Author: Jessica.F

Podtelezhnikov, Alexei A.; Monroe, James J.; Aslamkhan, Amy G.; Pearson, Kara; Qin, Chunhua; Tamburino, Alex M.; Loboda, Andrey P.; Glaab, Warren E.; Sistare, Frank D.; Tanis, Keith Q. published the artcile< Quantitative transcriptional biomarkers of xenobiotic receptor activation in rat liver for the early assessment of drug safety liabilities>, Product Details of C10H13ClN2O3S, the main research area is transcriptional biomarker xenobiotic receptor rat liver drug toxicity safety; biomarkers; gene expression/regulation; liver; methods; receptor; safety evaluation; systems; toxicogenomics; toxicology; transcription factors.

The robust transcriptional plasticity of liver mediated through xenobiotic receptors underlies its ability to respond rapidly and effectively to diverse chem. stressors. Thus, drug-induced gene expression changes in liver serve not only as biomarkers of liver injury, but also as mechanistic sentinels of adaptation in metabolism, detoxification, and tissue protection from chems. Modern RNA sequencing methods offer an unmatched opportunity to quant. monitor these processes in parallel and to contextualize the spectrum of dose-dependent stress, adaptation, protection, and injury responses induced in liver by drug treatments. Using this approach, we profiled the transcriptional changes in rat liver following daily oral administration of 120 different compounds, many of which are known to be associated with clin. risk for drug-induced liver injury by diverse mechanisms. Clustering, correlation, and linear modeling analyses were used to identify and optimize coexpressed gene signatures modulated by drug treatment. Here, we specifically focused on prioritizing 9 key signatures for their pragmatic utility for routine monitoring in initial rat tolerability studies just prior to entering drug development. These signatures are associated with 5 canonical xenobiotic nuclear receptors (AHR, CAR, PXR, PPARα, ER), 3 mediators of reactive metabolite-mediated stress responses (NRF2, NRF1, P53), and 1 liver response following activation of the innate immune response. Comparing paradigm chem. inducers of each receptor to the other compounds surveyed enabled us to identify sets of optimized gene expression panels and associated scoring algorithms proposed as quant. mechanistic biomarkers with high sensitivity, specificity, and quant. accuracy. These findings were further qualified using public datasets, Open TG-GATEs and DrugMatrix, and internal development compounds With broader collaboration and addnl. qualification, the quant. toxicogenomic framework described here could inform candidate selection prior to committing to drug development, as well as complement and provide a deeper understanding of the conventional toxicol. study endpoints used later in drug development.

Toxicological Sciences published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (CAR). 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, Product Details of C10H13ClN2O3S.

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

B, Haripriya; Hasija, Avantika; Cruz-Cabeza, Aurora J.; Shruti, Ipsha; Chopra, Deepak published the artcile< Multicomponent Crystals of Chlorpropamide: Multiple Conformers, Multiple Z', and Proton Transfer at Play>, HPLC of Formula: 94-20-2, the main research area is multicomponent crystal chlorpropamide multiple conformer crystallog.

A new organic salt and a cocrystal of the antidiabetic drug chlorpropamide (cpa) were obtained by mechanochem. liquid-assisted grinding (LAG) with several cocrystal formers. An organic salt was formed with 4-(dimethylamino)pyridine (cpa:DMAP) and a cocrystal was obtained with 4,4′-dipyridyl (cpa:BP). After extensive screening for polymorphism/stoichiomorphism, two polymorphs of the cpa:DMAP salt (Forms I and II) and one form of the cocrystal cpa:BP were discovered. cpa:DMAP-I crystallized with eight mols. in the asym. unit (Z’ = 4, Z” = 8), whereas cpa:DMAP-II crystallized with two mols. in the asym. unit (Z’ = 1, Z” = 2). The new forms were characterized via single-crystal X-ray diffraction and powder X-ray diffraction along with thermal methods of characterization. Addnl., the various conformers found in these multicomponent forms are analyzed and compared to the known polymorphs of cpa. Finally, we show that the stable polymorph of the salt cpa:DMAP-I has a drastically enhanced aqueous solubility and dissolution rate relative to the pure cpa, thus giving it an advantage for improved drug delivery.

Crystal Growth & Design published new progress about Cocrystallization. 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, HPLC of Formula: 94-20-2.

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

Bisset, Alexander A.; Shiibashi, Akira; Desmond, Jasmine L.; Dishington, Allan; Jones, Teyrnon; Clarkson, Guy J.; Ikariya, Takao; Wills, Martin published the artcile< Synthesis and asymmetric hydrogenation of (3E)-1-benzyl-3-[(2-oxopyridin-1(2H)-yl)methylidene]piperidine-2,6-dione>, Quality Control of 1192620-83-9, the main research area is rhodium catalyst asym hydrogenation piperidinedione oxopyridinylmethylidene.

The synthesis of (3E)-1-benzyl-3-[(2-oxopyridin-1(2H)-yl)methylidene]piperidine-2,6-dione (I) from N-benzylglutarimide was achieved in three steps. The asym. hydrogenation of I gave either the product of partial reduction or full reduction, depending on the catalyst employed, with high ee in each case. Attempts at asym. transfer hydrogenation (ATH) of I resulted in formation of a racemic product.

Chemical Communications (Cambridge, United Kingdom) published new progress about Enantioselective synthesis. 1192620-83-9 belongs to class amides-buliding-blocks, and the molecular formula is C30H31ClN2O2RuS, Quality Control of 1192620-83-9.

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

Ravindranathan, Krishna; Tirado-Rives, Julian; Jorgensen, William L.; Guimaraes, Cristiano R. W. published the artcile< Improving MM-GB/SA Scoring through the Application of the Variable Dielectric Model>, Synthetic Route of 1524-40-9, the main research area is dielec constant scoring model protein ligand electrostatics; CDK2 Factor Xa p38 PDE10A carbonic anhydrase drug target.

A variable dielec. model based on residue types for better description of protein-ligand electrostatics in MM-GBSA scoring is reported. The variable dielec. approach provides better correlation with binding data and reduces the score dynamic range, typically observed in the standard MM-GB/SA method. The latter supports the view that exaggerated enthalpic separation between weak and potent compounds due to the lack of shielding effects in the model is greatly responsible for the wide scoring spread.

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

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

Murshed, Mubtasim; Pham, Anna; Vithani, Kapilkumar; Salim, Malinda; Boyd, Ben J. published the artcile< Controlling drug release by introducing lipase inhibitor within a lipid formulation>, HPLC of Formula: 96829-58-2, the main research area is Controlled-release; Drug overdose prevention; In vitro lipolysis; Lipase inhibitor; Lipid-based drug delivery systems (LBDDS); Oral formulation.

Drug overdose connected to marketed pharmaceutical products, particularly opioids, occurs at an alarming rate. Novel strategies through innovative formulation approaches that reduce the likelihood of overdose while allowing safe therapeutic outcomes are urgently required. The current study provides a proof-of-concept for a new formulation approach by co-formulating drug with a lipase inhibitor within a solid lipid formulation in order to prevent or reduce the harmful effects of taking multiple doses of an oral solid dose form. Lipase inhibitor controlled-release (LICR) formulations were created using a simple hot melt method to co-formulate the inhibitor (orlistat) and ibuprofen, as the model drug, within the lipid matrix. The digestion and drug release kinetics were determined using an in vitro lipolysis model. Above a threshold level of orlistat there was decreased digestibility of multiple doses of the LICR formulations, leading to reduced drug release. Upon administration of the formulations in capsules to rats, the LICR formulation displayed the lowest exposure of ibuprofen during the pharmacokinetic studies. This novel formulation approach shows promise in preventing accidental drug overdose after oral administration of multiple doses of formulation.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about 96829-58-2. 96829-58-2 belongs to class amides-buliding-blocks, and the molecular formula is C29H53NO5, HPLC of Formula: 96829-58-2.

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

Diaper, C. M. published the artcile< Other tetrahetero-substituted methanes>, COA of Formula: C9H12N2O3, the main research area is review hetero methane derivative preparation organic synthesis.

A review of the preparation and synthetic applications of tetrahetero-substituted methanes.

Science of Synthesis published new progress about 5004-88-6. 5004-88-6 belongs to class amides-buliding-blocks, and the molecular formula is C9H12N2O3, COA of Formula: C9H12N2O3.

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

Banerjee, Abhisek; Pawar, Mahesh Y.; Patil, Sandip; Yadav, Pravin S.; Kadam, Pradip A.; Kattige, Vidya G.; Deshpande, Durga S.; Pednekar, Pallavi V.; Pisat, Monali K.; Gharat, Laxmikant A. published the artcile< Development of 2-aryl substituted quinazolin-4(3H)-one, pyrido[4,3-d]pyrimidin-4(3H)-one and pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as microsomal prostaglandin E2 synthase-1 inhibitors>, Recommanded Product: 2-Amino-4-bromobenzamide, the main research area is quinazolinone preparation microsomal prostaglandin PGE2 synthase inhibitor NSAID analgesic; pyridopyrimidinone preparation microsomal prostaglandin PGE2 synthase inhibitor NSAID analgesic; Analgesic; Cyclooxygenase; Prostaglandin E(2); Quinazolinone; mPGES-1.

MPGES-1 is inducible terminal synthase acting downstream of COX enzymes in arachidonic acid pathway, regulates the biosynthesis of pro-inflammatory prostaglandin PGE2. Cardiovascular side effect of coxibs and NSAIDs, selective for COX-2 inhibition, stimulated interest in mPGES-1, a therapeutic target with potential to deliver safe and effective anti-inflammatory drugs. The synthesis and structure activity relationship of a series of compounds from 2-aryl substituted quinazolin-4(3H)-one, pyrido[4,3-d]pyrimidin-4(3H)-one and pyrido[2,3-d]pyrimidin-4(3H)-one scaffolds as mPGES-1 inhibitor are discussed. A set of three analogs were identified with <10 nM potencies in the recombinant human mPGES-1 enzyme and in the A549 cellular assays. These analogs were also found to be potent in the human whole blood assay (<400 nM). Furthermore, the representative compound I was shown to be selective with other prostanoid synthases and was able to effectively regulate PGE2 biosynthesis in clin. relevant inflammatory settings, in comparison with celecoxib. Bioorganic & Medicinal Chemistry Letters published new progress about Analgesics. 112253-70-0 belongs to class amides-buliding-blocks, and the molecular formula is C7H7BrN2O, Recommanded Product: 2-Amino-4-bromobenzamide.

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

Sharma, Deepak K.; Adams, Spencer T.; Liebmann, Kate L.; Choi, Adam; Miller, Stephen C. published the artcile< Sulfonamides Are an Overlooked Class of Electron Donors in Luminogenic Luciferins and Fluorescent Dyes>, Formula: C6H6ClNO2S, the main research area is sulfonamide firefly luciferase bioluminescence fluorescent dye.

Many fluorophores, and all bright light-emitting substrates for firefly luciferase, contain hydroxyl or amine electron donors. Sulfonamides were found to be capable of serving as replacements for these canonical groups. Unlike “”caged”” carboxamides, sulfonamide donors enable bioluminescence, and sulfonamidyl luciferins, coumarins, rhodols, and rhodamines are fluorescent in water.

Organic Letters published new progress about Absorptivity. 6961-82-6 belongs to class amides-buliding-blocks, and the molecular formula is C6H6ClNO2S, Formula: C6H6ClNO2S.

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

Liu, Zhen; Zhang, Yan-Shun; Wei, Yin; Shi, Min published the artcile< Metal-Free Synthesis of Polysubstituted Imidazolinone Through Cyclization of Amidines with 2-Substituted Acrylates>, COA of Formula: C6H6ClNO2S, the main research area is imidazolinone preparation; nucleophilic cyclization benzamidine sulfonylaminoacrylate.

Imidazolidinones such as I (R = 4-MeC6H4, 4-EtC6H4, 4-t-BuC6H4, 4-MeOC6H4, Ph, 4-O2NC6H4, 2-O2NC6H4, 4-FC6H4, 2-ClC6H4, 4-BrC6H4) were prepared by nucleophilic cyclization reaction of (sulfonylamino)acrylates H2CC(NHSO2R)CO2R1 (R = 4-MeC6H4, 4-EtC6H4, 4-t-BuC6H4, 4-MeOC6H4, Ph, 4-O2NC6H4, 2-O2NC6H4, 4-FC6H4, 2-ClC6H4, 4-BrC6H4; R1 = Me, Et, Ph, PhCH2) with benzamidines such as N-phenylbenzamidine in 1,2-dichloroethane at ambient temperature

European Journal of Organic Chemistry published new progress about Benzamidines Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 6961-82-6 belongs to class amides-buliding-blocks, and the molecular formula is C6H6ClNO2S, COA of Formula: C6H6ClNO2S.

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

Braeckmans, Marlies; Brouwers, Joachim; Mols, Raf; Servais, Cecile; Tack, Jan; Augustijns, Patrick published the artcile< Orlistat disposition in the human jejunum and the effect of lipolysis inhibition on bile salt concentrations and composition>, Application In Synthesis of 96829-58-2, the main research area is Bile salts; Fed state; Fenofibrate; Intestinal drug absorption; Jejunum; Orlistat.

The lipolysis-mediated postprandial small intestinal environment is known to influence the solubilisation and subsequent absorption of lipophilic drugs. In a previously performed small-scale clin. study in healthy volunteers, co-administration of the lipase inhibitor orlistat increased jejunal solubilisation and systemic absorption of fenofibrate after intake of the lipid-based formulation Fenogal. In the present study, the jejunal disposition of the locally acting orlistat was assessed and linked to fenofibrate solubilisation. In addition, the effect of orlistat-induced lipolysis inhibition on bile salt concentrations and composition was evaluated. Orlistat was distributed predominantly in the lipid layer, as indicated by a 5- to 14-fold higher AUC0-320 min in the total jejunal samples as compared to the micellar layers. No effect of orally administered orlistat on bile salt composition or total concentrations (ranging from 1.5 to 24.8 mM and 1.8 to 33.2 mM with and without orlistat co-administration, resp.) could be observed The intraluminal presence of orlistat in the total jejunal samples correlated with the increased fenofibrate solubilisation in the jejunum (r = 0.9344) and enhanced absorption (r = 0.8184), highlighting the importance of the intraluminal lipid phase in lipophilic drug absorption.

International Journal of Pharmaceutics (Amsterdam, Netherlands) 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