Month: November 2022

Hopper, Allen T. published the artcileDiscovery of selective Toxoplasma gondii dihydrofolate reductase inhibitors for the treatment of toxoplasmosis, Related Products of piperazines, the publication is Journal of Medicinal Chemistry (2019), 62(3), 1562-1576, database is CAplus and MEDLINE.

A safer treatment for toxoplasmosis would be achieved by improving the selectivity and potency of dihydrofolate reductase (DHFR) inhibitors, such as pyrimethamine I, for Toxoplasma gondii DHFR (TgDHFR) relative to human DHFR (hDHFR). We previously reported on the identification of meta-biphenyl analog II, designed by in silico modeling of key differences in the binding pocket between TgDHFR and hDHFR. II improves TgDHFR selectivity 6.6-fold and potency 16-fold relative to I. Here, we report on the optimization and structure-activity relationships of this arylpiperazine series leading to the discovery of 5-(4-(3-(2-methoxypyrimidin-5-yl)phenyl)piperazin-1-yl)pyrimidine-2,4-diamine III. III has a TgDHFR IC₅₀ of 1.57 ± 0.11 nM and a hDHFR to TgDHFR selectivity ratio of 196, making it 89-fold more potent and 16-fold more selective than I. III was highly effective in control of acute infection by highly virulent strains of T. gondii in the murine model, and it possesses the best combination of selectivity, potency, and prerequisite drug-like properties to advance into IND-enabling, preclin. development.

Journal of Medicinal Chemistry 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, Related Products of piperazines.

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

Dezi, Cristina published the artcileMultistructure 3D-QSAR Studies on a Series of Conformationally Constrained Butyrophenones Docked into a New Homology Model of the 5-HT_2A Receptor, Synthetic Route of 945953-41-3, the publication is Journal of Medicinal Chemistry (2007), 50(14), 3242-3255, database is CAplus and MEDLINE.

The present study is part of a long-term research project aiming to gain insight into the mechanism of action of atypical antipsychotics. Here we describe a 3D-QSAR study carried out on a series of butyrophenones with affinity for the serotonin-2A receptor, aligned by docking into the binding site of a receptor model. The series studied has two peculiarities: (i) all the compounds have a chiral center and can be represented by two enantiomeric structures, and (ii) many of the structures can bind the receptor in two alternative orientations, posing the problem of how to select a single representative structure for every compound We have used an original solution consisting of the simultaneous use of multiple structures, representing different configurations, binding conformations, and positions. The final model showed good statistical quality (n = 426, r² = 0.84, q²_LOO = 0.81) and its interpretation provided useful information, not obtainable from the simple inspection of the ligand-receptor complexes.

Journal of Medicinal Chemistry published new progress about 945953-41-3. 945953-41-3 belongs to piperazines, auxiliary class Piperazine,Amide,Aldehyde, name is tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, and the molecular formula is C11H20N2O3, Synthetic Route of 945953-41-3.

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

Juen, Ludovic published the artcileNew Inhibitor Targeting Signal Transducer and Activator of Transcription 5 (STAT5) Signaling in Myeloid Leukemias, COA of Formula: C17H27BN2O4S, the publication is Journal of Medicinal Chemistry (2017), 60(14), 6119-6136, database is CAplus and MEDLINE.

Signal Transducer and Activator of Transcription 5 (STAT5) are crucial effectors of tyrosine kinase oncogenes in myeloid leukemias. Inhibition of STAT5 would contribute to reducing the survival of leukemic cells and also tackling their chemoresistance. In a first screening experiment, the authors identified hit 13 (I) as able to inhibit STAT5 phosphorylation and leukemic cell growth. The synthesis of 18 analogs of 13 allowed the authors to identify one compound, 17f (II), as having the most potent antileukemic effect. Compound 17f inhibited the growth of acute and chronic myeloid leukemia cells and phosphorylation and transcriptional activity of STAT5. Importantly, 17f had minimal effects on bone marrow stromal cells that play vital functions in the microenvironment of hematopoietic and leukemic cells. The authors also demonstrated that 17f inhibits STAT5 but not STAT3, AKT or Erk1/2 phosphorylation. These results suggest that 17f might be a new lead mol. targeting STAT5 signaling in myeloid leukemias.

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, COA of Formula: C17H27BN2O4S.

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

Young, Reuben S. E. published the artcileApocryphal FADS2 activity promotes fatty acid diversification in cancer, Name: 2,2-Diphenyl-5-(4-((pyridin-3-ylmethylene)amino)piperazin-1-yl)pentanenitrile, the publication is Cell Reports (2021), 34(6), 108738, database is CAplus and MEDLINE.

