Tag: M.W=250-300

Agbaje, Olorunsola F.; Coleman, Ruth L.; Hattersley, Andrew T.; Jones, Angus G.; Pearson, Ewan R.; Shields, Beverley M.; Holman, Rury R. published the artcile< Predicting post one-year durability of glucose-lowering monotherapies in patients with newly-diagnosed type 2 diabetes mellitus - A MASTERMIND precision medicine approach (UKPDS 87)>, Application In Synthesis of 94-20-2, the main research area is durability glucose monotherapy diabetes mellitus; Durability; Glucose-lowering agents; Modelling; Monotherapy failure; Precision medicine.

Predicting likely durability of glucose-lowering therapies for people with type 2 diabetes (T2D) could help inform individualised therapeutic choices. We used data from UKPDS patients with newly-diagnosed T2D randomised to first-line glucose-lowering monotherapy with chlorpropamide-glibenclamide-basal insulin or metformin. In 2339 participants who achieved one-year HbA1c values <7.5% (<59 mmol/mol)-we assessed relationships between one-year characteristics and time to monotherapy-failure (HbA1c ≥ 7.5% or requiring second-line therapy). Model validation was performed using bootstrap sampling.Follow-up was median (IQR) 11.0 (8.0-14.0) years. Monotherapy-failure occurred in 72%-82%-75% and 79% for those randomised to chlorpropamide-glibenclamide-basal insulin or metformin resp.-after median 4.5 (3.0-6.6)-3.7 (2.6-5.6)-4.2 (2.7-6.5) and 3.8 (2.6- 5.2) years. Time-to-monotherapy-failure was predicted primarily by HbA1c and BMI values-with other risk factors varying by type of monotherapy-with predictions to within ±2.5 years for 55%-60%-56% and 57% of the chlorpropamide-glibenclamide-basal insulin and metformin monotherapy cohorts resp. Post one-year glycemic durability can be predicted robustly in individuals with newly-diagnosed T2D who achieve HbA1c values < 7.5% one year after commencing traditional monotherapies. Such information could be used to help guide glycemic management for individual patients. Diabetes Research and Clinical Practice published new progress about Durability of materials. 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, Application In Synthesis of 94-20-2.

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

Singh, Imocha Rajkumar; Mitra, Sivaprasad published the artcile< Modulated Protein Binding Ability of Anti-Diabetic Drugs in Presence of Monodispersed Gold Nanoparticles and its Inhibitory Potential towards Advanced Glycated End (AGE) Product Formation>, SDS of cas: 94-20-2, the main research area is gold nanoparticle delivery advanced glycated end antidiabetic agent; AGE product; Drug binding; Fluorescence; Nanomedicine; Serum albumin.

Binding strength of the anti-diabetic drugs chlorpropamide (CPM) and tolbutamide (TBM) with model protein bovine serum albumin (BSA) shows strong modulation in presence of colloidal gold nanoparticles (AuNP). Intrinsic tryptophan fluorescence of both the native BSA and BSA-AuNP conjugate quenched in presence of the drugs. Stern-Volmer quenching constant (KSV) of CPM binding to BSA-AuNP conjugate at different temperatures is almost twice (6.76∼14.76 x 103 M-1) than the corresponding values in native BSA (3.21∼5.72 x 103 M-1). However, the calculated KSV values with TBM show certain degree of reduction in presence of AuNP (6.46x 103 M-1), while comparing with native BSA (8.83 x 103 M-1). The binding mode of CPM towards BSA-AuNP conjugate is mainly through hydrophobic forces; whereas, TBM binding is identified to be Van der Waal’s and hydrogen bonding type of interaction. Fluorescence lifetime anal. confirms static type of quenching for the intrinsic tryptophan fluorescence of BSA as well as BSA-AuNP conjugate with addition of CPM and TBM at different concentrations The α-helical content in the secondary structure of BSA is decreased to 48.32% and 45. 28% in presence of AuNP, when the concentration of CPM is 0.08 mM and 0.16 mM in comparison with that of native protein (50.13%). On the other hand, the intensity of sugar induced advanced glycated end (AGE) product fluorescence is decreased by 55% and 80% at 0.13 nM and 0.68 nM AuNP, resp. Change in the binding strength of the drugs with transport protein and reduced AGE product formation in presence of AuNP could lead to a major development in the field of nanomedicine and associated drug delivery techniques. Graphical AbstractModulated drug binding ability and AGE product formation of serum proteins in presence of AuNP [graphic not available: see fulltext].

