Author: Jessica.F

Chu, Junjun; Xing, Changsheng; Du, Yang; Duan, Tianhao; Liu, Siyao; Zhang, Pengfei; Cheng, Chumeng; Henley, Jill; Liu, Xin; Qian, Chen; Yin, Bingnan; Wang, Helen Yicheng; Wang, Rong-Fu published the artcile< Pharmacological inhibition of fatty acid synthesis blocks SARS-CoV-2 replication>, Reference of 96829-58-2, the main research area is pharmacol inhibition fatty acid synthesis replication SARSCoV2 COVID19.

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 is a virus-induced inflammatory disease of the airways and lungs that leads to severe multi-organ damage and death. Here we show that cellular lipid synthesis is required for SARS-CoV-2 replication and offers an opportunity for pharmacol. intervention. Screening a short-hairpin RNA sublibrary that targets metabolic genes, we identified genes that either inhibit or promote SARS-CoV-2 viral infection, including two key candidate genes, ACACA and FASN, which operate in the same lipid synthesis pathway. We further screened and identified several potent inhibitors of fatty acid synthase (encoded by FASN), including the US Food and Drug Administration-approved anti-obesity drug orlistat, and found that it inhibits in vitro replication of SARS-CoV-2 variants, including more contagious new variants, such as Delta. In a mouse model of SARS-CoV-2 infection (K18-hACE2 transgenic mice), injections of orlistat resulted in lower SARS-CoV-2 viral levels in the lung, reduced lung pathol. and increased mouse survival. Our findings identify fatty acid synthase inhibitors as drug candidates for the prevention and treatment of COVID-19 by inhibiting SARS-CoV-2 replication. Clin. trials are needed to evaluate the efficacy of repurposing fatty acid synthase inhibitors for severe COVID-19 in humans.

Nature Metabolism published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (FASN). 96829-58-2 belongs to class amides-buliding-blocks, and the molecular formula is C29H53NO5, Reference of 96829-58-2.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Kaniskan, Nevin; Kokten, Sule; Celik, Ilhami published the artcile< A new protocol for the synthesis of primary, secondary and tertiary anthranilamides utilizing N-(2-aminoarylacyl)benzotriazoles>, Application In Synthesis of 5004-88-6, the main research area is anthranilamide production benzotriazole intermediate.

A convenient route for efficient conversion of unprotected anthranilic acids into the corresponding N-(2-aminoarylacyl)benzotriazoles is described. N-(2-Aminoarylacyl)benzotriazoles have been successfully used to synthesize primary, secondary, and tertiary anthranilamides in high yields (71-96%).

ARKIVOC (Gainesville, FL, United States) published new progress about Aromatic amides Role: SPN (Synthetic Preparation), PREP (Preparation). 5004-88-6 belongs to class amides-buliding-blocks, and the molecular formula is C9H12N2O3, Application In Synthesis of 5004-88-6.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Tan, Xi; Yang, Lingfeng; Khunti, Kamlesh; Zhang, Ruya; Zhang, Ye; Rajpathak, Swapnil; Yu, Miao published the artcile< Factors associated with switching from sulphonylureas to dipeptidyl peptidase 4 inhibitors among patients with type 2 diabetes in the United States>, Formula: C10H13ClN2O3S, the main research area is sulfonylurea dipeptidyl peptidase diabetes united states; DPP-4 inhibitor; cohort study; database research; observational study; sulphonylureas; type 2 diabetes.

Studies examining the prevalence of and factors associated with switching from sulfonylureas (SUs) to dipeptidyl peptidase 4 (DPP-4) inhibitors in real-world settings are lacking. We assessed the factors associated with switching from SUs to DPP-4 inhibitors in the United States. This retrospective cohort study was conducted using the Optum Clinformatics Data Mart (2009-2018). Adults with type 2 diabetes and newly prescribed at least two SUs were included and were followed for 2 years after the initiation of SU (index date). We compared the characteristics of those who switched from SUs to DPP-4 inhibitors (only; no addnl. antidiabetic drugs) with those who continued with SUs (without adding other antidiabetic drugs) using multivariate logistic regression. Multinomial regression analyses were also conducted to assess the factors associated with switching to different drug classes vs. continuation with SUs. In a sample of 119 107 new SU users, 2.2% (2633) switched to DPP-4 inhibitors, 3.8% (4542) switched to antidiabetic drugs other than DPP-4 inhibitors, 68.3% (81 394) discontinued SUs but did not switch to another antidiabetic drug, 12.9% (15 345) continued with SUs and added other antidiabetic drugs, and 12.8% (15 193) continued with SUs only. Multivariate logistic regression showed that those who had significantly higher likelihood of switching were younger, female [vs. males; adjusted odds ratio (AOR) = 0.70], and living in the south; had previous use of DPP-4 inhibitors (AOR = 1.71); were not using antidiabetic drugs at baseline; had more baseline diabetes-related emergency room visits (AOR = 1.13), depression (AOR = 1.34), post-index hypoglycemia (AOR = 2.20), and an earlier index year; and were glyburide users (vs. glimepiride users; AOR = 1.29). The discontinuation rate for SUs is high. Factors associated with switching from SUs to DPP-4 inhibitors included age, sex, geog. region, baseline antidiabetic drug use, type of SU, baseline diabetes-related emergency room visits, hypoglycemia and depression.

Diabetes, Obesity and Metabolism published new progress about Antidiabetic agents. 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, Formula: C10H13ClN2O3S.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Kikelj, D. published the artcile< Product class 13: quinazolines>, Electric Literature of 112253-70-0, the main research area is review quinazoline preparation; ring closure transformation quinazoline preparation review; aromatization quinazoline preparation review; substituent modification quinazoline preparation review.

A review. Preparation of quinazolines by ring closure and ring transformation reactions as well as aromatization and substituent modification is given.

Science of Synthesis published new progress about 112253-70-0. 112253-70-0 belongs to class amides-buliding-blocks, and the molecular formula is C7H7BrN2O, Electric Literature of 112253-70-0.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Mishra, Rashmi; Sehring, Ivonne; Cederlund, Maria; Mulaw, Medhanie; Weidinger, Gilbert published the artcile< NF-κB Signaling Negatively Regulates Osteoblast Dedifferentiation during Zebrafish Bone Regeneration>, COA of Formula: C10H13ClN2O3S, the main research area is Danio osteoblast dedifferentiation bone regeneration; NF-kappaB; bglap; bone; dedifferentiation; fin; osteoblast; osteocalcin; plasticity; regeneration; zebrafish.

Dedifferentiation of mature cells is an intriguing cellular process associated with regeneration of several organs. During zebrafish fin regeneration, osteoblasts dedifferentiate to osteogenic progenitors that provide source cells for bone restoration. We performed a high-content in vivo chem. screen for regulators of osteoblast dedifferentiation and fin regenerative growth. NF-κB signaling emerged as a specific regulator of dedifferentiation. The pathway is active in mature osteoblasts and downregulated prior to dedifferentiation. Pathway activation blocked osteoblast dedifferentiation, while NF-κB signaling inhibition enhanced dedifferentiation. Conditional Cre-lox-mediated NF-κB signaling manipulation specifically in osteoblasts showed that the pathway acts cell autonomously to interfere with osteoblast dedifferentiation. NF-κB signaling acts upstream of retinoic acid (RA) signaling, which also needs to be downregulated for dedifferentiation to occur, via suppression of the RA-degrading enzyme cyp26b1. Our findings shed light on the mol. regulation of regenerative cellular plasticity.

Developmental Cell published new progress about Biochemistry. 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, COA of Formula: C10H13ClN2O3S.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Guimaraes, Cristiano R. W. published the artcile< A Direct Comparison of the MM-GB/SA Scoring Procedure and Free-Energy Perturbation Calculations Using Carbonic Anhydrase as a Test Case: Strengths and Pitfalls of Each Approach>, Application of C6H6FNO2S, the main research area is MM GB SA scoring free energy perturbation carbonic anhydrase.

MM-GB/SA scoring and free energy perturbation (FEP) calculations have emerged as reliable methodologies to understand structural and energetic relationships to binding. In spite of successful applications to elucidate the structure-activity relationships for few pairs of ligands, the reality is that the performance of FEP calculations has rarely been tested for more than a handful of compounds In this work, a series of 13 benzene sulfonamide inhibitors of carbonic anhydrase with binding free energies determined by isothermal titration calorimetry was selected as a test case. R2 values of 0.70, 0.71, and 0.49 with the experiment were obtained with MM-GB/SA and FEP simulations run with MCPRO+ and Desmond, resp. All methods work well, but the results obtained with Desmond are inferior to MM-GB/SA and MCPRO+. The main contrast between the methods is the level of sampling, ranging from full to restricted flexibility to single conformation for the complexes in Desmond, MCPRO+, and MM-GB/SA, resp. The current and historical results obtained with MM-GB/SA qualify this approach as a more attractive alternative for rank-ordering; it can achieve equivalent or superior predictive accuracy and handle more structurally dissimilar ligands at a fraction of the computational cost of the rigorous free-energy methods. As for the large theor. dynamic range for the binding energies, that seems to be a direct result of the degree of sampling in the simulations since MCPRO+ as well as MM-GB/SA are plagued by this. Van’t Hoff anal. for selected pairs of ligands suggests that the wider scoring spread is not only affected by missing entropic contributions due to restricted sampling but also exaggerated enthalpic separation between the weak and potent compounds caused by diminished shielding of electrostatic interactions, thermal effects, and protein relaxation/strain.

Journal of Chemical Theory and Computation published new progress about Affinity. 1524-40-9 belongs to class amides-buliding-blocks, and the molecular formula is C6H6FNO2S, Application of C6H6FNO2S.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Yoo, Euna; Schulze, Christopher J.; Stokes, Barbara H.; Onguka, Ouma; Yeo, Tomas; Mok, Sachel; Gnadig, Nina F.; Zhou, Yani; Kurita, Kenji; Foe, Ian T.; Terrell, Stephanie M.; Boucher, Michael J.; Cieplak, Piotr; Kumpornsin, Krittikorn; Lee, Marcus C. S.; Linington, Roger G.; Long, Jonathan Z.; Uhlemann, Anne-Catrin; Weerapana, Eranthie; Fidock, David A.; Bogyo, Matthew published the artcile< The Antimalarial Natural Product Salinipostin A Identifies Essential α/β Serine Hydrolases Involved in Lipid Metabolism in P. falciparum Parasites>, Application In Synthesis of 96829-58-2, the main research area is Plasmodium falciparum; Salinipostin A; activity-based probes; chemical proteomics; lipid metabolism; malaria; natural products; serine hydrolases.

Salinipostin A (Sal A) is a potent antiplasmodial marine natural product with an undefined mechanism of action. Using a Sal A-derived activity-based probe, we identify its targets in the Plasmodium falciparum parasite. All of the identified proteins contain α/β serine hydrolase domains and several are essential for parasite growth. One of the essential targets displays a high degree of homol. to human monoacylglycerol lipase (MAGL) and is able to process lipid esters including a MAGL acylglyceride substrate. This Sal A target is inhibited by the anti-obesity drug Orlistat, which disrupts lipid metabolism Resistance selections yielded parasites that showed only minor reductions in sensitivity and that acquired mutations in a PRELI domain-containing protein linked to drug resistance in Toxoplasma gondii. This inability to evolve efficient resistance mechanisms combined with the non-essentiality of human homologs makes the serine hydrolases identified here promising antimalarial targets.

Cell Chemical Biology published new progress about 96829-58-2. 96829-58-2 belongs to class amides-buliding-blocks, and the molecular formula is C29H53NO5, Application In Synthesis of 96829-58-2.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Roberts, Bryan; Liptrot, David; Alcaraz, Lilian published the artcile< Novel Aryl and Heteroaryl Acyl Sulfamide Synthesis via Microwave-Assisted Palladium-Catalyzed Carbonylation>, Recommanded Product: Morpholine-4-sulfonamide, the main research area is aryl heteroaryl halide sulfamide nucleophile palladium carbonylation microwave irradiation; heteroaryl aryl acyl sulfamide preparation; carbonylation catalyst palladium.

A novel, simple synthesis of aryl and heteroaryl acyl sulfamides has been developed via palladium-catalyzed carbonylation of aryl or heteroaryl halides in the presence of sulfamide nucleophiles. A range of reactions illustrating the wide scope of this reaction was carried out under microwave irradiation in a vessel equipped with a gas inlet adapter and proceeded in good to excellent yields.

Organic Letters published new progress about Aryl halides Role: RCT (Reactant), RACT (Reactant or Reagent). 25999-04-6 belongs to class amides-buliding-blocks, and the molecular formula is C4H10N2O3S, Recommanded Product: Morpholine-4-sulfonamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Kerdphon, Sutthichat; Sanghong, Patthadon; Chatwichien, Jaruwan; Choommongkol, Vachira; Rithchumpon, Puracheth; Singh, Thishana; Meepowpan, Puttinan published the artcile< Commercial Copper-Catalyzed Aerobic Oxidative Synthesis of Quinazolinones from 2-Aminobenzamide and Methanol>, Computed Properties of 5004-88-6, the main research area is quinazolinone preparation copper catalyst aerobic oxidation aminobenzamide methanol.

The focus of this study was the development of a new synthetic method for quinazolinones based on the principles of Green Chem. Quinazolinones were synthesized from 2-aminobenzamide using methanol as both the C1 source and a green solvent in the presence of base Cs2CO3. Addnl., a com. available, economical copper complex was used as a catalyst in the reaction. The desired products were achieved in moderate to high yield with up to 99% isolated yield.

European Journal of Organic Chemistry published new progress about Benzamides Role: RCT (Reactant), RACT (Reactant or Reagent) (2-Aminobenzamide). 5004-88-6 belongs to class amides-buliding-blocks, and the molecular formula is C9H12N2O3, Computed Properties of 5004-88-6.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Thakral, Naveen K.; Thakral, Seema; Stephenson, Gregory A.; Sedlock, Robert; Suryanarayanan, Raj published the artcile< Compression-Induced Polymorphic Transformation in Tablets: Role of Shear Stress and Development of Mitigation Strategies>, Application of C10H13ClN2O3S, the main research area is Compression polymorphic transformation tablets shear stress; hydrostatic pressure; phase transformation; shear stress; tablet; viscoelastic excipients.

Our goals were to evaluate the effects of (i) hydrostatic pressure alone and (ii) its combined effect with shear stress during compaction, on the polymorphic transformation (form C → A) of a model drug, chlorpropamide. The powder was either subjected to hydrostatic pressure in a pressure vessel or compressed in a tablet press, at pressures ranging from 25 to 150 MPa. The overall extent of phase transformation was determined by powder X-ray diffractometry, whereas 2D-X-ray diffractometry enabled quantification of the spatial distribution of phase composition in tablets. Irresp. of the pressure, the extent of transformation following compaction was higher than that because of hydrostatic pressure alone, the difference attributed to the contribution of shear stress experienced during compaction. At a compression pressure of 25 MPa, there was a pronounced gradient in the extent of phase transformation when monitored from radial tablet surface to core. This gradient decreased with increase in compression pressure. Four approaches were attempted to minimize the effect of compression-induced phase transformation: (a) site-specific lubrication, (b) use of a viscoelastic excipient, (c) ceramic-lined die, and (d) use of cavity tablet. The ceramic-lined die coupled with site-specific lubrication was most effective in minimizing the extent of compression-induced phase transformation.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about Compression. 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, Application of C10H13ClN2O3S.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics