Month: October 2022

Song, Fengbin; Xu, Guozhang; Gaul, Michael D.; Zhao, Baoping; Lu, Tianbao; Zhang, Rui; DesJarlais, Renee L.; DiLoreto, Karen; Huebert, Norman; Shook, Brian; Rentzeperis, Dennis; Santulli, Rosie; Eckardt, Annette; Demarest, Keith published the artcile< Design, synthesis and structure activity relationships of indazole and indole derivatives as potent glucagon receptor antagonists>, Name: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is design synthesis SAR indazole indole derivative glucagon receptor antagonist; Diabetes mellitus; Glucagon; Glucagon receptor antagonist; Indazole; Indole.

A novel series of indazole/indole derivatives were discovered as glucagon receptor (GCGR) antagonists through scaffold hopping based on two literature leads: MK-0893 and LY-2409021. Further structure-activity relationship (SAR) exploration and optimization led to the discovery of multiple potent GCGR antagonists with excellent pharmacokinetic properties in mice and rats, including low systemic clearance, long elimination half-life, and good oral bioavailability. These potent GCGR antagonists could be used for potential treatment of type II diabetes.

Bioorganic & Medicinal Chemistry Letters published new progress about Conformation (conformational overlay with LY-2409021). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Name: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Gazzard, Lewis; Appleton, Brent; Chapman, Kerry; Chen, Huifen; Clark, Kevin; Drobnick, Joy; Goodacre, Simon; Halladay, Jason; Lyssikatos, Joseph; Schmidt, Stephen; Sideris, Steve; Wiesmann, Christian; Williams, Karen; Wu, Ping; Yen, Ivana; Malek, Shiva published the artcile< Discovery of the 1,7-diazacarbazole class of inhibitors of checkpoint kinase 1>, Formula: C11H17BN2O2, the main research area is crystal structure diazacarbazole preparation checkpoint kinase inhibitor; ChK1; Checkpoint; Diazacarbazole; GNE-783; Structure-based design.

Checkpoint kinase 1 (ChK1) is activated in response to DNA damage, acting to temporarily block cell cycle progression and allow for DNA repair. It is envisaged that inhibition of ChK1 will sensitize tumor cells to treatment with DNA-damaging therapies, and may enhance the therapeutic window. High throughput screening identified carboxylate-containing diarylpyrazines as a prominent hit series, but with limited biochem. potency and no cellular activity. Through a series of SAR investigations and x-ray crystallog. anal. the critical role of polar contacts with conserved waters in the kinase back pocket was established. Structure-based design, guided by in silico modeling, transformed the series to better satisfy these contacts and the novel 1,7-diazacarbazole class of inhibitors was discovered. Here the authors present the genesis of this novel series and the identification of GNE-783 I, a potent, selective and orally bioavailable inhibitor of ChK1.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Formula: C11H17BN2O2.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Yin, Huanhuan; Dong, Jingjing; Cai, Yingchun; Shi, Ximeng; Wang, Hao; Liu, Guixia; Tang, Yun; Liu, Jianwen; Ma, Lei published the artcile< Design, synthesis and biological evaluation of chalcones as reversers of P-glycoprotein-mediated multidrug resistance>, Application of C16H22N2O3, the main research area is chalcone design synthesis anticancer reversers glycoprotein multidrug resistance; Chalcones; Inhibitors docking; Multidrug resistance reversers; P-glycoprotein inhibitors; Structure-activity relationship.

Overexpression of P-glycoprotein (P-gp) is one of the major causes for multidrug resistance (MDR), which has become a major obstacle in cancer therapy. One hopeful approach to reverse the MDR is to develop inhibitors of P-gp in expression and/or function. Here, we designed and synthesized a series of chalcone derivatives as P-gp inhibitors and evaluated their potential reversal activities against MDR. Among them, the most active compound I had little intrinsic cytotoxicity and showed the highest activity (RF = 50.19) in reversing DOX resistance in MCF-7/DOX cells. Further studies demonstrated that I could increase intracellular accumulation of DOX and inhibit expression of P-gp at mRNA and protein levels. More importantly, I significantly enhanced the efficacy of DOX against the tumor xenografts bearing MCF-7/DOX cells with the precondition of unchanged body weight Therefore, I might represent a promising lead to develop MDR reversal agents for cancer chemotherapy.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Application of C16H22N2O3.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Papagni, Antonio; Del Buttero, Paola; Bertarelli, Chiara; Miozzo, Luciano; Moret, Massimo; Pryce, Mary T.; Rizzato, Silvia published the artcile< Novel fluorinated amino-stilbenes and their solid-state photodimerization>, Formula: C16H22N2O3, the main research area is fluorinated aminostilbene solid state photodimerization.

We synthesized a series of polyfluoroaminostilbenes in satisfactory yields by Wittig reaction of 4-piperazinylbenzalhehydes with pentafluorobenzylidenetriphenylphosphorane and we analyzed the photochem. behavior of these stilbenes in the solid state; thanks to arene-perfluoroarene π-π interactions, some of them have shown a good propensity to give the corresponding cyclobutane photodimers in quant. yields. The photocyclization is reversible both in solution and in polymeric matrix, affording the corresponding stilbenes with different cis-trans stereoselectivity.

New Journal of Chemistry published new progress about [2+2] Photocycloaddition reaction. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Formula: C16H22N2O3.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Antonow, Dyeison; Cooper, Nectaroula; Howard, Philip W.; Thurston, David E. published the artcile< Parallel Synthesis of a Novel C2-Aryl Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) Library>, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is pyrrolobenzodiazepine aryl parallel synthesis Suzuki coupling microwave irradiation.

A 66-membered library of C2-aryl pyrrolo[2,1-c][1,4]benzodiazepines I [R = Ph, 4-MeOC6H4, 3-H2NC6H4, 2-F3CC6H4, 4-(4-methyl-1-piperazinyl)phenyl, 2-thienyl, 4-pyridyl, 2-naphthyl, etc.] has been successfully prepared by parallel synthesis via Suzuki coupling using polystyrene-bound Pd(PPh3)4 as catalyst and polystyrene-bound diethanolamine as scavenger under microwave irradiation Library members were obtained in sufficient yields (up to 91%) and purity (85-98% crude) for biol. evaluation.

Journal of Combinatorial Chemistry published new progress about Boronic acids Role: RCT (Reactant), RACT (Reactant or Reagent). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Tintori, Cristina; Brai, Annalaura; Dasso Lang, Maria Chiara; Deodato, Davide; Greco, Antonia Michela; Bizzarri, Bruno Mattia; Cascone, Lorena; Casian, Alexandru; Zamperini, Claudio; Dreassi, Elena; Crespan, Emmanuele; Maga, Giovanni; Vanham, Guido; Ceresola, Elisa; Canducci, Filippo; Arien, Kevin K.; Botta, Maurizio published the artcile< Development and in Vitro Evaluation of a Microbicide Gel Formulation for a Novel Non-Nucleoside Reverse Transcriptase Inhibitor Belonging to the N-Dihydroalkyloxybenzyloxopyrimidines (N-DABOs) Family>, COA of Formula: C16H22N2O3, the main research area is HIV1 antiviral gel dihydroalkyloxybenzyl oxopyrimidine.

Preventing HIV transmission by the use of a vaginal microbicide is a topic of considerable interest in the fight against AIDS. Both a potent anti-HIV agent and an efficient formulation are required to develop a successful microbicide. In this regard, mols. able to inhibit the HIV replication before the integration of the viral DNA into the genetic material of the host cells, such as entry inhibitors or reverse transcriptase inhibitors (RTIs), are ideal candidates for prevention purpose. Among RTIs, S- and N-dihydroalkyloxybenzyloxopyrimidines (S-DABOs and N-DABOs) are interesting compounds active at nanomolar concentration against wild type of RT and with a very interesting activity against RT mutations. Herein, novel N-DABOs were synthesized and tested as anti-HIV agents. Furthermore, their mode of binding was studied by mol. modeling. At the same time, a vaginal microbicide gel formulation was developed and tested for one of the most promising candidates.

Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, COA of Formula: C16H22N2O3.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Verma, Sanjeev K.; Ghorpade, Ramarao; Pratap, Ajay; Kaushik, M. P. published the artcile< CDI-mediated monoacylation of symmetrical diamines and selective acylation of primary amines of unsymmetrical diamines>, COA of Formula: C9H19ClN2O2, the main research area is CDI monoacylation sym diamine acylation amine unsym.

A highly efficient and green protocol for monoacylation of sym. diamines and chemoselective acylation of primary amines of unsym. diamines was developed.

Green Chemistry published new progress about Acylation. 76535-74-5 belongs to class piperazines, and the molecular formula is C9H19ClN2O2, COA of Formula: C9H19ClN2O2.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Myers, Samuel H.; Temps, Carolin; Houston, Douglas R.; Brunton, Valerie G.; Unciti-Broceta, Asier published the artcile< Development of Potent Inhibitors of Receptor Tyrosine Kinases by Ligand-Based Drug Design and Target-Biased Phenotypic Screening>, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is pyrazolo pyrimidine derivative preparation enzyme inhibitor cancer.

Pyrazolopyrimidines with potent antiproliferative properties were developed by an adaptive strategy that applies ligand-based design and phenotypic screening iteratively and is informed by biochem. assays. To drive development toward specific oncopathways, compounds were tested against cancer cells that overexpress, or not, AXL kinase. Identified phenotypic hits were found to inhibit oncotargets AXL, RET, and FLT3. Subsequent optimization generated antiproliferative lead compounds with unique selectivity profiles, including selective AXL inhibitors and a highly potent inhibitor of FLT3.

Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Jouffroy, Matthieu; Kelly, Christopher B.; Molander, Gary A. published the artcile< Thioetherification via Photoredox/Nickel Dual Catalysis>, Electric Literature of 374930-88-8, the main research area is thioether aryl heteroaryl preparation; aryl heteroaryl bromide thioetherification thiol hypervalent alkylsilicate nickel photoredox.

Hypervalent alkylsilicates represent new and readily accessible precursors for the generation of alkyl radicals under photoredox conditions. Alkyl radicals generated from such silicates serve as effective hydrogen atom abstractors from thiols, furnishing thiyl radicals. The reactive sulfur species generated in this manner can be funneled into a nickel-mediated cross-coupling cycle employing aromatic bromides to furnish thioethers. The serendipitous discovery of this reaction and its utilization for the thioetherification of various aryl and heteroaryl bromides with a diverse array of thiols are described. The S-H selective H atom abstraction event enables a wide range of functional groups, including those bearing protic moieties, to be tolerated.

Organic Letterspublished new progress about Aryl bromides Role: RCT (Reactant), RACT (Reactant or Reagent). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Electric Literature of 374930-88-8.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Lee, Heajin; Liu, Wenjun; Brown, Adrienne S.; Landgraf, Ralf; Wilson, James N. published the artcile< Fluorescent Kinase Probes Enabling Identification and Dynamic Imaging of HER2(+) Cells>, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is fluorescent kinase probe imaging HER2 cancer.

The human epidermal growth factor receptor, EGFR/ERBB/HER, family of receptor tyrosine kinases is central to many signaling pathways and a validated chemotherapy target in multiple cancers. While EGFR/ERBB-targeted therapies, including monoclonal antibodies, e.g., trastuzumab, and small mol. kinase inhibitors, such as lapatinib, have been developed, rapid identification and classification of cancer cells is key to identifying the best treatment regime. The authors report ERBB2 (also HER2) targeting kinase probes that exhibit a “”turn-on”” emission response upon binding. These live cell compatible probes differentiate ERBB2(+) cells from low-level, ERBB2(-) cells by targeting the intracellular ATP-binding pocket of ERBB2 with therapeutic inhibitor-like specificity. Beyond kinase expression levels, probe signal is linked to the phosphotyrosine-correlated activation state of the ERBB2 population. Addnl., the rapid signaling capability of the probes can report changes in activation state in live cells providing a unique type of complementary information to immunohistochem. assays of receptor kinase populations.

Analytical Chemistry (Washington, DC, United States)published new progress about Confocal laser scanning microscopy. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics