Category: piperazines

Sanchez-Arias, Juan A.; Rabal, Obdulia; Cuadrado-Tejedor, Mar; de Miguel, Irene; Perez-Gonzalez, Marta; Ugarte, Ana; Saez, Elena; Espelosin, Maria; Ursua, Susana; Haizhong, Tan; Wei, Wu; Musheng, Xu; Garcia-Osta, Ana; Oyarzabal, Julen published the artcile< Impact of Scaffold Exploration on Novel Dual-Acting Histone Deacetylases and Phosphodiesterase 5 Inhibitors for the Treatment of Alzheimer's Disease>, Formula: C13H19BrN4O2, the main research area is histone deacetylase phosphodiesterase 5 inhibitor preparation Alzheimer treatment; Alzheimer’s disease; HDACs; PDE5; dual inhibitor; tadalafil; vardenafil.

A novel systems therapeutics approach, involving simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylase (HDAC), has been validated as a potentially novel therapeutic strategy for the treatment of Alzheimer’s disease (AD). First-in-class dual inhibitors bearing a sildenafil core have been very recently reported, and the lead mol. CM-414 has proven this strategy in AD animal models. Because scaffolds may play a critical role in primary activities and ADME-Tox profiling as well as on intellectual property, the authors have explored alternative scaffolds (vardenafil- and tadalafil-based cores) and evaluated their impact on critical parameters such as primary activities, permeability, toxicity, and in vivo (pharmacokinetics and functional response in hippocampus) to identify a potential alternative lead mol. bearing a different chemotype for in vivo testing.

ACS Chemical Neuroscience published new progress about Alzheimer disease. 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Formula: C13H19BrN4O2.

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

Link, Achim; Zhou, Yujing; Buchwald, Stephen L. published the artcile< CuH-Catalyzed Asymmetric Reductive Amidation of α,β-Unsaturated Carboxylic Acids>, Computed Properties of 374930-88-8, the main research area is chiral amide preparation enantioselective amidation carboxylic acid secondary amine.

The direct enantioselective copper hydride (CuH)-catalyzed synthesis of β-chiral amides from α,β-unsaturated carboxylic acids and secondary amines under mild reaction conditions is reported. The method utilizes readily accessible carboxylic acids and tolerates a variety of functional groups in the β-position including several heteroarenes. A subsequent iridium-catalyzed reduction to γ-chiral amines can be performed in the same flask without purification of the intermediate amides.

Organic Letters published new progress about Amidation (Reductive). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Computed Properties of 374930-88-8.

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

Shallal, Hassan M.; Russu, Wade A. published the artcile< Discovery, synthesis, and investigation of the antitumor activity of novel piperazinylpyrimidine derivatives>, SDS of cas: 374930-88-8, the main research area is piperazinylpyrimidine derivative preparation antitumor activity breast carcinoma kinase profiling.

Protein kinases play several pertinent roles in cell proliferation, and targeting these proteins has been shown to be a successful strategy toward controlling different malignancies. Despite the great discovery stories during the last two decades, there is still a demand for anticancer small mols. with the potential of being selective on both the protein kinase and/or the cellular level. A series of novel piperazinylpyrimidine compounds was synthesized and the members tested for their potential to selectively inhibit the growth of certain tumor cell lines included within the NCI-60 cell line panel. MDA-MB-468, a triple-neg./basal-like breast carcinoma cell line was among the most sensitive cell lines towards compounds I and II. The three most interesting compounds identified in cellular screens (I, II, and III) were subjected to kinase profiling and found to have an interesting selective tendency to target certain kinase subfamily members; PDGFR, CK1, RAF and others. Compound I showed a selective tendency to bind to and/or inhibit the function of certain KIT and PDGFRA mutants compared to their wild-type isoforms. Piperazinylpyrimidine based derivatives represent a new class of selective kinase inhibitors. Significantly, I is more potent at inhibiting oncogenic mutant forms of PDGFR family kinases, which is relevant in terms of its potential use in treating tumors that have become resistant to treatment or driven by such mutations. The clin. demand for agents useful in the control of triple-neg./basal-like breast cancer justifies interest in compound II which is a potent growth inhibitor of MDA-MB-468 cell line.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, SDS of cas: 374930-88-8.

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

Zhang, Wei; Benmohamed, Radhia; Arvanites, Anthony C.; Morimoto, Richard I.; Ferrante, Robert J.; Kirsch, Donald R.; Silverman, Richard B. published the artcile< Cyclohexane 1,3-diones and their inhibition of mutant SOD1-dependent protein aggregation and toxicity in PC12 cells>, Reference of 197638-83-8, the main research area is cyclohexanedione preparation inhibition mutant SOD1 dependent protein aggregation.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Currently, there is only one FDA-approved treatment for ALS (riluzole), and that drug only extends life, on average, by 2-3 mo. Mutations in Cu/Zn superoxide dismutase (SOD1) are found in familial forms of the disease and have played an important role in the study of ALS pathophysiol. On the basis of their activity in a PC12-G93A-YFP high-throughput screening assay, several bioactive compounds have been identified and classified as cyclohexane-1,3-dione (CHD) derivatives A concise and efficient synthetic route has been developed to provide diverse CHD analogs. The structural modification of the CHD scaffold led to the discovery of a more potent analog (I) with an EC50 of 700 nM having good pharmacokinetic properties, such as high solubility, low human and mouse metabolic potential, and relatively good plasma stability. It was also found to efficiently penetrate the blood-brain barrier. However, compound I did not exhibit any significant life span extension in the ALS mouse model. It was found that, although I was active in PC12 cells, it had poor activity in other cell types, including primary cortical neurons, indicating that it can penetrate into the brain, but is not active in neuronal cells, potentially due to poor selective cell penetration. Further structural modification of the CHD scaffold was aimed at improving global cell activity as well as maintaining potency. Two new analogs (II and III) were synthesized, which had significantly enhanced cortical neuronal cell permeability, as well as similar potency to that of I in the PC12-G93A assay. These CHD analogs are being investigated further as novel therapeutic candidates for ALS.

Bioorganic & Medicinal Chemistry published new progress about Aggregation (protein). 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Reference of 197638-83-8.

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

El Khatib, Mirna; Serafim, Ricardo Augusto Massarico; Molander, Gary A. published the artcile< α-Arylation/Heteroarylation of Chiral α-Aminomethyltrifluoro-borates by Synergistic Iridium Photoredox/Nickel Cross-Coupling Catalysis>, SDS of cas: 374930-88-8, the main research area is arylation heteroarylation aminomethyltrifluoroborate iridium photoredox nickel cross coupling catalyst; amino acids; cross-coupling; heterocycles; nickel; photochemistry.

Direct access to complex, enantiopure benzylamine architectures using a synergistic iridium photoredox/nickel cross-coupling dual catalysis strategy has been developed. New C(sp3)-C(sp2) bonds are forged starting from abundant and inexpensive natural amino acids.

Angewandte Chemie, International Edition published new progress about Amino acid esters Role: RCT (Reactant), RACT (Reactant or Reagent). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, SDS of cas: 374930-88-8.

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

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

Mondal, Milon; Unver, M. Yagiz; Pal, Asish; Bakker, Matthijs; Berrier, Stephan P.; Hirsch, Anna K. H. published the artcile< Fragment-Based Drug Design Facilitated by Protein-Templated Click Chemistry: Fragment Linking and -Optimization of Inhibitors of the Aspartic Protease Endothiapepsin>, Application of C16H22N2O3, the main research area is triazole protein templated click chem aspartic protease endothiapepsin inhibitor; click chemistry; drug design; enzymes; inhibitors; liquid chromatography.

There is an urgent need for the development of efficient methodologies that accelerate drug discovery. The authors demonstrate that the strategic combination of fragment linking/optimization and protein-templated click chem. is an efficient and powerful method that accelerates the hit-identification process for the aspartic protease endothiapepsin. The best binder, which inhibits endothiapepsin with an IC50 value of 43 μM, represents the first example of triazole-based inhibitors of endothiapepsin. The authors’ strategy could find application on a whole range of drug targets.

Chemistry – A European Journal published new progress about 1,3-Dipolar cycloaddition reaction. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Application of C16H22N2O3.

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

Miyamoto, Teruyuki; Matsumoto, Junichi; Chiba, Katsumi; Egawa, Hiroshi; Shibamori, Kohichiro; Minamida, Akira; Nishimura, Yoshiro; Okada, Hidetsugu; Kataoka, Masahiro published the artcile< Pyridonecarboxylic acids as antibacterial agents. Part 14. Synthesis and structure-activity relationships of 5-substituted 6,8-difluoroquinolones, including sparfloxacin, a new quinolone antibacterial agent with improved potency>, Reference of 22476-74-0, the main research area is cyclopropylfluoropiperazinylquinolonecarboxylate preparation bactericide; structure activity cyclopropylfluoropiperazinylquinolonecarboxylate bactericide; sparfloxacin preparation crystal structure bactericide; quinolonecarboxylic acid substituted preparation bactericide; piperazinylcyclopropylfluoroquinolonecarboxylic acid preparation bactericide.

A series of 5,7-disubstituted 1-cyclopropyl-6,8-difluoro-4-oxoquinoline-3-carboxylic acids, e.g., I (R = Cl, F, OH, NH2, SH, SMe, OMe, OCH2Ph, R1 = F, substituted piperazinyl) were prepared In vitro antibacterial screening results indicated that the amino group was optimal among the C-5 substituents. A combination of the C-5 amino group and the C-7 3,5-dimethylpiperazinyl appendage in this series conferred the best overall antibacterial property with no adverse drug interactions. I (R = NH2, R1 = cis-3,5-dimethylpiperazin-1-yl), was superior to ciprofloxacin in both in vitro and in vivo potency and hence was selected as a promising candidate for an improved therapeutic agent.

Journal of Medicinal Chemistry published new progress about Crystal structure. 22476-74-0 belongs to class piperazines, and the molecular formula is C6H12N2O, Reference of 22476-74-0.

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