Month: November 2022

Deng, Yongqi published the artcileDiscovery of Novel, Dual Mechanism ERK Inhibitors by Affinity Selection Screening of an Inactive Kinase, COA of Formula: C16H18N2, the publication is Journal of Medicinal Chemistry (2014), 57(21), 8817-8826, database is CAplus and MEDLINE.

An affinity-based mass spectrometry screening technol. was used to identify novel binders to both nonphosphorylated and phosphorylated ERK2. Screening of inactive ERK2 identified a pyrrolidine analog 1 that bound to both nonphosphorylated and phosphorylated ERK2 and inhibited ERK2 kinase activity. Chem. optimization identified compound 4 as a novel, potent, and highly selective ERK1,2 inhibitor which not only demonstrated inhibition of phosphorylation of ERK substrate p90RSK but also demonstrated inhibition of ERK1,2 phosphorylation on the activation loop. X-ray cocrystallog. revealed that upon binding of compound 4 to ERK2, Tyr34 undergoes a rotation (flip) along with a shift in the poly-Gly rich loop to create a new binding pocket into which 4 can bind. This new binding mode represents a novel mechanism by which high affinity ATP-competitive compounds may achieve excellent kinase selectivity.

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, COA of Formula: C16H18N2.

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

Itsumi, Momoe published the artcileProfile of androgen receptor activators identified using high-throughput screen, Recommanded Product: 2-((4-(4-Chlorophenyl)piperazin-1-yl)methyl)pyrazolo[1,5-a]pyridine, the publication is Andrologia (2021), 53(1), e13856, database is CAplus and MEDLINE.

In this study using distinct system, effectors on dopamine signalling were identified as candidates that prominently increase AR activity. Then, this study suggested novel function on AR signalling in several compounds, which may be useful or harmful in organs where AR signalling play a role. In conclusion, various candidates for AR activation were identified using high-throughput screening.

Andrologia published new progress about 337972-47-1. 337972-47-1 belongs to piperazines, auxiliary class Inhibitor, name is 2-((4-(4-Chlorophenyl)piperazin-1-yl)methyl)pyrazolo[1,5-a]pyridine, and the molecular formula is C18H19ClN4, Recommanded Product: 2-((4-(4-Chlorophenyl)piperazin-1-yl)methyl)pyrazolo[1,5-a]pyridine.

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

Wilson, Daniel J. published the artcileA continuous fluorescence displacement assay for BioA: An enzyme involved in biotin biosynthesis, Product Details of C20H17ClN4O3, the publication is Analytical Biochemistry (2011), 416(1), 27-38, database is CAplus and MEDLINE.

Cofactor biosynthetic pathways represent a rich source of potential antibiotic targets. The second step in biotin biosynthesis is performed by BioA, a pyridoxal 5′-phosphate (PLP)-dependent enzyme. This enzyme has been confirmed as a candidate target in Mycobacterium tuberculosis; however, the current bioassay used to measure BioA activity is cumbersome and low throughput. Here we describe the design, development, and optimization of a continuous coupled fluorescence displacement assay to measure BioA activity. In this coupled assay, BioD converts the product of the BioA-catalyzed reaction into dethiobiotin, which is subsequently detected by displacement of a fluorescently labeled dethiobiotin probe from streptavidin. The assay was further adapted to a high-throughput screening format and validated against the LOPAC¹²⁸⁰ library.

Analytical Biochemistry 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 C6H8N2, Product Details of C20H17ClN4O3.

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

Raajaraman, BR. published the artcileInvestigation on 1-Acetyl-4-(4-hydroxyphenyl) piperazine an anti-fungal drug by spectroscopic, quantum chemical computations and molecular docking studies, Application of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, the publication is Journal of Molecular Structure (2018), 583-595, database is CAplus.

The title compound, 1-acetyl-4-(4-hydroxyphenyl)piperazine (1A4HP) has been examined by FT-Raman, FT-IR, ¹HNMR, ¹³CNMR and UV-Visible spectra range. By using the d. functional theory (DFT) by the method B3LYP and basis set 6-311++G(d,p) the optimized figure of 1A4HP, the vibrational modes, the IR penetration intensities and the working of Raman scattering were estimated The optimized mol. figure obtained by the DFT method and its bond length and bond angle computed values are same as the XRD exptl. values. AIM topol. anal. was done on the mol. The HOMO and LUMO energy results show that good exchange of charge happened inside the mol. NBO method was applied to study donor-acceptor interactions. ¹H and ¹³C chem. shift of NMR were estimated using the type gauge-independent AO (GIAO) and the results are related to the exptl. values. The hyperpolarizability computation shows the 1A4HP has very good NLO property. The anal. of Fukui function and Mol. electrostatic potential (MEP) studies were done. The essential thermodn. characters (entropy, enthalpy and heat capacity) of the 1A4HP estimated at various temperatures The best ligand-protein interactions are done by mol. docking with the various antifungal proteins and the ligand 1A4HP.

Journal of Molecular Structure 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 of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone.

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

Bachovchin, Kelly A. published the artcileImprovement of aqueous solubility of lapatinib-derived analogues: identification of a quinolinimine lead for human African trypanosomiasis drug development, Synthetic Route of 914610-39-2, the publication is Journal of Medicinal Chemistry (2019), 62(2), 665-687, database is CAplus and MEDLINE.

Lapatinib, an approved epidermal growth factor receptor inhibitor, was explored as a starting point for the synthesis of new hits against Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). Previous work culminated in I, which was part of a series typically associated with poor aqueous solubility In this report, we present various medicinal chem. strategies that were used to increase the aqueous solubility and improve the physicochem. profile without sacrificing antitrypanosomal potency. To rank trypanocidal hits, a new assay (summarized in a cytocidal effective concentration (CEC₅₀)) was established, as part of the lead selection process. Increasing the sp³ carbon content of I resulted in II (0.19 μM EC₅₀ against T. brucei and 990 μM aqueous solubility). Further chem. exploration of II yielded III, a trypanocidal quinolinimine (EC₅₀: 0.013 μM; aqueous solubility: 880 μM; and CEC₅₀: 0.18 μM). Compound III reduced parasitemia 10⁹ fold in trypanosome-infected mice; it is an advanced lead for HAT drug development.

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, Synthetic Route of 914610-39-2.

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

Hamamoto, Tomoyuki published the artcileVisualization and analysis of adverse reactions of molecularly targeted anticancer agents using the self-organizing map (SOM), Product Details of C22H28ClN7O3S, the publication is Yakugaku Zasshi (2014), 134(10), 1069-1080, database is CAplus and MEDLINE.

Molecularly targeted anticancer agents cause a variety of adverse reactions compared with conventional anticancer agents because of their unique mechanisms of action. Sources of drug information such as package inserts (PIs) provide primarily document-based and numerical information. Therefore it is not easy to obtain a complete picture of drugs with similar effects, or to understand differences among drugs. In this study we used the self-organizing map (SOM) technique to visualize the adverse reactions indicated on PIs of 23 molecularly targeted anticancer agents as of March 2013. In both the presence/absence version and the frequency version, SOM was divided into domains according to mechanism of action, antibody drug or low-mol. weight drug, and mol. target. The component planes of the 753 adverse reaction items in the frequency version enabled us to grasp all available information and differences among the drugs. In some component planes in the presence/absence version, an adverse reaction that had not been reported for a drug but had already been reported for its proximally positioned drug (s) as of March 2013, was found to be reported thereafter by the Drug Safety Update (DSU) or the Adverse Event Report Search System “CzeekV,” which is based on FDA Adverse Event Reporting System (FAERS). Our results suggest that visualization of the adverse reactions of molecularly targeted anticancer agents by the SOM technique is useful not only to acquire all available information and differences among drugs, but also to predict the appearance of adverse reactions.

Yakugaku Zasshi 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, Product Details of C22H28ClN7O3S.

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

Tanoury, Gerald J. published the artcilePd-catalyzed aminations of aryltriazolones: effective synthesis of hydroxyitraconazole enantiomers, Formula: C12H16N2O2, the publication is Tetrahedron Letters (1998), 39(38), 6845-6848, database is CAplus.

A palladium-catalyzed amination of triazolone I by piperazine II was used as the key step in an efficient synthesis of highly enantiomerically pure hydroxyitraconazole (III). II (>99% ee) was prepared by reaction of an achiral phenol precursor with the corresponding dioxolyl tosylate (>99% ee).

Tetrahedron 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 C8H7NO4, Formula: C12H16N2O2.

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

Jiang, Jie published the artcileA_2B Adenosine Receptor Antagonists with Picomolar Potency, Synthetic Route of 67914-60-7, the publication is Journal of Medicinal Chemistry (2019), 62(8), 4032-4055, database is CAplus and MEDLINE.

The A2B adenosine receptor (A2BAR) was proposed as a novel target for the (immuno)therapy of cancer since A2BAR blockade results in antiproliferative, anti-angiogenic, anti-metastatic, and immuno-stimulatory effects. In this study, we explored the structure-activity relationships of xanthin-8-yl-benzenesulfonamides mainly by introducing a variety of linkers and substituents attached to the sulfonamide residue. A new, convergent strategy was established which facilitated the synthesis of the target compounds Many of the new compounds exhibited subnanomolar affinity for the A2BAR combined with high selectivity. Functional groups were introduced which will allow the attachment of dyes and other reporter groups. 8-(4-((4-(4-Bromophenyl)piperazin-1-yl)sulfonyl)phenyl)-1-propylxanthine (34, PSB-1901) was the most potent A2B-antagonist (Ki 0.0835 nM, KB 0.0598 nM, human A2BAR) with >10,000-fold selectivity vs. all other AR subtypes. It was similarly potent and selective at the mouse A2BAR, making it a promising tool for preclin. studies. Computational studies predicted halogen bonding to contribute to the outstanding potency of 34.

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

Kurokawa, Mikio published the artcileSynthesis and biological activity of 11-[4-(cinnamyl)-1-piperazinyl]-6,11-dihydrodibenz[b,e]oxepin derivatives, potential agents for the treatment of cerebrovascular disorders, Category: piperazines, the publication is Chemical & Pharmaceutical Bulletin (1991), 39(10), 2564-73, database is CAplus and MEDLINE.

A series of 11-[4-(cinnamyl)-1-piperazinyl]-6,11-dihydrodibenz[b,e]oxepins and related compounds were synthesized and evaluated for their protective activities against complete ischemia, normobaric hypoxia, lipid peroxidation and convulsion. Structure-activity relationship studies of this series led to the finding of (E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]oxepin-11-yl)-4-(3-phenyl-2-propenyl)piperazine dimaleate (I), AJ-3941, with the most appropriate property for combined pharmacol. activities. I also shows an inhibitory effect against cerebral edema as well when orally given to rats.

Chemical & Pharmaceutical Bulletin 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

Guerrera, F. published the artcileSynthesis of 1-alkyl-3-dialkylaminoalkylamino[1]benzothieno[2,3-b]pyrazin-2(1H)-ones and their ability to antagonize KCl-induced contractions, HPLC of Formula: 87179-40-6, the publication is European Journal of Medicinal Chemistry (1996), 31(7-8), 607-613, database is CAplus.

A series of 1-alkyl-3-dialkylaminoalkylamino[1]benzothieno[2,3-b]pyrazin-2(1H)-ones was prepared Some of these compounds showed appreciable inhibition towards KCl-induced contractions in isolated rat aortic rings. Although this activity appears at higher concentrations than with caroverine, used as reference standard, this new tricyclic system could be considered as a nucleus with potential calcium antagonistic activity.

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, HPLC of Formula: 87179-40-6.

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