Month: November 2022

Cheung, Leanna published the artcileIdentification of new MRP4 inhibitors from a library of FDA approved drugs using a high-throughput bioluminescence screen, Recommanded Product: (4-Chlorophenyl)(4-(8-nitroquinolin-5-yl)piperazin-1-yl)methanone, the publication is Biochemical Pharmacology (Amsterdam, Netherlands) (2015), 93(3), 380-388, database is CAplus and MEDLINE.

Multidrug resistance protein 4 (MRP4) effluxes a wide variety of drugs and endogenous signaling mols. from cells and was proposed as an attractive therapeutic target in several solid tumors, including neuroblastoma and colorectal cancer. MRP4 also regulates the pharmacokinetics of its drug substrates and its absence can increase their tissue penetration. We observed that MRP4 can efflux the bioluminescence substrate D-luciferin, and exploited this phenomenon to develop a robust, high throughput, live cell-based bioluminescent screen to identify new MRP4 inhibitors. We applied this screen to a combined library of 3600 compounds, all of which were either FDA-approved drugs or bioactive compounds with defined mechanisms of action. From the primary screen, 36 compounds effectively inhibited MRP4 (>4-fold increase in bioluminescence), with inhibitors of receptor tyrosine kinases and phosphodiesterases highly over-represented. Selected compounds were tested for their ability to sensitize MRP4-overexpressing cell lines to the MRP4 substrate drugs 6-mercaptopurine and SN-38, with sensitization up to 6.5-fold with the ryanodine receptor antagonist dantrolene. These newly identified MRP4 inhibitors are readily available and are either established drugs or well-characterized bioactive compounds As such, they should be immediately useful as investigative tools, and suitable for testing both in vitro and in vivo.

Biochemical Pharmacology (Amsterdam, Netherlands) published new progress about 115687-05-3. 115687-05-3 belongs to piperazines, auxiliary class Epigenetics,Sirtuin, name is (4-Chlorophenyl)(4-(8-nitroquinolin-5-yl)piperazin-1-yl)methanone, and the molecular formula is C20H17ClN4O3, Recommanded Product: (4-Chlorophenyl)(4-(8-nitroquinolin-5-yl)piperazin-1-yl)methanone.

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

Yang, Shyh-Ming published the artcileDiscovery of NCT-501, a Potent and Selective Theophylline-Based Inhibitor of Aldehyde Dehydrogenase 1A1 (ALDH1A1), Category: piperazines, the publication is Journal of Medicinal Chemistry (2015), 58(15), 5967-5978, database is CAplus and MEDLINE.

Aldehyde dehydrogenases (ALDHs) metabolize reactive aldehydes and possess important physiol. and toxicol. functions in areas such as CNS, metabolic disorders, and cancers. Increased ALDH (e.g., ALDH1A1) gene expression and catalytic activity are vital biomarkers in a number of malignancies and cancer stem cells, highlighting the need for the identification and development of small mol. ALDH inhibitors. A new series of theophylline-based analogs as potent ALDH1A1 inhibitors is described. The optimization of hits identified from a quant. high throughput screening (qHTS) campaign led to analogs with improved potency and early ADME properties. This chemotype exhibits highly selective inhibition against ALDH1A1 over ALDH3A1, ALDH1B1, and ALDH2 isoenzymes as well as other dehydrogenases such as HPGD and HSD17β4. Moreover, the pharmacokinetic evaluation of selected analog (NCT-501) is also highlighted.

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 C12H10FeO4, Category: piperazines.

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

Xu, Feng published the artcileSynthesis, antitumor evaluation and molecular docking studies of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives, COA of Formula: C8H16N2O, the publication is Bioorganic & Medicinal Chemistry Letters (2016), 26(13), 3042-3047, database is CAplus and MEDLINE.

A series of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives were synthesized and evaluated for their antitumor activities. These compounds exhibited potent antiproliferative activities against MCF-7, Bewo and HL-60 cells and c-Met kinase inhibitory activities. Three compounds were highly effective against MCF-7, Bewo and HL-60 cells with IC₅₀ values in 1.09-2.24 μM. Mol. docking was further performed to study the inhibitor-c-Met kinase interactions, and compound 4-([1,2,4]Triazolo[4,3-b][1,2,4,5]tetrazin-3-yl)morpholine was potently bound to the c-Met kinase with three hydrogen bonds. The further research on acute toxicity and in vivo antitumor activity of compound 4-([1,2,4]Triazolo[4,3-b][1,2,4,5]tetrazin-3-yl)morpholine to ICR (Institute of Cancer Research) mice were carried out, and found 4-([1,2,4]Triazolo[4,3-b][1,2,4,5]tetrazin-3-yl)morpholine with a certain toxicity but good efficacy in vivo. Based on the preliminary results, compound 4-([1,2,4]Triazolo[4,3-b][1,2,4,5]tetrazin-3-yl)morpholine with potent c-Met kinase inhibitory activity may be a potential anticancer agent.

Bioorganic & Medicinal Chemistry Letters 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 C25H23NO4, COA of Formula: C8H16N2O.

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

Chen, Xing published the artcileDiscovery and In Vivo Anti-inflammatory Activity Evaluation of a Novel Non-peptidyl Non-covalent Cathepsin C Inhibitor, Application of 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, the publication is Journal of Medicinal Chemistry (2021), 64(16), 11857-11885, database is CAplus and MEDLINE.

Cathepsin C (Cat C) participates in inflammation and immune regulation by affecting the activation of neutrophil serine proteases (NSPs). Therefore, cathepsin C is an attractive target for treatment of NSP-related inflammatory diseases. Here, the complete discovery process of the first potent “non-peptidyl non-covalent cathepsin C inhibitor” was described with hit finding, structure optimization, and lead discovery. Starting with hit 14, structure-based optimization and structure-activity relationship study were comprehensively carried out, and lead compound 54 was discovered as a potent drug-like cathepsin C inhibitor both in vivo and in vitro. Also, compound 54 (with cathepsin C Enz IC₅₀ = 57.4 nM) exhibited effective anti-inflammatory activity in an animal model of chronic obstructive pulmonary disease. These results confirmed that the non-peptidyl and non-covalent derivative could be used as an effective cathepsin C inhibitor and encouraged us to continue further drug discovery on the basis of this finding.

Journal of Medicinal Chemistry published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C10H16N4, Application of 6-(4-Methylpiperazin-1-yl)pyridin-3-amine.

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

Tang, Haifeng published the artcileDesign and synthesis of a new class of malonyl-CoA decarboxylase inhibitors with anti-obesity and anti-diabetic activities, COA of Formula: C11H13N3, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(20), 6088-6092, database is CAplus and MEDLINE.

A new series of thiazole-substituted 1,1,1,3,3,3-hexafluoro-2-propanols, e.g. I, were prepared and evaluated as malonyl-CoA decarboxylase (MCD) inhibitors. Key analogs caused dose-dependent decreases in food intake and body weight in obese mice. Acute treatment with these compounds also led to a drop in elevated blood glucose in a murine model of type II diabetes.

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 C19H14Cl2, COA of Formula: C11H13N3.

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

Liu, Chaomei published the artcileSynthesis and antifungal activities of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-substituted group-2-propanols, Application In Synthesis of 67914-60-7, the publication is Zhongguo Yaowu Huaxue Zazhi (2004), 14(3), 129-133, database is CAplus.

The title compounds 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-(4-alkyloxyphenylpiperazin-1-yl)-2-propanols, e.g. I, and 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-substituted sulfur ether-2-propanols, e.g. II, were synthesized through the reaction of an intermediate epoxide and 4-alkyloxyphenylpiperazines or substituted sulfur alcs. The structures were confirmed by the elementary anal., ¹H-MR and IR spectra. MIC₈₀ of all the title compounds were determined by the method recommended by the National Committee for Clin. Laboratory Standards (NCCLS) using the RPMI1640 test medium. The results of the preliminary antifungal test show that all the title compounds exhibited potent antifungal activities to a certain extent. The antifungal activity of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-(4-alkyloxyphenylpiperazin-1-yl)-2-propanols was more potent than that of 1-(1H,1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-substituted sulfur ether-2-propanols in vitro. The antifungal activities of the four compounds in 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-(4-alkyloxyphenylpiperazin-1-yl)-2-propanols are more potent than that of fluconazole or equal to that of ketoconazole in vitro.

Zhongguo Yaowu Huaxue Zazhi 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, Application In Synthesis of 67914-60-7.

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

Guo, Jing published the artcileDiscovery of novel TrkA allosteric inhibitors: Structure-based virtual screening, biological evaluation and preliminary SAR studies, Related Products of piperazines, the publication is European Journal of Medicinal Chemistry (2022), 114022, database is CAplus and MEDLINE.

Tropomyosin receptor kinases A (TrkA) is a potential therapeutic target for the treatment of numerous tumor types and chronic pain. However, most of the reported TrkA inhibitors are ATP competitive pan-Trks inhibitors that lack subtype selectivity. A selective TrkA inhibitor may provide valuable therapeutic benefits. Here, we described the discovery of novel TrkA allosteric inhibitors by structure-based virtual screening. A promising hit (I, TrkA cell IC₅₀ = 3.32 μM) was selected for further studies. The binding free energy between TrkA and I was calculated In addition, the preliminary structure-activity relationship (SAR) studies with I were investigated. The results suggest that I can be used as a starting point for development of TrkA allosteric inhibitors.

European Journal of Medicinal Chemistry published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C10H16N4, Related Products of piperazines.

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

Guo, Dong published the artcileBinding Kinetics of ZM241385 Derivatives at the Human Adenosine A_2A Receptor, Application of 1-Biphenyl-4-yl-piperazine, the publication is ChemMedChem (2014), 9(4), 752-761, database is CAplus and MEDLINE.

Classical drug design and development rely mostly on affinity- or potency-driven structure-activity relationships (SAR). Thus far, a given compound’s binding kinetics have been largely ignored, the importance of which is now being increasingly recognized. In the present study, we performed an extensive structure-kinetics relationship (SKR) study in addition to a traditional SAR anal. at the adenosine A_2A receptor (A_2AR). The ensemble of 24 A_2AR compounds, all triazolotriazine derivatives resembling the prototypic antagonist ZM241385 (4-(2-((7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino)ethyl)phenol), displayed only minor differences in affinity, although they varied substantially in their dissociation rates from the receptor. We believe that such a combination of SKR and SAR analyses, as we have done with the A_2AR, will have general importance for the superfamily of G protein-coupled receptors, as it can serve as a new strategy to tailor the interaction between ligand and receptor.

ChemMedChem published new progress about 180698-19-5. 180698-19-5 belongs to piperazines, auxiliary class Piperazine,Benzene, name is 1-Biphenyl-4-yl-piperazine, and the molecular formula is C16H18N2, Application of 1-Biphenyl-4-yl-piperazine.

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

Zhao, Liang-Liang published the artcileOrtho-Selective Hydrogen Isotope Exchange of Phenols and Benzyl Alcohols by Mesoionic Carbene-Iridium Catalyst, Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, the publication is Organic Letters (2021), 23(23), 9297-9302, database is CAplus and MEDLINE.

Hydrogen isotope exchange reactions of phenols and benzyl alcs. was achieved by a mesoionic carbene-iridium catalyst with high ortho selectivity and high functional group tolerance. Control experiments indicated that acetate is crucial to realize the ortho selectivity, whereas d. functional theory calculations supported an outer-sphere direction with hydrogen bonding between acetate and the hydroxyl group.

Organic Letters 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 C39H35N5O8, Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone.

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

Devine, William published the artcileProtozoan parasite growth inhibitors discovered by cross-screening yield potent scaffolds for lead discovery, Formula: C17H27BN2O4S, the publication is Journal of Medicinal Chemistry (2015), 58(14), 5522-5537, database is CAplus and MEDLINE.

Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have an estimated combined burden of over 87 million disability-adjusted life years. New drugs are needed for each of these diseases. Building on the previous identification of NEU-617 as a potent and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), the authors have now tested this class of analogs against other protozoal species: T. cruzi (Chagas disease), Leishmania major (cutaneous leishmaniasis), and Plasmodium falciparum (malaria). Based on hits identified in this screening campaign, the authors describe the preparation of several replacements for the quinazoline scaffold and report these inhibitors’ biol. activities against these parasites. In doing this, the authors have identified several potent proliferation inhibitors for each pathogen, such as NEU-924, I, for T. cruzi and NEU-1017, II, for L. major and P. falciparum.

Journal of Medicinal Chemistry published new progress about 914610-39-2. 914610-39-2 belongs to piperazines, auxiliary class Piperazine,Boronic acid and ester,Sulfamide,Benzene,Piperazine,Boronate Esters,Boronic acid and ester,, name is 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine, and the molecular formula is C17H27BN2O4S, Formula: C17H27BN2O4S.

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