Category: piperazines

Jeitany, Maya published the artcileNovel carfilzomib-based combinations as potential therapeutic strategies for liposarcomas, Computed Properties of 218136-59-5, the publication is Cellular and Molecular Life Sciences (2021), 78(4), 1837-1851, database is CAplus and MEDLINE.

Proteasome inhibitors, such as bortezomib and carfilzomib, have shown efficacy in anti-cancer therapy in hematol. diseases but not in solid cancers. Here, we found that liposarcomas (LPS) are susceptible to proteasome inhibition, and identified drugs that synergize with carfilzomib, such as selinexor, an inhibitor of XPO1-mediated nuclear export. Through quant. nuclear protein profiling and phospho-kinase arrays, we identified potential mode of actions of this combination, including interference with ribosome biogenesis and inhibition of pro-survival kinase PRAS40. Furthermore, by assessing global protein levels changes, FADS2, a key enzyme regulating fatty acids synthesis, was found down-regulated after proteasome inhibition. Interestingly, SC26196, an inhibitor of FADS2, synergized with carfilzomib. Finally, to identify further combinational options, we performed high-throughput drug screening and uncovered novel drug interactions with carfilzomib. For instance, cyclosporin A a known immunosuppressive agent enhanced carfilzomibs efficacy in vitro and in vivo. Altogether, these results demonstrate that carfilzomib and its combinations could be repurposed for LPS clin. management.

Cellular and Molecular Life Sciences 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 C27H29N5, Computed Properties of 218136-59-5.

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

Nencini, Arianna published the artcileStructure-activity relationship and properties optimization of a series of Quinazoline-2,4-diones as inhibitors of the canonical Wnt pathway, Application In Synthesis of 71260-16-7, the publication is European Journal of Medicinal Chemistry (2015), 526-545, database is CAplus and MEDLINE.

Wnt signaling pathway plays a critical role in numerous cellular processes, including tumor initiation, proliferation, invasion/infiltration, metastasis formation and resistance to chemotherapy. In a drug discovery project aimed at the identification of inhibitors of the canonical Wnt pathway, we selected a series of quinazoline 2,4-diones as starting point for the therapeutic treatment of glioblastoma multiforme. Despite of poor physico-chem. properties of hit compound (I), our medicinal chem. effort allowed the discovery and characterization of lead compound (SEN461; II), with improved ADME profile, good bioavailability and active in vitro and in vivo in glioblastoma, gastric and sarcoma tumors.

European Journal of Medicinal Chemistry published new progress about 71260-16-7. 71260-16-7 belongs to piperazines, auxiliary class Piperazine, name is 2-Methyl-1-(piperazin-1-yl)propan-1-one, and the molecular formula is C8H16N2O, Application In Synthesis of 71260-16-7.

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

Baltus, Christine B. published the artcileMicrowave-mediated Suzuki-Miyaura cross-couplings of thioether- and ortho-substituted methylphenylboronic acid esters, SDS of cas: 1012785-48-6, the publication is Synlett (2012), 23(17), 2477-2480, database is CAplus.

Hiterto unsuccessful cross-couplings of ortho-substituted or thioether-substituted methylphenylboronates have now been achieved, under microwave conditions, enabling the synthesis of a library of novel biaryls. Tetrakis(triphenylphosphine)palladium and various bases, for example, sodium carbonate or cesium fluoride, were found to mediate the crucial C-C bond-forming cross-coupling reaction. E.g., in presence of tetrakis(triphenylphosphine)palladium and CsF, reaction of thioether-substituted methylphenylboronate (I) and 4-BrC₆H₄NO₂ gave 91% II.

Synlett published new progress about 1012785-48-6. 1012785-48-6 belongs to piperazines, auxiliary class Boronic acid and ester, name is tert-Butyl 4-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)piperazine-1-carboxylate, and the molecular formula is C22H35BN2O4, SDS of cas: 1012785-48-6.

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

Laskowska, Anna K. published the artcileOpioid Tripeptides Hybridized with trans-1-Cinnamylpiperazine as Proliferation Inhibitors of Pancreatic Cancer Cells in Two- and Three-Dimensional in vitro Models, Application In Synthesis of 87179-40-6, the publication is ChemMedChem (2017), 12(19), 1637-1644, database is CAplus and MEDLINE.

According to the World Health Organization, the mortality rate among patients with pancreatic cancer will increase in the upcoming years. Gemcitabine is the first choice for treatment of pancreatic malignancy, but increasing resistance to this drug is decreasing its overall efficacy. Studies on new therapies that target metabolic pathways, growth factor inhibitors, and tumor stroma or tumor stem cells are currently underway in many research groups. Herein the authors report the bioactive properties (cytotoxicity and hemolytic activity) of synthetic peptidomimetics containing an opioid tripeptide fragment (Tyr-R¹-R²-; where R¹ is D-Ala or D-Thr, and R² is Phe or Trp) hybridized with trans-1-cinnamylpiperazine. These compounds are stable in plasma up to 96 h and exhibit low hemotoxicity and good inhibitory effects on cancer cell growth in two- and three-dimensional in vitro models of pancreatic cancer.

ChemMedChem published new progress about 87179-40-6. 87179-40-6 belongs to piperazines, auxiliary class Benzenes, name is (E)-1-Cinnamylpiperazine, and the molecular formula is C13H18N2, Application In Synthesis of 87179-40-6.

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

Hu, Feng published the artcile¹⁸F-labeled radiotracers for in vivo imaging of DREADD with positron emission tomography, Synthetic Route of 67914-60-7, the publication is European Journal of Medicinal Chemistry (2021), 113047, database is CAplus and MEDLINE.

Designer Receptors Exclusively Activated by Designer Drugs (DREADD) are a preclin. chemogenetic approach with clin. potential for various disorders. In vivo visualization of DREADDs has been achieved with positron emission tomog. (PET) using ¹¹C radiotracers. The objective of this study was to develop DREADD radiotracers labeled with ¹⁸F for a longer isotope half-life. A series of non-radioactive fluorinated analogs of clozapine with a wide range of in vitro binding affinities for the hM3Dq and hM4Di DREADD receptors has been synthesized for PET. Compound [¹⁸F]7b was radiolabeled via a modified ¹⁸F-deoxyfluorination protocol with a com. ruthenium reagent. [¹⁸F]7b demonstrated encouraging PET imaging properties in a DREADD hM3Dq transgenic mouse model, whereas the radiotracer uptake in the wild type mouse brain was low. [¹⁸F]7b is a promising long-lived alternative to the DREADD radiotracers [¹¹C]clozapine ([¹¹C]CLZ) and [¹¹C]deschloroclozapine ([¹¹C]DCZ).

European Journal of Medicinal Chemistry 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, Synthetic Route of 67914-60-7.

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

Fujimoto, Shota published the artcileIndocyanine green-labeled dasatinib as a new fluorescent probe for molecular imaging of gastrointestinal stromal tumors, SDS of cas: 863127-77-9, the publication is Journal of Gastroenterology and Hepatology (2021), 36(5), 1253-1262, database is CAplus and MEDLINE.

It is difficult to differentiate gastrointestinal stromal tumors (GISTs) from other subepithelial lesions under gastrointestinal endoscopy. Because most GISTs express tyrosine kinase receptor c-KIT, fluorescence-labeled c-KIT-specific tyrosine kinase inhibitors seem to be useful agents for mol. imaging of GIST. We aimed to develop a near-IR fluorescent imaging technol. for GIST targeting c-KIT using the novel fluorescent probe indocyanine green-labeled dasatinib (ICG-dasatinib) and to investigate the antitumor effect of ICG-dasatinib on GIST cells. Indocyanine green-labeled dasatinib was synthesized by labeling linker-induced dasatinib with ICG derivative 3-indocyanine-green-acyl-1,3-thiazolidine-2-thione. Human GIST cell lines GIST-T1 and GIST-882M were incubated with ICG-dasatinib and observed by fluorescent microscopy. GIST cells were incubated with ICG-dasatinib, unlabeled dasatinib, or imatinib, and cell viabilities were evaluated. S.c. GIST model mice or orthotopic GIST model rats were i.v. injected with ICG-dasatinib and observed using an IVIS Spectrum. Strong fluorescent signals of ICG-dasatinib were observed in both GIST cell lines in vitro. IC₅₀ values for ICG-dasatinib, unlabeled dasatinib, and imatinib were 13.9, 1.17, and 16.2 nM in GIST-T1 and 26.6, 3.63, and 47.6 nM in GIST-882M cells, resp. ICG-dasatinib accumulated in s.c. xenografts in mice. Fluorescent signals were also observed in liver and gallbladder, indicating biliary excretion; however, fluorescence intensity of tumors was significantly higher than that of intestine after washing. Strong fluorescent signals were observed in orthotopic xenografts through the covering normal mucosa in rats. Indocyanine green-labeled dasatinib could visualize GIST cells and xenografted tumors. The antitumor effect of ICG-dasatinib was preserved to the same degree as imatinib.

Journal of Gastroenterology and Hepatology 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, SDS of cas: 863127-77-9.

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

Yadav, M. R. published the artcileDesign and synthesis of 6,7-dimethoxyquinazoline analogs as multi-targeted ligands for α₁– and AII-receptors antagonism, SDS of cas: 178928-58-0, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(13), 3959-3966, database is CAplus and MEDLINE.

Multiple-targeted ligands can have certain advantages for the management of hypertension which has multiple controls. Mols. with dual bioactivities are available in literature for treating metabolic disorders like diabetes, hypertension and hypercholesterolemia. After scrutinizing the SAR of prazosin-type α₁-blockers and AII-antagonists it was planned to develop dual α₁– and AII-antagonists. Five series of quinazoline derivatives were synthesized and evaluated as dual α₁– and AII-antagonists on rat aortic strips for the blockade of known α₁– and AII-agonist mediated contractions. Many compounds showed balanced activity on both the receptors but compound (22) was the most active derivative having higher antagonistic activity on both the receptors. In the in vivo experiments the chosen compound (22) was slightly less active than prazosin but was equipotent to losartan. These findings shed a new light on the structural requirements for both α₁– and AII-receptor antagonists.

Bioorganic & Medicinal Chemistry Letters 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 C44H28ClFeN4, SDS of cas: 178928-58-0.

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