Tag: M.W=200-250

Vitorino, Philip; Yeung, Stacey; Crow, Ailey; Bakke, Jesse; Smyczek, Tanya; West, Kristina; McNamara, Erin; Eastham-Anderson, Jeffrey; Gould, Stephen; Harris, Seth F.; Ndubaku, Chudi; Ye, Weilan published the artcile< MAP4K4 regulates integrin-FERM binding to control endothelial cell motility>, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is MAP4K4 moesin talin beta1 integrin vascular endothelial cell migration; angiogenesis inhibitor synthesis MAP4K4 signaling plasma membrane retraction HUVEC.

Cell migration is a stepwise process that coordinates multiple mol. machineries. Using in vitro angiogenesis screens with short interfering RNA and chem. inhibitors, we define here a MAP4K4-moesin-talin-β1-integrin mol. pathway that promotes efficient plasma membrane retraction during endothelial cell migration. Loss of MAP4K4 decreased membrane dynamics, slowed endothelial cell migration, and impaired angiogenesis in vitro and in vivo. In migrating endothelial cells, MAP4K4 phosphorylates moesin in retracting membranes at sites of focal adhesion disassembly. Epistasis analyses indicated that moesin functions downstream of MAP4K4 to inactivate integrin by competing with talin for binding to β1-integrin intracellular domain. Consequently, loss of moesin (encoded by the MSN gene) or MAP4K4 reduced adhesion disassembly rate in endothelial cells. Addnl., α5β1-integrin blockade reversed the membrane retraction defects associated with loss of Map4k4 in vitro and in vivo. Our study uncovers a novel aspect of endothelial cell migration. Finally, loss of MAP4K4 function suppressed pathol. angiogenesis in disease models, identifying MAP4K4 as a potential therapeutic target.

Nature (London, United Kingdom) published new progress about Angiogenesis. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

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

Gazzard, Lewis; Williams, Karen; Chen, Huifen; Axford, Lorraine; Blackwood, Elizabeth; Burton, Brenda; Chapman, Kerry; Crackett, Peter; Drobnick, Joy; Ellwood, Charles; Epler, Jennifer; Flagella, Michael; Gancia, Emanuela; Gill, Matthew; Goodacre, Simon; Halladay, Jason; Hewitt, Joanne; Hunt, Hazel; Kintz, Samuel; Lyssikatos, Joseph; Macleod, Calum; Major, Sarah; Medard, Guillaume; Narukulla, Raman; Ramiscal, Judi; Schmidt, Stephen; Seward, Eileen; Wiesmann, Christian; Wu, Ping; Yee, Sharon; Yen, Ivana; Malek, Shiva published the artcile< Mitigation of Acetylcholine Esterase Activity in the 1,7-Diazacarbazole Series of Inhibitors of Checkpoint Kinase 1>, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is diazacarbazole preparation checkpoint kinase 1 inhibitor structure activity antitumor.

Checkpoint kinase 1 (ChK1) plays a key role in the DNA damage response, facilitating cell-cycle arrest to provide sufficient time for lesion repair. This leads to the hypothesis that inhibition of ChK1 might enhance the effectiveness of DNA-damaging therapies in the treatment of cancer. Lead compound 1 (GNE-783), the prototype of the 1,7-diazacarbazole class of ChK1 inhibitors, was found to be a highly potent inhibitor of acetylcholine esterase (AChE) and unsuitable for development. A campaign of analog synthesis established SAR delineating ChK1 and AChE activities and allowing identification of new leads with improved profiles. In silico docking using a model of AChE permitted rationalization of the observed SAR. Compounds 19 (GNE-900) and 30 (GNE-145) were identified as selective, orally bioavailable ChK1 inhibitors offering excellent in vitro potency with significantly reduced AChE activity. In combination with gemcitabine, these compounds demonstrate an in vivo pharmacodynamic effect and are efficacious in a mouse p53 mutant xenograft model.

Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Safety of 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>, Formula: C11H17BN2O2, 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 Science published 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, Formula: C11H17BN2O2.

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

Raja Sekhara Reddy, B.; Pratap Reddy Gajulapalli, V.; Madhu Rekha, Estharla; Siva Krishna, Vagolu; Sriram, Dharmarajan; Sudakar Babu, K.; Kim, Eunha published the artcile< Design, synthesis, and in vitro biological evaluation of dehydroaripiprazole derivatives as antituberculosis agents and molecular docking study>, HPLC of Formula: 76535-74-5, the main research area is dehydroaripiprazole derivative antituberculosis agent biol mol docking.

In this study, we describe the synthesis of novel piperazine-substituted 7-(4-chlorobutoxy) quinolin-2(1H) derivatives 5a-z, which were designed through specific structural modifications of aripiprazole. Furthermore, the synthesized derivatives were described as potent in vitro inhibitors of Mycobacterium tuberculosis (MTB) H37Rv strain growth. Among these compounds, 5c, 5 h, and 5r were found to be the most active ones with a MIC of 0.78 μg/mL. This activity is better compared to that of ethambutol (MIC = 1.56 μg/mL). These compounds failed to inhibit normal RAW 264.7 macrophages. Moreover, in vitro findings were supported by mol. docking studies with the known anti-TB target (InhA). The mol. docking studies on 5c, 5 h, and 5r hit compounds clearly validated hydrogen bonds interactions with the Enoyl-acp reductase (INHA). Therefore, these results indicate that this class of compounds may provide candidates for future development, and hopefully provide drug alternatives for tuberculosis treatment.

Results in Chemistry published new progress about Cytotoxicity. 76535-74-5 belongs to class piperazines, and the molecular formula is C9H19ClN2O2, HPLC of Formula: 76535-74-5.

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

Cheng, Chuanjie; Sun, Jianwei; Xing, Lixin; Xu, Jimin; Wang, Xinyan; Hu, Yuefei published the artcile< Highly Chemoselective Pd-C Catalytic Hydrodechlorination Leading to the Highly Efficient N-Debenzylation of Benzylamines>, SDS of cas: 76535-74-5, the main research area is benzylamine debenzylation synergistic trichloroethane chemoselective hydrodechlorination palladium catalyst; amine hydrochloride preparation.

In the presence of 1,1,2-trichloroethane, a novel procedure for the Pd-C catalytic N-debenzylation of benzylamines was established. The method proceeded in a synergistic catalytic system and directly gave the products as crystalline amine hydrochlorides in practically quant. yields.

Journal of Organic Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent) (benzylic). 76535-74-5 belongs to class piperazines, and the molecular formula is C9H19ClN2O2, SDS of cas: 76535-74-5.

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

Du, Lifei; Wang, Xiaoyu; Cui, Guonan; Xu, Bailing published the artcile< Design, synthesis and biological evaluation of novel thiazole-based derivatives as human Pin1 inhibitors>, Recommanded Product: tert-Butyl piperazine-1-carboxylate hydrochloride, the main research area is thiazole based derivative human Pin1 inhibitors; PPIase; Pin1; Pin1 inhibitor; Thiazole derivatives.

Pin1 is a peptidyl prolyl cis-trans isomerase (PPIase) and inhibiting Pin1 is a potential way for discovering anti-tumor agents. With an aim to find potent Pin1 inhibitors with a novel scaffold, a series of thiazole derivatives with an alicyclic heterocycles on the 2-position were designed, synthesized and tested against human Pin1. Compound 9p bearing a 2-oxa-6-azaspiro [3,3] heptane moiety on the thiazole scaffold was identified as the most potent Pin1 inhibitor of this series with an IC50 value of 0.95μM. The structure-activity relationship (SAR) and mol. modeling study indicated that introducing an alicyclic ring with an H-bond acceptor would be a viable way to improve the binding affinity.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 76535-74-5 belongs to class piperazines, and the molecular formula is C9H19ClN2O2, Recommanded Product: tert-Butyl piperazine-1-carboxylate hydrochloride.

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

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