Tag: M.W=200-250

Stauffer, Kenneth J.; Williams, Peter D.; Selnick, Harold G.; Nantermet, Philippe G.; Newton, Christina L.; Homnick, Carl F.; Zrada, Matthew M.; Lewis, S. Dale; Lucas, Bobby J.; Krueger, Julie A.; Pietrak, Beth L.; Lyle, Elizabeth A.; Singh, Rominder; Miller-Stein, Cynthia; White, Rebecca B.; Wong, Bradley; Wallace, Audrey A.; Sitko, Gary R.; Cook, Jacquelyn J.; Holahan, Marie A.; Stranieri-Michener, Maria; Leonard, Yvonne M.; Lynch, Joseph J. Jr.; McMasters, Daniel R.; Yan, Youwei published the artcile< 9-Hydroxyazafluorenes and Their Use in Thrombin Inhibitors>, Category: pyridine-derivatives, the main research area is hydroxyazafluorene derivative preparation thrombin inhibitor anticoagulant thrombosis crystal structure.

Optimization of a previously reported thrombin inhibitor, 9-hydroxy-9-fluorenylcarbonyl-L-prolyl-trans-4-aminocyclohexylmethylamide (1), by replacing the aminocyclohexyl P1 group provided a new lead structure, 9-hydroxy-9-fluorenylcarbonyl-L-prolyl-2-aminomethyl-5-chlorobenzylamide (2), with improved potency (Ki = 0.49 nM for human thrombin, 2× APTT = 0.37 μM in human plasma) and pharmacokinetic properties (F = 39%, iv T1/2 = 13 h in dogs). An effective strategy for reducing plasma protein binding of 2 and improving efficacy in an in vivo thrombosis model in rats was to replace the lipophilic fluorenyl group in P3 with an azafluorenyl group. Systematic investigation of all possible azafluorenyl P3 isomers and azafluorenyl-N-oxide analogs of 2 led to the identification of an optimal compound, 3-aza-9-hydroxyfluoren-9(R)-ylcarbonyl-L-prolyl-2-aminomethyl-5-chlorobenzylamide (I), with high potency (Ki = 0.40 nM, 2× APTT = 0.18 μM), excellent pharmacokinetic properties (F = 55%, T1/2 = 14 h in dogs), and complete efficacy in the in vivo thrombosis model in rats (inhibition of FeCl3-induced vessel occlusions in six of six rats receiving an i.v. infusion of 10 μg/kg/min of I). The stereochem. of the azafluorenyl group in I was determined by x-ray crystallog. anal. of its N-oxide derivative bound in the active site of human thrombin.

Journal of Medicinal Chemistry published new progress about Anticoagulants. 53636-56-9 belongs to class pyridine-derivatives, and the molecular formula is C7H6BrNO2, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Wang, Dan-Yang; Si, Yubing; Guo, Wei; Fu, Yongzhu published the artcile< Long Cycle Life Organic Polysulfide Catholyte for Rechargeable Lithium Batteries>, SDS of cas: 2127-03-9, the main research area is rechargeable lithium battery organic polysulfide catholyte; dipyridyl polysulfide; lithium batteries; molecular dynamic simulations; organosulfide; ultra performance liquid chromatographyquadrupole time‐of‐flight‐mass spectrometry (UPLC‐QTof‐MS).

Herein, a spectrum of dipyridyl polysulfides (Py2Sx, 3 ≤ x ≤ 8) is prepared in electrolyte by a one-pot synthesis method from dipyridyl disulfide (Py2S2) and elemental sulfur. It renders up to seven dipyridyl polysulfides (i.e., Py2S3, Py2S4, Py2S5, Py2S6, Py2S7, and Py2S8) which show fully reversible electrochem. behavior in lithium batteries. In the discharge, the initial lithiation occurs at 2.45 V leading to the breakage of Sα-Sβ bonds in Py2Sx and formation of lithium 2-pyridinethiolate, in which lithium is coordinated in between N and S atoms. The left sulfur species act as elemental sulfur, showing two voltage plateaus at 2.3 and 2.1 V. The mol. dynamics simulations show the attraction between pyridyl groups and lithium polysulfides/sulfide via N···Li···S bonds, which enable good retention of soluble discharge products within electrodes and stable cycling performance. In the recharge, low-order Py2Sx (e.g., Py2S3, Py2S4, and Py2S5) remain as the charged products. The mixture catholyte exhibits superlong cycle life at 1C rate with 1200 cycles and 70.5% capacity retention.

Advanced Science (Weinheim, Germany) published new progress about Aqueous solutions, electrolyzed water. 2127-03-9 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2S2, SDS of cas: 2127-03-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Conde, Nerea; SanMartin, Raul; Herrero, Maria Teresa; Dominguez, Esther published the artcile< Palladium NNC Pincer Complex as an Efficient Catalyst for the Cycloisomerization of Alkynoic Acids>, Product Details of C7H6BrNO2, the main research area is alkynoic acid cycloisomerization palladium NNC pincer complex catalyst.

A two-step (nucleophilic substitution/palladation by oxidative addition) sequence provides a high-yielding access to a non-sym. palladium NNC pincer complex. A number of terminal and internal alkynoic acids with different substitution patterns at the α- and β-positions are regio- and diastereoselectively cycloisomerized to the corresponding exocyclic enol lactones in the presence of exceedingly low amounts of the latter palladium complex, so that unprecedented turnover numbers and frequencies ranging from 1000,000 to 700,000 and from 41,667 to 9722 h-1, resp., are achieved. The optimized protocol, based on the use of a catalytic amount of triethylamine as base, allows an easy real-time monitoring of the reaction by NMR spectroscopy. Several pieces of evidence in favor of the direct participation of the above pincer complex as the catalyst of the reaction were gathered from kinetic and poisoning experiments

Advanced Synthesis & Catalysis published new progress about Carboxylic acids, alkynyl Role: RCT (Reactant), RACT (Reactant or Reagent). 53636-56-9 belongs to class pyridine-derivatives, and the molecular formula is C7H6BrNO2, Product Details of C7H6BrNO2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Mangala Prasad, Vidya; Leaman, Daniel P.; Lovendahl, Klaus N.; Croft, Jacob T.; Benhaim, Mark A.; Hodge, Edgar A.; Zwick, Michael B.; Lee, Kelly K. published the artcile< Cryo-ET of Env on intact HIV virions reveals structural variation and positioning on the Gag lattice>, Computed Properties of 2127-03-9, the main research area is HIV1 virions structural variation Env Gag glycosylation gp120; Gag-Env interaction; HIV Env glycoprotein; HIV assembly; broadly neutralizing antibody; cryo-electron microscopy; cryo-electron tomography; hydrogen/deuterium-exchange mass spectrometry; sub-tomogram averaging; vaccine design; virus structure.

HIV-1 Env mediates viral entry into host cells and is the sole target for neutralizing antibodies. However, Env structure and organization in its native virion context has eluded detailed characterization. Here, we used cryo-electron tomog. to analyze Env in mature and immature HIV-1 particles. Immature particles showed distinct Env positioning relative to the underlying Gag lattice, providing insights into long-standing questions about Env incorporation. A 9.1-Å sub-tomogram-averaged reconstruction of virion-bound Env in conjunction with structural mass spectrometry revealed unexpected features, including a variable central core of the gp41 subunit, heterogeneous glycosylation between protomers, and a flexible stalk that allows Env tilting and variable exposure of neutralizing epitopes. Together, our results provide an integrative understanding of HIV assembly and structural variation in Env antigen presentation.

Cell (Cambridge, MA, United States) published new progress about Antibodies and Immunoglobulins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 2127-03-9 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2S2, Computed Properties of 2127-03-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zhou, Pengpeng; Chen, Chuan; Li, Shubai published the artcile< Selectfluor-initiated cyanation of disulfides to thiocyanates>, Electric Literature of 2127-03-9, the main research area is disulfide trimethylsilyl cyanide Selectfluor promoter cyanation green chem; thiocyanate preparation.

A Selectfluor-initiated cyanation of disulfides to thiocyanates was developed. In this process, Selectfluor was employed as the oxidant and trimethylsilyl cyanide was used as the cyanation reagent. It provides an eco-friendly and simple way to synthesize the thiocyanates.

Journal of Chemical Research published new progress about Cyanation. 2127-03-9 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2S2, Electric Literature of 2127-03-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Mathuri, Ashis; Pramanik, Milan; Parida, Amarchand; Mal, Prasenjit published the artcile< Disulfide metathesis via sulfur···iodine interaction and photoswitchability>, Synthetic Route of 2127-03-9, the main research area is unsym disulfide preparation; sym disulfide cross metathesis reaction photoswitchable.

Herein, the synthesis of unsym. diaryl disulfides RSSR1 (R = 2-MeC6H4, furan-2-ylmethyl, pyridin-2-yl, etc., R1 = CH2CHMe2, cyclohexyl, 4-ClC6H4, etc.) from two sym. disulfides RSSR and R1SSR1 via a cross-metathesis reaction which was controlled by a weak sulfur···iodine (S···I) interaction is reported. The unsym. disulfides were stable in acetonitrile solution in the presence of N-iodosuccinimide (NIS), and were found to be reversibly photoswitchable to the sym. disulfides under visible light irradiation

Organic & Biomolecular Chemistry published new progress about Aromatic compounds, disulfides Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 2127-03-9 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2S2, Synthetic Route of 2127-03-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Hu, Yechen; Li, Yang; Gao, Hang; Jiang, Bo; Zhang, Xiaodan; Li, Xiao; Wu, Qiong; Liang, Zhen; Zhang, Lihua; Zhang, Yukui published the artcile< Cleavable hydrophobic derivatization strategy for enrichment and identification of phosphorylated lysine peptides>, Synthetic Route of 2127-03-9, the main research area is lysine phosohopeptide derivatization; Cleavable hydrophobic derivatization; Liquid chromatography–tandem mass spectrometry; N-Phosphorylation; Phosphorylated lysine peptides; Proteomics.

Because of structural flexibility and acid lability, the identification of phosphorylated lysine (pLys) peptides is a great challenge. The authors report here a cleavable hydrophobic derivatization (CHD) strategy for the enrichment and identification of pLys peptides. First, 2,5-dioxopyrrolidin-1-yl-3-(decyldithio)propanoate was synthesized to react with dephosphorylated lysine peptides, and then the derived peptides were captured by a C18 column, followed by cleavage of the hydrophobic chain, with the specific label left on the target peptides for further identification. By CHD, the enrichment of pLys peptides from interfering peptides (1:1000 mass ratio) was achieved. Furthermore, CHD was applied to screen the pLys targets from Escherichia coli lysates, and 39 pLys sites from 35 proteins were identified. Gene Ontol. (GO) anal. showed that these proteins played vital roles in catabolism, metabolism, biogenesis, and biosynthetic processes. All these results demonstrate that CHD might pave the way for comprehensive profiling of the pLys proteome.

Analytical and Bioanalytical Chemistry published new progress about Escherichia coli. 2127-03-9 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2S2, Synthetic Route of 2127-03-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zhou, Man; Luo, Yan; Zeng, Weijia; Yang, Xiaoqing; Chen, Tingting; Zhang, Lulu; He, Xiaoyan; Yi, Xiuguang; Li, Yongxiu; Yi, Xiaoqing published the artcile< A co-delivery system based on a dimeric prodrug and star-shaped polymeric prodrug micelles for drug delivery>, Application of C10H8N2S2, the main research area is paclitaxel reduced glutathione dimeric polymeric prodrug delivery system; dimeric prodrug; drug delivery; high drug loading; polymeric prodrug micelles; reduction-sensitive.

Chemotherapy is one of the commonly used therapies for the treatment of malignant tumors. Insufficient drug-loading capacity is the major challenge for polymeric micelle-based drug delivery systems of chemotherapy. Here, the redox-responsive star-shaped polymeric prodrug (PSSP) and the dimeric prodrug of paclitaxel (PTX) were prepared Then the dimeric prodrug of PTX (diPTX, diP) was loaded into the core of the star-shaped polymeric prodrug micelles of PSSP by hydrophobic interaction forming the redox-responsive prodrug micelles of diPTX@PSSP for intracellular drug release in tumor cells. The hydrodynamic diameter of diPTX@PSSP nanoparticles was 114.3 nm ± 2.1 (PDI = 0.219 ± 0.016), and the micelles had long-term colloidal stability and the drugloading content (DLC) of diPTX and PTX is 16.7 and 46.9%, resp. The prepared micelles could broke under the reductive microenvironment within tumor cells, as a result, the dimeric prodrug of diP and polymeric prodrug micelles of PSSP were rapidly disassembled, leading to the rapid release of intracellular drugs. In vitro release studies showed that under the condition of reduced glutathione (GSH) (10 mM), the release of PTX was significantly accelerated with approx. 86.6% released within 21 h, and the released PTX in cytoplasm could promote the disintegration of microtubules and induce cell apoptosis. These results indicated that the new type of this reduction-sensitive nanodrug delivery system based on dimeric prodrug@polymeric prodrug micelles would be a promising technol. in chemotherapy.

Frontiers in Chemistry (Lausanne, Switzerland) published new progress about Cytotoxicity. 2127-03-9 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2S2, Application of C10H8N2S2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Close, Anne-Francoise; Chae, Heeyoung; Jonas, Jean-Christophe published the artcile< The lack of functional nicotinamide nucleotide transhydrogenase only moderately contributes to the impairment of glucose tolerance and glucose-stimulated insulin secretion in C57BL/6J vs C57BL/6N mice>, Safety of 1,2-Di(pyridin-2-yl)disulfane, the main research area is nicotinamide nucleotide transhydrogenase glucose tolerance insulin; Genetic background; Glucose homeostasis; Glutathione redox state; Insulin secretion; Mitochondria; NADPH.

Nicotinamide nucleotide transhydrogenase (NNT) is involved in mitochondrial NADPH production and its spontaneous inactivating mutation (NntTr [Tr, truncated]) is usually considered to be the main cause of the lower glucose tolerance of C57BL/6J vs C57BL/6N mice. However, the impact of this mutation on glucose tolerance remains disputed. Here, we singled out the impact of NntTr from that of other genetic variants between C57BL/6J and C57BL/6N mice on mitochondrial glutathione redox state (EGSH), glucose-stimulated insulin secretion (GSIS) and glucose tolerance. Male and female N5BL/6J mice that express wild-type Nnt (NntWT) or NntTr (N5-WT and N5-Tr mice) on the C57BL/6J genetic background were obtained by crossing N5BL/6J NntWT/Tr heterozygous mice. C57BL/6J and C57BL/6N mice were from Janvier Laboratories The Nnt genotype was confirmed by PCR and the genetic background by whole genome sequencing of one mouse of each type. Glucose tolerance was assessed by IPGTT, ITT and fasting/refeeding tests. Stimulus-secretion coupling events and GSIS were measured in isolated pancreatic islets. Cytosolic and mitochondrial EGSH were measured using the fluorescent redox probe GRX1-roGFP2 (glutaredoxin 1 fused to redox-sensitive enhanced GFP). The Nnt genotype and genetic background of each type of mouse were confirmed. As reported previously in C57BL/6N vs C57BL/6J islets, the glucose regulation of mitochondrial (but not cytosolic) EGSH and of NAD(P)H autofluorescence was markedly improved in N5-WT vs N5-Tr islets, confirming the role of NNT in mitochondrial redox regulation. However, ex vivo GSIS was only 1.2-1.4-times higher in N5-WT vs N5-Tr islets, while it was 2.4-times larger in C57BL/6N vs N5-WT islets, questioning the role of NNT in GSIS. In vivo, the ITT results did not differ between N5-WT and N5-Tr or C57BL/6N mice. However, the glucose excursion during an IPGTT was only 15-20% lower in female N5-WT mice than in N5-Tr and C57BL/6J mice and remained 3.5-times larger than in female C57BL/6N mice. Similar observations were made during a fasting/refeeding test. A slightly larger (∼30%) impact of NNT on glucose tolerance was found in males. Although our results confirm the importance of NNT in the regulation of mitochondrial redox state by glucose, they markedly downsize the role of NNT in the alteration of GSIS and glucose tolerance in C57BL/6J vs C57BL/6N mice. Therefore, documenting an NntWT genotype in C57BL/6 mice does not provide proof that their glucose tolerance is as good as in C57BL/6N mice.

Diabetologia published new progress about DNA Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 2127-03-9 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2S2, Safety of 1,2-Di(pyridin-2-yl)disulfane.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Khayat, Maan T.; Omar, Abdelsattar M.; Elfaky, Mahmoud A.; Muhammad, Yosra A.; Felemban, Elaf A.; El-Say, Khalid M.; El-Araby, Moustafa E. published the artcile< Reexamining povarov reaction′s scope and limitation in the generation of HCV-NS4A peptidomimetics>, Recommanded Product: tert-Butyl (5-aminopyridin-2-yl)carbamate, the main research area is hepatitis C virus NS4A peptidomimetics.

Chronic Hepatitis C is a global health threat and a silent killer. Regardless of the profound progress in preventing and treating this disease, research continues to discover new direct antiviral agents (DAAs), especially against novel targets. Our research has been directed to leverage the NS4A binding site to develop peptidomimetic inhibitors of the hepatitis C virus (HCV) NS3 protease. In previous reports, we could provide evidence of tunability of this site by peptide and nonpeptide NS3/4A inhibitors. In this report, we used structure-based techniques to design 1,2,3,4-tetrahydro-1,7-naphthyridine derivative as NS4A core mimics that cover the region between residues Ile-25′ to Arg-28′. The synthetic plan featured the Povarov reaction as an efficient strategy to construct the 1,7-naphthyridine core. Although this reaction has been reported in many literatures, critical assessments for its scope and limitations are scarce. In our work, we found that Povarov was extremely sensitive to alkene and aldehyde reactants. Moreover, using pyridine amines was not as successful as anilines. The most striking results were the lack of stability of compounds during purification and storage. The four compounds that survived the stability problems (1a-1d) did not show significant binding potency with NS3, because their structures were too simple to resemble the originally planned compounds

Heteroatom Chemistry published new progress about Aggregation (temperature). 220731-04-4 belongs to class pyridine-derivatives, and the molecular formula is C10H15N3O2, Recommanded Product: tert-Butyl (5-aminopyridin-2-yl)carbamate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem