl radicals was leveraged to convert the iodide into the corresponding open-shell species, while its following addition to formaldehyde was rendered irreversible by trapping the transient O-radical with PPh3. This event delivered a phosphoranyl radical that re-generates the alkyl radical and provided the hydroxymethylated product.

Chemical Science published new progress about Alcohols Role: SPN (Synthetic Preparation), PREP (Preparation). 627-27-0 belongs to class alcohols-buliding-blocks, and the molecular formula is C4H8O, Application In Synthesis of 627-27-0.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Chmiel, Alyah F.; Williams, Oliver P.; Chernowsky, Colleen P.; Yeung, Charles S.; Wickens, Zachary K. published the artcile< Non-innocent Radical Ion Intermediates in Photoredox Catalysis: Parallel Reduction Modes Enable Coupling of Diverse Aryl Chlorides>, Synthetic Route of 627-27-0, the main research area is radical ion intermediates photoredox Catalysis parallel reduction mode.

We describe a photocatalytic system that elicits potent photoreductant activity from conventional photocatalysts by leveraging radical anion intermediates generated in situ. The combination of an isophthalonitrile photocatalyst and sodium formate promotes diverse aryl radical coupling reactions from abundant but difficult to reduce aryl chloride substrates. Mechanistic studies reveal two parallel pathways for substrate reduction both enabled by a key terminal reductant byproduct, carbon dioxide radical anion.

Journal of the American Chemical Society published new progress about Borylation (photochem.). 627-27-0 belongs to class alcohols-buliding-blocks, and the molecular formula is C4H8O, Synthetic Route of 627-27-0.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Zhang, Chenghua; Wu, Keliang; Huang, Long; Sun, Kenan; Zou, Yurong; Xiong, Zhihui; Li, Bingke published the artcile< Virtual Screening and Discovery of Matrix Metalloproteinase-12 Inhibitors by Swarm Intelligence Optimization Algorithm-Based Machine Learning>, COA of Formula: C19H16O, the main research area is screening MMP inhibitor swarm intelligence optimization algorithm machine learning.

Matrix metalloproteinase-12 (MMP-12) is an attractive therapeutic target for drug design and discovery for many human conditions. In this study, six swarm intelligence optimization algorithms were applied to optimize the parameters of the model generated using the LibSVM toolkit in MATLAB to identify potential MMP-12 inhibitors (MMP-12is); six types of optimized support vector machine (SVM) models were established. The highest prediction accuracy obtained was 98.89%, which was equivalent to the effect of the optimal “”RF+opt”” model. All six models passed the Y-randomization test and showed excellent performance with reliable results. Virtual screening identified 371 mols. with a predictive probability score greater than 0.9. The optimized SVM models, in addition to “”RF+opt”” and “”SVM2″” models, were combined to establish a consistency evaluation system. Our results revealed six non-toxic potential MMP-12is. This process provides a strong theor. basis for the design, synthesis, and development of novel drugs targeting MMP-12.

ChemistrySelect published new progress about Algorithm. 76-84-6 belongs to class alcohols-buliding-blocks, and the molecular formula is C19H16O, COA of Formula: C19H16O.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Saeed, Mohamed E. M.; Kadioglu, Onat; Greten, Henry Johannes; Yildirim, Adem; Mayr, Katharina; Wenz, Frederik; Giordano, Frank A.; Efferth, Thomas published the artcile< Drug repurposing using transcriptome sequencing and virtual drug screening in a patient with glioblastoma>, Electric Literature of 1492-18-8, the main research area is aclarubicin idarubicin anticancer agent cytotoxicity BRAF PIK3R1 mutation glioblastoma; Drug repurposing; Precision medicine; Targeted chemotherapy; Virtual drug screening.

Precision medicine and drug repurposing are attractive strategies, especially for tumors with worse prognosis. Glioblastoma is a highly malignant brain tumor with limited treatment options and short survival times. We identified novel BRAF (47-438del) and PIK3R1 (G376R) mutations in a glioblastoma patient by RNA-sequencing. The protein expression of BRAF and PIK3R1 as well as the lack of EGFR expression as analyzed by immunohistochem. corroborated RNA-sequencing data. The expression of addnl. markers (AKT, SRC, mTOR, NF-κB, Ki-67) emphasized the aggressiveness of the tumor. Then, we screened a chem. library of > 1500 FDA-approved drugs and > 25,000 novel compounds in the ZINC database to find established drugs targeting BRAF47-438del and PIK3R1-G376R mutated proteins. Several compounds (including anthracyclines) bound with higher affinities than the control drugs (sorafenib and vemurafenib for BRAF and PI-103 and LY-294,002 for PIK3R1). Subsequent cytotoxicity analyses showed that anthracyclines might be suitable drug candidates. Aclarubicin revealed higher cytotoxicity than both sorafenib and vemurafenib, whereas idarubicin and daunorubicin revealed higher cytotoxicity than LY-294,002. Liposomal formulations of anthracyclines may be suitable to cross the blood brain barrier. In conclusion, we identified novel small mols. via a drug repurposing approach that could be effectively used for personalized glioblastoma therapy especially for patients carrying BRAF47-438del and PIK3R1-G376R mutations.

Investigational New Drugs published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (ABCA13). 1492-18-8 belongs to class alcohols-buliding-blocks, and the molecular formula is C20H21CaN7O7, Electric Literature of 1492-18-8.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Ghersi, Dario; Genaro-Mattos, Thiago C. published the artcile< Identifying Molecular Fragments That Drive 7-Dehydrocholesterol Elevation>, Quality Control of 434-16-2, the main research area is cholesterol metabolism 7 dehydrocholesterol pharmacophore molBLOCKS DHCR7; Smith Lemli Opitz Syndrome.

Medications having the unwanted side effect of inhibiting 7-dehydrocholesterol reductase (DHCR7), one of the last enzymes in the cholesterol biosynthesis pathway, account for about 300 million yearly prescriptions in the United States. Many of these drugs are currently prescribed to pregnant women. Many DHCR7-inhibiting medications share chem. similarities, which can be the active substructure responsible for the medication affinity to the enzyme. This work highlights a computational strategy to identify enriched fragments in a set of DHCR7-inhibiting medications. The computational approach used here involves systematic fragmentation of mols. using the molBLOCKS tool, followed by enrichment anal. The results of this approach highlight putative pharmacophores that might be responsible for the DHCR7-inhibiting activity of some of these medications. The identification of DHCR7-inhibiting substructures is an important step toward knowledge-based drug development and can improve the neurodevelopmental safety of medications.

ACS Pharmacology & Translational Science published new progress about Chemoinformatics. 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Quality Control of 434-16-2.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Lenormand, Anthony; Reyes Mendez, Lucia; Coulomb, Julien published the artcile< Relay-Heck Cross-Coupling Between Alkenyl Halides and Unsaturated Alcohols in the Synthesis of Open-Chain Analogues of Musk Odorant Vulcanolide>, HPLC of Formula: 627-27-0, the main research area is alkenyl halide alkenol palladium catalyst Heck cross coupling; carbonyl compound preparation; Heck reactions; alkenyl halides; palladium; relay; unsaturated alcohols.

Unactivated alkenyl iodides and bromides underwent an unprecedented palladium-catalyzed relay-Heck cross-coupling with a whole range of alkenols of different chain lengths linking the alkene and the alc., affording unsaturated aldehydes and ketones in moderate to good yields. In contrast, alkenyl triflates were not suitable partners for this reaction. This method allowed the preparation of open-chain analogs of the musk odorant Vulcanolide, several of which retained key olfactory properties of the parent mol.

Chemistry – A European Journal published new progress about Alkenyl alcohols Role: RCT (Reactant), RACT (Reactant or Reagent). 627-27-0 belongs to class alcohols-buliding-blocks, and the molecular formula is C4H8O, HPLC of Formula: 627-27-0.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts