Category: 229009-40-9

Li, Jing; Tan, Guishan; Cai, Yabo; Liu, Ruihuan; Xiong, Xiaolin; Gu, Baohua; He, Wei; Liu, Bing; Ren, Qingyun; Wu, Jianping; Chi, Bo; Zhang, Hang; Zhao, Yanzhong; Xu, Yangrui; Zou, Zhenxing; Kang, Fenghua; Xu, Kangping published the artcile< A novel Apigenin derivative suppresses renal cell carcinoma via directly inhibiting wild-type and mutant MET>, Reference of 229009-40-9, the main research area is human renal cell carcinoma apigenin derivative MET; Apigenin derivatives; Drug-resistant MET mutations; MET; MET downstream signaling; Renal cell carcinoma.

MET, the receptor of hepatocyte growth factor (HGF), is a driving factor in renal cell carcinoma (RCC) and also a proven drug target for cancer treatment. To improve the activity and to investigate the mechanisms of action of Apigenin (APG), novel derivatives of APG with improved properties were synthesized and their activities against Caki-1 human renal cancer cell line were evaluated. It was found that compound 15e exhibited excellent potency against the growth of multiple RCC cell lines including Caki-1, Caki-2 and ACHN and is superior to APG and Crizotinib. Subsequent investigations demonstrated that compound 15e can inhibit Caki-1 cell proliferation, migration and invasion. Mechanistically, 15e directly targeted the MET kinase domain, decreased its auto-phosphorylation at Y1234/Y1235 and inhibited its kinase activity and downstream signaling. Importantly, 15e had inhibitory activity against mutant MET V1238I and Y1248H which were resistant to approved MET inhibitors Cabozantinib, Crizotinib or Capmatinib. In vivo tumor graft study confirmed that 15e repressed RCC growth through inhibition of MET activation. These results indicate that compound 15e has the potential to be developed as a treatment for RCC, and especially against drug-resistant MET mutations.

Biochemical Pharmacology (Amsterdam, Netherlands) published new progress about Apoptosis. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Reference of 229009-40-9.

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

Yang, Wei; Liu, Xiaolong; Song, Chunli; Ji, Sen; Yang, Jianhong; Liu, Yang; You, Jing; Zhang, Jie; Huang, Shenzhen; Cheng, Wei; Shao, Zhenhua; Li, Linli; Yang, Shengyong published the artcile< Structure-activity relationship studies of phenothiazine derivatives as a new class of ferroptosis inhibitors together with the therapeutic effect in an ischemic stroke model>, SDS of cas: 229009-40-9, the main research area is SAR preparation phenothiazine derivative ferroptosis ischemic stroke BBB; Ferroptosis inhibitor; Ischemic stroke; Promethazine derivatives; Structure-activity relationship.

Ferroptosis is a new type of programmed cell death discovered recently and has been demonstrated to be involved in a number of human diseases such as ischemic stroke. Ferroptosis inhibitors are expected to have potential to treat these diseases. Herein, we report the identification of promethazine derivatives as a new type of ferroptosis inhibitors. Structure-activity relationship (SAR) analyses led to the discovery of the most potent compound 2-(1-(4-(4-methylpiperazin-1-yl)phenyl)ethyl)-10H-phenothiazine (51), which showed an EC50 (half maximal effective concentration) value of 0.0005μM in the erastin-induced HT1080 cell ferroptosis model. In the MCAO (middle cerebral artery occlusion) ischemic stroke model, 51 presented an excellent therapeutic effect. This compound also displayed favorable pharmacokinetic properties, in particular, a good ability to permeate the blood-brain barrier. Overall, 51 could be a promising lead compound for the treatment of ferroptosis related diseases and deserves further investigations.

European Journal of Medicinal Chemistry published new progress about Blood-brain barrier (permeation). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, SDS of cas: 229009-40-9.

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

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

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

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

Lee, Heajin; Landgraf, Ralf; Wilson, James N. published the artcile< Synthesis and photophysical properties of a fluorescent cyanoquinoline probe for profiling ERBB2 kinase inhibitor response>, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is cyanoquinoline fluorescent probe preparation ERBB2 kinase inhibitor; EGFR; ERBB; Fluorescent probe; Kinase inhibitor; Receptor tyrosine kinase.

A fluorescent probe targeting the ERBB2 receptor tyrosine was designed, synthesized and evaluated as reporter of ERBB2 dynamics in overexpressing BT474, i.e. Her2(+), cells. Two cyanoquinoline (CQ) probes modeled after type-I (CQ1, I) or active state and type-II (CQ2, II) or inactive state inhibitors were designed and synthesized with extended π systems that impart binding-induced, turn-on fluorescence. Solution spectroscopy revealed that I exhibited attractive photophys. properties and displayed turn-on emission in the presence of purified, soluble ERBB2 kinase domain, while II was found to be non-emissive, likely due to quenching via a photoinduced electron transfer mechanism. Live cell imaging with I revealed that this probe targeted an intracellular population of ERBB2, which increased following treatment with type-I inhibitors, gefinitib and canertinib, but showed no response to type-II inhibitors. I thus provides a novel means of imaging the dynamic response of ERBB2(+) cells to kinase inhibitors.

Bioorganic & Medicinal Chemistrypublished new progress about Density functional theory. 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

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

Lu, Xi; Wang, Xiao-Xu; Gong, Tian-Jun; Pi, Jing-Jing; He, Shi-Jiang; Fu, Yao published the artcile< Nickel-catalyzed allylic defluorinative alkylation of trifluoromethyl alkenes with reductive decarboxylation of redox-active esters>, Name: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is functionalized geminal difluoroalkene preparation; haloalkene redox active ester defluorinative reductive coupling nickel catalyst.

An efficient method was developed for the synthesis of functionalized gem-difluoroalkenes I [R = c-hexyl, 4-BrC6H4(CH2)2, 4-CNC6H4O(CH2)2C(Me)2, etc.; Ar = 3,4-(OMe)2C6H3, 4-PhC6H4, 2-naphthyl, etc.] via nickel-catalyzed defluorinative reductive cross-coupling of trifluoromethyl alkenes with redox-active esters. The present reaction involved C(sp3)-F bond cleavage and C(sp3)-C(sp3) bond formation under very mild reaction conditions, while tolerating many sensitive functional groups and requiring minimal substrate protection. Therefore, this method provided an efficient and convenient approach for late-stage modification of biol. interesting mols.

Chemical Sciencepublished new progress about Carboxylic esters Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 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