Month: November 2022

Zhang, Lei published the artcileA multiplexed cell assay in HepG2 cells for the identification of Δ5, Δ6, and Δ9 desaturase and elongase inhibitors, Related Products of piperazines, the publication is Journal of Biomolecular Screening (2010), 15(2), 169-176, database is CAplus and MEDLINE.

A multiplexed cell assay has been optimized to measure the activities of fatty acyl-CoA elongase, Δ5 desaturase (Δ5D), Δ6 desaturase (Δ6D), and Δ9 desaturase (Δ9D) together using ¹⁴C-labeled tracers in HepG2 cells, which express the human stearoyl-CoA desaturase-1 isoform (SCD1) exclusively. The Δ5 and Δ9 desaturase activities are indexed by the efficient conversion of [1-¹⁴C]-eicosatrienoic acid (C20:3, cis-8,11,14) to ¹⁴C-arachidonic acid (C20:4, cis-5,8,11,14) and the conversion of [1-¹⁴C]-stearic acid to ¹⁴C-oleic acid (C18:1, cis-9), resp. CP-74006 potently blocks the Δ5D activity with an IC₅₀ value of 20 nM and simplifies the metabolism of [1-¹⁴C]-α-linolenate (C18:3, cis-9,12,15) by accumulating ¹⁴C-eicosatetraenoic acid (C20:4, cis-8,11,14,17) as the major ¹⁴C-eicosatrienoic acid (C20:3, cis-11,14,17) and ¹⁴C-docosatetraenoic acid (C22:4, cis-10,13,16,19) as the minor metabolites through Δ6 desaturation and elongation. This simplified metabolite spectrum enables the delineation of the Δ6D activity by comparing the combined Δ6D/elongase activity index of the ¹⁴C-(C20:4/C18:3) ratio with the corresponding elongation index of the ¹⁴C-(C20:3/C18:3) ratio following compound treatment. SC-26196 and sterculic acid specifically inhibit the Δ6D and Δ9D activities with an IC₅₀ value of 0.1 μM and 0.9 μM, resp. This medium-throughput cell assay provides an efficient tool in the identification of specific desaturase and elongase inhibitors.

Journal of Biomolecular Screening published new progress about 218136-59-5. 218136-59-5 belongs to piperazines, auxiliary class Metabolic Enzyme,D6D, name is 2,2-Diphenyl-5-(4-((pyridin-3-ylmethylene)amino)piperazin-1-yl)pentanenitrile, and the molecular formula is C8H8O2, Related Products of piperazines.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Povedano, Juan Manuel published the artcileA Multipronged Approach Establishes Covalent Modification of β-Tubulin as the Mode of Action of Benzamide Anti-cancer Toxins, Application of 1-(3-Cyanophenyl)piperazine, the publication is Journal of Medicinal Chemistry (2020), 63(22), 14054-14066, database is CAplus and MEDLINE.

A phenotypic high-throughput screen identified a benzamide small mol. with activity against small cell lung cancer cells. A “clickable” benzamide probe was designed that irreversibly bound a single 50 kDa cellular protein, identified by mass spectrometry as β-tubulin. Moreover, the anti-cancer potency of a series of benzamide analogs strongly correlated with probe competition, indicating that β-tubulin was the functional target. Addnl. evidence suggested that benzamides covalently modified Cys239 within the colchicine binding site. Consistent with this mechanism, benzamides impaired growth of microtubules formed with β-tubulin harboring Cys239, but not β₃ tubulin encoding Ser239. We therefore designed an aldehyde-containing analog capable of trapping Ser239 in β₃ tubulin, presumably as a hemiacetal. Using a forward genetics strategy, we identified benzamide-resistant cell lines harboring a Thr238Ala mutation in β-tubulin sufficient to induce compound resistance. The disclosed chem. probes are useful to identify other colchicine site binders, a frequent target of structurally diverse small mols.

Journal of Medicinal Chemistry published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Application of 1-(3-Cyanophenyl)piperazine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Foley, Timothy L. published the artcile4-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide (ML267), a Potent Inhibitor of Bacterial Phosphopantetheinyl Transferase That Attenuates Secondary Metabolism and Thwarts Bacterial Growth, Formula: C11H13N3, the publication is Journal of Medicinal Chemistry (2014), 57(3), 1063-1078, database is CAplus and MEDLINE.

4′-Phosphopantetheinyl transferases (PPTases) catalyze a post-translational modification essential to bacterial cell viability and virulence. We present the discovery and medicinal chem. optimization of 2-pyridinyl-N-(4-aryl)-piperazine-1-carbothioamides, which exhibit submicromolar inhibition of bacterial Sfp-PPTase with no activity toward the human orthologue. Moreover, compounds within this class possess antibacterial activity in the absence of a rapid cytotoxic response in human cells. An advanced analog of this series, ML267 (55), was found to attenuate production of an Sfp-PPTase-dependent metabolite when applied to Bacillus subtilis at sublethal doses. Addnl. testing revealed antibacterial activity against methicillin-resistant Staphylococcus aureus, and chem. genetic studies implicated efflux as a mechanism for resistance in Escherichia coli. Addnl., we highlight the in vitro absorption, distribution, metabolism, and excretion and in vivo pharmacokinetic profiles of compound 55 to further demonstrate the potential utility of this small-mol. inhibitor.

Journal of Medicinal Chemistry published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Formula: C11H13N3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Beiginejad, Hadi published the artcileDependence of mechanisms to thermodynamics in the electrochemical study of different electrophiles in the presence of some sulfur nucleophiles, COA of Formula: C12H16N2O2, the publication is Monatshefte fuer Chemie, database is CAplus.

Abstract: Electrochem. study of different electrophiles in the presence of p-toluenesulfinic acid and 2-mercaptobenzothiazole as sulfur nucleophiles was investigated. Mechanistic study of the electrochem. reactions indicates that the electrochem. oxidation of some species in the presence of the sulfur groups has different mechanisms, but some other species in the presence of both sulfur nucleophiles have the same mechanism. To explain the reason for this difference, the computational study was used. Thermodn. investigation shows that when ΔG_tot of the electrochem. oxidation of products are less than that of initial species, the electrochem. produced species can be oxidized during controlled-potential coulometry. The results of this work indicate that the computational study can be used to justify the reaction mechanisms. Cyclic voltammetry, linear sweep voltammetry, and controlled-potential coulometry were used to obtain the exptl. results. Also, by the use of BP86 level of theory and 6-31 + G(d,p) basis set, the theor. data were obtained.

Monatshefte fuer Chemie published new progress about 67914-60-7. 67914-60-7 belongs to piperazines, auxiliary class Piperazine,Benzene,Phenol,Amide, name is 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, and the molecular formula is C12H16N2O2, COA of Formula: C12H16N2O2.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Roy, Saikat published the artcileStructural and Physicochemical Aspects of Dasatinib Hydrate and Anhydrate Phases, Safety of N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, the publication is Crystal Growth & Design (2012), 12(4), 2122-2126, database is CAplus and MEDLINE.

Crystal structures for the com. monohydrate form and an anhydrate form of dasatinib, an oral anticancer agent, are presented along with characterization by Raman spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric anal. Solubility measurements conducted in water reveal that the anhydrate has dramatically improved solubility compared to the com. hydrate form. Finally, dasatinib is a rare example of a promiscuous solvate former, and the basis for this behavior can now be understood by examining the poor packing efficiency in the unsolvated form.

Crystal Growth & Design published new progress about 863127-77-9. 863127-77-9 belongs to piperazines, auxiliary class TGF-beta/Smad,Bcr-Abl,Natural product, name is N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, and the molecular formula is C22H28ClN7O3S, Safety of N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Kumar, Vivek published the artcileSynthesis and Pharmacological Characterization of Novel trans-Cyclopropylmethyl-Linked Bivalent Ligands That Exhibit Selectivity and Allosteric Pharmacology at the Dopamine D₃ Receptor (D₃R), Safety of 1-(3-Cyanophenyl)piperazine, the publication is Journal of Medicinal Chemistry (2017), 60(4), 1478-1494, database is CAplus and MEDLINE.

The development of bitopic ligands directed toward D₂-like receptors has proven to be of particular interest to improve the selectivity and/or affinity of these ligands and as an approach to modulate and bias their efficacies. The structural similarities between dopamine D₃ receptor (D₃R)-selective mols. that display bitopic or allosteric pharmacol. and those that are simply competitive antagonists are subtle and intriguing. Herein the authors synthesized a series of mols. in which the primary and secondary pharmacophores were derived from the D₃R-selective antagonists SB269,652 and SB277011A whose structural similarity and pharmacol. disparity provided the perfect templates for SAR investigation. Incorporating a trans-cyclopropylmethyl linker between pharmacophores and manipulating linker length resulted in the identification of two bivalent noncompetitive D₃R-selective antagonists, I and II, which further delineates SAR associated with allosterism at D₃R and provides leads toward novel drug development.

Journal of Medicinal Chemistry published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Safety of 1-(3-Cyanophenyl)piperazine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Sun, Aiming published the artcileDiscovering Small-Molecule Estrogen Receptor ¦Á/Coactivator Binding Inhibitors: High-Throughput Screening, Ligand Development, and Models for Enhanced Potency, Product Details of C11H13N3, the publication is ChemMedChem (2011), 6(4), 654-666, database is CAplus and MEDLINE.

Small mols., namely coactivator binding inhibitors (CBIs), that block estrogen signaling by directly inhibiting the interaction of the estrogen receptor (ER) with coactivator proteins act in a fundamentally different way to traditional antagonists, which displace the endogenous ligand estradiol. To complement our prior efforts at CBI discovery by de novo design, we used high-throughput screening (HTS) to identify CBIs of novel structure and subsequently investigated two HTS hits by analog synthesis, finding many compounds with low micromolar potencies in cell-based reporter gene assays. We examined structure-activity trends in both series, using induced-fit computational docking to propose binding poses for these mols. in the coactivator binding groove. Anal. of the structure of the ER-steroid receptor coactivator (SRC) complex suggests that all four hydrophobic residues within the SRC nuclear receptor box sequence are important binding elements. Thus, insufficient water displacement upon binding of the smaller CBIs in the expansive complexation site may be limiting the potency of the compounds in these series, which suggests that higher potency CBIs might be found by screening compound libraries enriched with larger mols.

ChemMedChem published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C10H14O, Product Details of C11H13N3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Nematollahi, Davood published the artcileDifferent strategies in electrochemical synthesis of new mono and di-substituted hydroquinone and benzoquinone, Product Details of C12H16N2O2, the publication is Electrochimica Acta (2014), 310-318, database is CAplus.

Electrochem. syntheses of 2-indolyl-5-arylsulfonyl-p-benzoquinone derivatives were carried out in two successive oxidation steps. The 1st involves the oxidation of hydroquinone, 4-(piperazin-1-yl)-phenol and 1-(4-(4-hydroxyphenyl)-piperazin-1-yl) ethanone in the presence of arylsulfinic acids as nucleophiles. The authors’ voltammetric data indicate that electrochem. generated p-benzoquinone participates in Michael addition reaction with arylsulfinic acids leading to the 2-(arylsulfonyl) benzene-1,4-diols. The 2nd consists of the oxidation of 2-(arylsulfonyl) benzene-1,4-diols in the presence of 1,2-dimethylindole and the formation of 2-indolyl-5-arylsulfonyl-p-benzoquinone derivatives as the final products. A plausible mechanism for the synthesis of 2-indolyl-5-arylsulfonyl-p-benzoquinone derivatives is also presented.

Electrochimica Acta published new progress about 67914-60-7. 67914-60-7 belongs to piperazines, auxiliary class Piperazine,Benzene,Phenol,Amide, name is 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, and the molecular formula is C12H16N2O2, Product Details of C12H16N2O2.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics