Category: 229009-40-9

Jain, Rama; Mathur, Michelle; Lan, Jiong; Costales, Abran; Atallah, Gordana; Ramurthy, Savithri; Subramanian, Sharadha; Setti, Lina; Feucht, Paul; Warne, Bob; Doyle, Laura; Basham, Stephen; Jefferson, Anne B.; Lindvall, Mika; Appleton, Brent A.; Shafer, Cynthia M. published the artcile< Discovery of Potent and Selective RSK Inhibitors as Biological Probes>, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is difluorophenol pyridine RSK inhibitor preparation antitumor.

While the p90 ribosomal S6 kinase (RSK) family has been implicated in multiple tumor cell functions, the full understanding of this kinase family has been restricted by the lack of highly selective inhibitors. A bis-phenol pyrazole was identified from high-throughput screening as an inhibitor of the N-terminal kinase of RSK2. Structure-based drug design using crystallog., conformational anal., and scaffold morphing resulted in highly optimized difluorophenol pyridine inhibitors of the RSK kinase family as demonstrated cellularly by the inhibition of YB1 phosphorylation. These compounds provide for the first time in vitro tools with an improved selectivity and potency profile to examine the importance of RSK signaling in cancer cells and to fully evaluate RSK as a therapeutic target.

Journal of Medicinal Chemistry published new progress about Antitumor 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

Jiang, Cheng-Shi; Fu, Yan; Zhang, Li; Gong, Jing-Xu; Wang, Zhen-Zhong; Xiao, Wei; Zhang, Hai-Yan; Guo, Yue-Wei published the artcile< Synthesis and biological evaluation of novel marine-derived indole-based 1,2,4-oxadiazoles derivatives as multifunctional neuroprotective agents>, SDS of cas: 229009-40-9, the main research area is indole oxadiazole preparation SAR neurotoxicity neuroprotective activity Alzheimer; 1,2,4-Oxadiazole derivatives; Amyloid-β-peptide; Neuroprotective activity; Oxygen–glucose deprivation; Phidianidines.

Phidianidines I [R = H, Br], isolated from the marine opisthobranch mollusk Phidiana militaris, present the first example of natural products possessing an 1,2,4-oxadiazole ring system and show various bioactivities. However, the structure-activity relationship study related to I has not been reported yet. As our ongoing effect toward marine-derived potential neuroprotective agents, a series of phidianidine-based derivatives II [R = ph, 4-Me-C6H4, 4-Et-C6H4, etc.] have been synthesized and evaluated for neuroprotective effects against amyloid-β25-35 (Aβ25-35)-, hydrogenperoxide (H2O2)-, and oxygen-glucose deprivation (OGD)-induced neurotoxicity in SH-SY5Y cells. The bioassay results indicated that some of analogs, especially II [R = 4-OEt-C6H4] and II [R = 4-OPr-C6H4], exhibited good in vitro neuroprotective effects in the above three screening models. The preliminary SAR study indicated that substituent groups introduced to the benzene ring play a crucial role in their bioactivity. In particular, the linear alkoxy group at 4-position favors the neuroprotective activity, while a bulky group could lead the activity decrease or loss. These findings could provide an alternative strategy for the development of novel indole-based 1,2,4-oxadiazole derivatives for the treatment of Alzheimer’s disease.

Bioorganic & Medicinal Chemistry Letters published new progress about Alzheimer disease. 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

Velagapudi, Sai Pradeep; Luo, Yiling; Tran, Tuan; Haniff, Hafeez S.; Nakai, Yoshio; Fallahi, Mohammad; Martinez, Gustavo J.; Childs-Disney, Jessica L.; Disney, Matthew D. published the artcile< Defining RNA-Small Molecule Affinity Landscapes Enables Design of a Small Molecule Inhibitor of an Oncogenic Noncoding RNA>, Related Products of 229009-40-9, the main research area is RNA binding small mol inhibitor preparation antitumor screening.

RNA drug targets are pervasive in cells but methods to design small mols. that target them are sparse. Herein, the authors report a general approach to score the affinity and selectivity of RNA motif-small mol. interactions identified via selection. Named High Throughput Structure-Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif-small mol. binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small mol. and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small mol., Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, derepressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chem. Cross Linking and Isolation by Pull Down (Chem-CLIP), a covalent small mol.-RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small mol. drugging of noncoding RNAs.

ACS Central Science published new progress about Antitumor agents. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Related Products of 229009-40-9.

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>, SDS of cas: 229009-40-9, 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, SDS of cas: 229009-40-9.

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>, Synthetic Route of 229009-40-9, 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, Synthetic Route of 229009-40-9.

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>, SDS of cas: 229009-40-9, 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, 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>, Category: piperazines, 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, Category: piperazines.

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>, Quality Control of 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, Quality Control of 229009-40-9.

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

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>, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, 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, 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>, COA of Formula: C11H17BN2O2, 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 Chemistry published new progress about Density functional theory. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, COA of Formula: C11H17BN2O2.

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