Canonical fatty acid metabolism describes specific enzyme-substrate interactions that result in products with well-defined chain lengths, degree(s), and positions of unsaturation Deep profiling of lipids across a range of prostate cancer cell lines reveals a variety of fatty acids with unusual site(s) of unsaturation that are not described by canonical pathways. The structure and abundance of these unusual lipids correlate with changes in desaturase expression and are strong indicators of cellular phenotype. Gene silencing and stable isotope tracing demonstrate that direct Δ6 and Δ8 desaturation of 14:0 (myristic), 16:0 (palmitic), and 18:0 (stearic) acids by FADS2 generate new families of unsaturated fatty acids (including n-8, n-10, and n-12) that have rarely-if ever-been reported in human-derived cells. Isomer-resolved lipidomics reveals the selective incorporation of these unusual fatty acids into complex structural lipids and identifies their presence in cancer tissues, indicating functional roles in membrane structure and signaling.

Cell Reports 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 C11H10N4, Name: 2,2-Diphenyl-5-(4-((pyridin-3-ylmethylene)amino)piperazin-1-yl)pentanenitrile.

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

Mghandef, Marwa published the artcile1-(4-Hydroxyphenyl)piperazine-1,4-diium tetrachloridocobalt(II) monohydrate, Name: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, the publication is Acta Crystallographica, Section E: Structure Reports Online (2014), 70(2), m75, database is CAplus and MEDLINE.

The asym. unit of the title inorganic-organic hybrid compound, (C₁₀H₁₆N₂O)[CoCl₄]·H₂O, consists of a tetrahedral [CoCl₄]^2- anion, together with a [C₁₀H₁₈N₂O]²⁺ cation and a water mol. Crystal cohesion is achieved through N-H···Cl, O-H···Cl and N-H···O hydrogen bonds between organic cations, inorganic anions and the water mols., building up a three-dimensional network.

Acta Crystallographica, Section E: Structure Reports Online 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, Name: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone.

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

Gerpe, Alejandra published the artcileNaftifine-analogues as anti-Trypanosoma cruzi agents, Category: piperazines, the publication is European Journal of Medicinal Chemistry (2010), 45(6), 2154-2164, database is CAplus and MEDLINE.

Chagas disease represents a relevant health problem in Central and South America. The first line of treatment is Nifurtimox and Benznidazole which have a great deal of disadvantages; this demands the rapid generation of therapeutic alternatives. Based in our research on aza-thiaheterocycles as anti-Trypanosoma cruzi agents we identified pharmacophores that act through oxidative stress. Here, we describe the synthesis and the activity of new containing bioactive-heterocycles analogs of naftifine as potential T. cruzi membrane sterol biosynthesis inhibitors. Benzimidazole 1,3-dioxides and quinoxaline 1,4-dioxides displayed excellent parasite/mammal selectivity indexes. Anal. of the free sterols from parasite incubated with the compounds showed that any of them are able to accumulate squalene suggesting that in the anti-T. cruzi mechanism of action is not involved the inhibition of sterol biosynthesis. Some derivatives were also tested as antifungal agents. The results obtained in the present work open potential therapeutic possibilities of new compounds for these infectious diseases.

European Journal of Medicinal Chemistry 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, Category: piperazines.

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

Faudone, Giuseppe published the artcilePropranolol Activates the Orphan Nuclear Receptor TLX to Counteract Proliferation and Migration of Glioblastoma Cells, Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, the publication is Journal of Medicinal Chemistry (2021), 64(12), 8727-8738, database is CAplus and MEDLINE.

The ligand-sensing transcription factor tailless homolog (TLX, NR2E1) is an essential regulator of neuronal stem cell homeostasis with appealing therapeutic potential in neurodegenerative diseases and central nervous system tumors. However, knowledge on TLX ligands is scarce, providing an obstacle to target validation and medicinal chem. To discover TLX ligands, we have profiled a drug fragment collection for TLX modulation and identified several structurally diverse agonists and inverse agonists of the nuclear receptor. Propranolol evolved as the strongest TLX agonist and promoted TLX-regulated gene expression in human glioblastoma cells. Structure-activity relationship elucidation of propranolol as a TLX ligand yielded a structurally related neg. control compound In functional cellular experiments, we observed an ability of propranolol to counteract glioblastoma cell proliferation and migration, while the neg. control had no effect. Our results provide a collection of TLX modulators as initial chem. tools and set of lead compounds and support therapeutic potential of TLX modulation in glioblastoma.

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

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

Couchman, L. published the artcileAn automated method for the measurement of a range of tyrosine kinase inhibitors in human plasma or serum using turbulent flow liquid chromatography-tandem mass spectrometry, Synthetic Route of 863127-77-9, the publication is Analytical and Bioanalytical Chemistry (2012), 403(6), 1685-1695, database is CAplus and MEDLINE.

Tyrosine kinase inhibitors (TKIs) are used to treat a number of cancers, including chronic myeloid leukemia and hepatocellular carcinoma. Therapeutic drug monitoring (TDM) may be indicated to (1) monitor adherence, (2) guide dosage, and (3) minimise the risk of drug-drug interactions and dose-related toxicity. Online, automated sample preparation provided by TurboFlow technol. (ThermoFisher Scientific) in conjunction with the sensitivity and selectivity of tandem mass spectrometry (MS/MS) detection may be applied to the anal. of single drugs and metabolites. We report the use of TurboFlow LC-MS/MS for the anal. of nine TKIs and metabolites (imatinib, N-desmethylimatinib, dasatinib, nilotinib, erlotinib, gefitinib, lapatinib, sorafenib, sunitinib) in human plasma or serum for TDM purposes. An Aria Transcend TLX-II system coupled with a TSQ Vantage was used. Samples (50 μL) were vortex mixed with internal standard solution (150 μL imatinib-D₈, gefitinib-D₈, sunitinib-D₁₀, and nilotinib-¹³C₂¹⁵N₂ in acetonitrile) and, after centrifugation 100 μL supernatant were injected directly onto a 50 × 0.5-mm Cyclone TurboFlow column. Analytes were focussed onto a 50 × 2.1-mm (3 μm) Hypersil GOLD anal. column and eluted with an acetonitrile/water gradient. Analytes were monitored in selected reaction monitoring mode (pos. APCI). Total anal. time was 7 min without multiplexing. Calibration was linear (R² > 0.99) for all analytes. Inter- and intra-assay precision (in percent relative standard deviation, RSD) was <11 % and accuracy 89-117 % for all analytes. No matrix effects were observed This method is suitable for high-throughput TDM in patients undergoing chronic therapy with TKIs and has been utilized in the anal. of clin. samples.

Analytical and Bioanalytical Chemistry 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, Synthetic Route of 863127-77-9.

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

Sardana, Malvika published the artcileVisible-Light-Enabled Aminocarbonylation of Unactivated Alkyl Iodides with Stoichiometric Carbon Monoxide for Application on Late-Stage Carbon Isotope Labeling, Application In Synthesis of 87179-40-6, the publication is Journal of Organic Chemistry (2019), 84(24), 16076-16085, database is CAplus and MEDLINE.

A visible-light-mediated late-stage aminocarbonylation of unactivated alkyl iodides with stoichiometric amounts of carbon monoxide is presented. The method provides a mild, one-step route to [carbonyl-^13/14C] alkyl amides, thereby reducing radioactive waste, and handling of radioactive materials. Easily accessible and low-cost equipment and a palladium catalyst were successfully used for the synthesis of a wide range of alkyl amides.

Journal of Organic Chemistry 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

Leopoldo, Marcello published the artcileStructure-Affinity Relationship Study on N-(1,2,3,4-Tetrahydronaphthalen-1-yl)-4-Aryl-1-Piperazinealkylamides, a New Class of 5-Hydroxytryptamine₇ Receptor Agents, Application of 1-(3-Cyanophenyl)piperazine, the publication is Journal of Medicinal Chemistry (2004), 47(26), 6616-6624, database is CAplus and MEDLINE.

A series of N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinealkylamides I (n = 3-5, R¹ = OMe, H, R² = OMe, CN, Ac, SMe, OH, etc.) was prepared and their affinity for serotonin (5-hydroxytryptamine, 5-HT) 5-HT₇, 5-HT_1A, and 5-HT_2A receptors was measured by in vitro binding assays. In relation to 5-HT₇ receptor affinity, receptor binding studies indicated that (i) the optimal alkyl chain length was five methylenes, (ii) an unsubstituted 1,2,3,4-tetrahydronaphthalenyl nucleus was preferred, and (iii) the substitution pattern of the aryl ring linked to the piperazine ring played a crucial role. Several compound with high affinity for 5-HT₇ receptors were identified. Among them, piperazinehexanamides I [n = 5, R¹ = H, R² = 2-OMe (II), 2-Ac (III), 2-SMe (IV), 2-OH (V), and 2-Me (VI)] were assayed for the 5-HT₇ receptor-mediated relaxation of substance P-induced guinea pig ileum contraction. Compounds II, IV, and VI behaved as full agonists and compound III as a partial agonist, whereas derivative V acted as an antagonist. Among the compounds presented here, it emerged that IV was identified as a potent 5-HT₇ receptor agonist (K_i = 0.22 nM, EC₅₀ = 2.56 μM), endowed with selectivity over 5-HT_1A and 5-HT_2A receptors (200-fold and >1000-fold, resp.).

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