Journal of Fluorescence published new progress about Adsorption. 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, SDS of cas: 94-20-2.

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

Park, Heejun; Nie, Haichen; Dhiman, Abhijeet; Tomar, Vikas; Zhou, Qi Tony published the artcile< Understanding Dynamics of Polymorphic Conversion during the Tableting Process Using In Situ Mechanical Raman Spectroscopy>, Computed Properties of 94-20-2, the main research area is chlorpropamide polymorphism interconversion tableting Raman spectroscopy tableting deformation; chlorpropamide; deformation; in situ mechanical Raman spectroscopy; polymorphic interconversion; tableting.

The objective of this study is to achieve a fundamental understanding of polymorphic interconversion during the tableting process, including during compaction, dwell, decompression/unloading, and ejection using an in situ mech. Raman spectroscopy. The fit-for-purpose in situ mech. Raman spectroscopy developed herein can provide simultaneous measurement of Raman spectra and densification for the powder compacts. Chlorpropamide (CPA), an antidiabetic drug, was selected as a model pharmaceutical compound because of its mech. shear-induced polymorphic conversions. The results confirm that CPA polymorph A (CPA-A) was transformed to CPA polymorph C (CPA-C) under different compaction stresses. We also observed that the converted polymorph CPA-C could be reverted to the CPA-A due to the elastic recovery of powder compacts as detected during dwelling and unloading. This study is the first depiction of the dynamics of CPA polymorphic interconversion during compression, dwell, unloading, and ejection. Mechanistically, this study illustrates a correlation between the change in the powder compact’s relative d. and polymorphic interconversion of the drug substance in different solid-state forms. The present research suggests that the process-induced polymorph conversion is a complicated dynamic process, which could be affected by the compaction pressure, the elasticity/plasticity of the material, the level of elastic recovery, and the dissipation of residual stress. In summary, this study demonstrates that the in situ mech. Raman spectroscopy approach enables the simultaneous detection of mech. and chem. information of the powder compact throughout the tableting process.

Molecular Pharmaceutics published new progress about Binary systems. 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, Computed Properties of 94-20-2.

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

Ahmad, Tanveer; Mehmood, Tariq; Shahid, Muhammad; Ahmad, Adnan; Basra, Muhammad Asim Raza; Zia-ur-Rehman, Muhammad; Munawar, Munawar Ali published the artcile< In vivo anti-diabetic studies of sulfonylurea-sulfonamide hybrids>, HPLC of Formula: 94-20-2, the main research area is antidiabetic sulfonylurea sulfonamide hybrid.

Owing to alarming increase of diabetes mellitus around the world, there is a need to discover new mols. to tackle with the problem. In this work, sulfonamides and sulfonylurea-sulfonamide hybrids were synthesized from simple mol. of 4-aminobenzenesulfonamide by its reaction with aryl sulfonyl chlorides. Anti-diabetic activities of these pharmacophores were studied by oral glucose tolerance test (OGTT) percentage anal. on Sprague Dawley (SD) rats at the dose of 20mg/kg using glibenclamide (GC). Among these synthesized pharmacophores, six compounds exhibited percentage reduction (20.47 ± 2.54 to 44.97 ± 2.16%) and (20.79 ± 1.55 to 37 ± 2.94%) in blood glucose level at 20mg/kg dose compared to glibenclamide (74 ± 3.10% reduction) 50mg/kg dose of glibenclamide after 2 and 5 h of oral administration resp. Present results showed that these compounds might be excellent addition in the drugs used to suppress the higher level of blood glucose level in diabetes mellitus.

Pakistan Journal of Zoology published new progress about Antidiabetic agents. 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

Dybeck, Eric C.; McMahon, David P.; Day, Graeme M.; Shirts, Michael R. published the artcile< Exploring the Multi-minima Behavior of Small Molecule Crystal Polymorphs at Finite Temperature>, Recommanded Product: 4-Chloro-N-(propylcarbamoyl)benzenesulfonamide, the main research area is crystal structure prediction polymorphism packing mol crystal polymorphs.

The predicted ambient-temperature crystal structures of organic small mols. are often represented by a single energy-minimized configuration at zero Kelvin. This procedure effectively collapses the ensemble of configurations that would be present at ambient temperature into a single representative structure. This simplification is likely to break down if the crystal structure has multiple different lattice-energy min. within the ambient temperature ensemble. In this paper, we explore the existence of multiple min. within finite-temperature crystal basins by sampling crystals at a range of temperatures followed by rapidly quenching the configurations. We then observe whether each crystal returns to the original min. or to an ensemble of min. on the lattice-energy landscape. Eight of the twelve compounds examined in this work have at least one polymorph with multi-min. behavior. These multi-min. basins have implications for crystal structure prediction studies, and it is therefore important to understand the factors that lead a crystal structure to have multiple min. We find that, in general, the existence of multiple min. within a crystal basin is more likely for the compounds that are larger and have more flexibility. We find that the number of min. found tends to increase with the sampling temperature, and the lattice energy of min. found from the same finite-temperature trajectory can vary by >2.0 kJ/mol. Finally, we show that the lattice energy min. contained within a single ambient temperature basin can have different space groups and numbers of mols. in the asym. unit. Overall, the data suggests that many exptl. crystal polymorphs are likely to have multi-min. behavior and are best described by an ensemble of structures encompassing many min. rather than by a single lattice-energy min.

Crystal Growth & Design published new progress about Configuration. 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, Recommanded Product: 4-Chloro-N-(propylcarbamoyl)benzenesulfonamide.

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

Fahim, Shahariar Mohammed; Hsu, Chiu-Hsieh; Lin, Fang-Ju; Qian, Jingjing; Chou, Chiahung published the artcile< Association between prior use of anti-diabetic medication and breast cancer stage at diagnosis>, Category: amides-buliding-blocks, the main research area is antidiabetic medication breast cancer association diagnosis; Breast cancer; diabetes; medicare beneficiaries; stage at diagnosis.

Knowledge regarding antidiabetic medication (ADM) use prior to breast cancer (BC) diagnosis remains limited. The objectives were to (1) evaluate if the prior use of ADM was associated with BC stage at diagnosis and (2) identify and compare patient characteristics among BC patients using different ADMs. Newly diagnosed female BC patients exposed to any medication during one year prior to cancer diagnosis were identified in 2008-2013 Linked Surveillance, Epidemiol., and End Results (SEER)-Medicare database. Stage at diagnosis, categorized as early and advanced, was the primary outcome. Chi-square tests were used to compare characteristics and logistic regression models were applied to examine the effect while controlling for patient’s characteristics. A total of 1,719 female BC patients used ADM while 6,084 patients were non-ADM users. Although a higher proportion of ADM users (20.36%) were diagnosed with advanced stage compared to the non-ADM users (14.46%), the difference was not statistically significant after adjusting for the patients’ characteristics. Besides, insulin users were more likely to be diagnosed with advanced stage (adjusted odds ratio 1.69; 95% CI 1.15, 2.48) compared to metformin users. The association between ADM use and BC diagnostic characteristics varied based on different treatments.

Expert Opinion on Drug Safety published new progress about Antidiabetic agents. 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, Category: amides-buliding-blocks.

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

Mao, Zhifan; Liu, Wenwen; Huang, Yunyuan; Sun, Tianyue; Bao, Keting; Feng, Jiali; Moskalev, Alexey; Hu, Zelan; Li, Jian published the artcile< Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species>, SDS of cas: 94-20-2, the main research area is chlorpropamide antiaging agent mitochondrial complex2 aging; ATP sensitive potassium channels; Anti-aging; Chlorpropamide; Mitochondrial complex II; Mitochondrial reactive oxygen species; Senescence; Succinate dehydrogenase; Sulfonylureas.

Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K+ (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans.

Acta Pharmaceutica Sinica B published new progress about Aging, animal. 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, SDS of cas: 94-20-2.

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

Vasconcelos, Ingrid; da Silva, Pedro Henrique Reis; Dias, Derick Rodrigues Davila; de Freitas Marques, Maria Betania; da Nova Mussel, Wagner; Pedrosa, Tercio Assuncao; Ribeiro e Silva, Maria Elisa Scarpelli; de Souza Freitas, Roberto Fernando; de Sousa, Ricardo Geraldo; Fernandes, Christian published the artcile< Synthesis and characterization of a molecularly imprinted polymer (MIP) for solid-phase extraction of the antidiabetic gliclazide from human plasma>, Computed Properties of 94-20-2, the main research area is gliclazide molecularly imprinted polymer solid phase extraction; Diabetes mellitus; Molecularly imprinted solid-phase extraction; Sample preparation; Sulfonylureas.

Gliclazide is a sulfonylurea frequently prescribed for the management of type 2 diabetes mellitus in elderly patients and for patients with chronic renal or hepatic diseases. Even though it is considered a safer alternative, the drug can provoke side effects in some patients, especially hypoglycemia, due to the high interindividual variability. Therefore, the quantification of gliclazide in biol. samples is usually recommended in order to assure efficacy and safety of the pharmacotherapy. However, due to the complexity of biol. matrixes, therapeutic monitoring can be very challenging, especially in the sample preparation step. Synthesis conditions were optimized (monomer, crosslinker and porogen) and the polymer was characterized for its morphol., physicochem. and stability properties. The influence of drug concentration, solvent composition and pH on the coefficient of distribution (Kd) and imprinting factor (IF) were studied, as well as repeatability between batches and selectivity. The best reaction yield, extraction capacity, and selectivity was obtained using 2-hydroxyethyl methacrylate (2-HEMA), ethyleneglycol dimethacrylate (EGDMA) and acetonitrile. The developed method by MISPE-HPLC-UV showed to be appropriate to determine gliclazide in human plasma samples.

Materials Science & Engineering, C: Materials for Biological Applications published new progress about Blood plasma. 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, Computed Properties of 94-20-2.

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

Sagandira, Cloudius R.; Watts, Paul published the artcile< Rapid Multigram-Scale End-to-End Continuous-Flow Synthesis of Sulfonylurea Antidiabetes Drugs: Gliclazide, Chlorpropamide, and Tolbutamide>, Related Products of 94-20-2, the main research area is chlorpropamide gliclazide tolbutamide continuous flow preparation antidiabetic agent.

A multigram-scale robust, efficient, and safe end-to-end continuous-flow process for the diabetes sulfonylurea drugs gliclazide, chlorpropamide, and tolbutamide is reported. The drugs were prepared by the treatment of an amine with a haloformate affording carbamate, which was subsequently treated with a sulfonamide to afford sulfonylurea. Gliclazide was obtained in 87% yield within 2.5 min total residence time with 26 g/h throughput; 0.2 kg of the drug was produced in 8 h of running the system continuously. Chlorpropamide and tolbutamide were both obtained in 94% yield within 1 min residence time with 184-188 g/h throughput; 1.4-1.5 kg of the drugs was produced in 8 h of running the system continuously. N-Substituted carbamates were used as safe alternatives to the hazardous isocyanates in constructing the sulfonyl urea moiety.

Synthesis published new progress about Antidiabetic agents. 94-20-2 belongs to class amides-buliding-blocks, and the molecular formula is C10H13ClN2O3S, Related Products of 94-20-2.

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

Tomaru, Atsuko; Toshimoto, Kota; Lee, Wooin; Ishigame, Keiko; Sugiyama, Yuichi published the artcile< A Simple Decision Tree Suited for Identification of Early Oral Drug Candidates With Likely Pharmacokinetic Nonlinearity by Intestinal CYP3A Saturation>, Product Details of C10H13ClN2O3S, the main research area is CYP3A pharmacokinetic Intestinal absorption type I nonlinearity; Cytochrome P450 (CYP) 3A; First-pass metabolism; Intestinal absorption; Nonlinear pharmacokinetics; Oral absorption.

To identify oral drugs that likely display nonlinear pharmacokinetics due to saturable metabolism by intestinal CYP3A, our previous report using CYP3A substrate drugs proposed an approach using thresholds for the linear index number (LIN3A = dose/Km; Km, Michaelis-Menten constant for CYP3A) and the intestinal availability (FaFg). Here, we aimed to extend the validity of the previous approach using both CYP3A substrate and non-substrate drugs and to devise a decision tree suited for early drug candidates using in vitro metabolic intrinsic clearance (CLint, vitro) instead of FaFg. Out of 152 oral drugs (including 136 drugs approved in Japan, US or both), type I nonlinearity (in which systemic drug exposure increases in a more than dose-proportional manner) was noted with 82 drugs (54%), among which 58 drugs were identified as CYP3A substrates based on public information. Based on practical feasibility, 41 drugs were selected from CYP3A substrates and subjected to inhouse metabolic assessment. The results were used to determine the thresholds for CLint, vitro (0.45μL/min/pmol CYP3A4) and LIN3A (1.0 L). For four drugs incorrectly predicted, potential mechanisms were looked up. Overall, our proposed decision tree may aid in the identification of early drug candidates with intestinal CYP3A-derived type I nonlinearity.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about Cytochrome P450 CYP3A inhibitors. 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