Month: February 2023

Virtual screening and biological characterization of novel histone arginine methyltransferase PRMT1 inhibitors was written by Heinke, Ralf;Spannhoff, Astrid;Meier, Rene;Trojer, Patrick;Bauer, Ingo;Jung, Manfred;Sippl, Wolfgang. And the article was included in ChemMedChem in 2009.Reference of 129-74-8 This article mentions the following:

Lysine and arginine methyltransferases participate in the posttranslational modification of histones and regulate key cellular functions. Protein arginine methyltransferase 1 (PRMT1) has been identified as an essential component of mixed lineage leukemia (MLL) oncogenic complexes, revealing its potential as a novel therapeutic target in human cancer. The first potent arginine methyltransferase inhibitors were recently discovered by random- and target-based screening approaches. Herein we report virtual and biol. screening for novel inhibitors of PRMT1. Structure-based virtual screening (VS) of the Chembridge database composed of 328 000 mols. was performed with a combination of ligand- and target-based in silico approaches. Nine inhibitors were identified from the top-scored docking solutions; these were exptl. tested using human PRMT1 and an antibody-based assay with a time-resolved fluorescence readout. Among several aromatic amines, an aliphatic amine and an amide were also found to be active in the micromolar range. In the experiment, the researchers used many compounds, for example, 1-(4-(tert-Butyl)benzyl)-4-((4-chlorophenyl)(phenyl)methyl)piperazine dihydrochloride (cas: 129-74-8Reference of 129-74-8).

1-(4-(tert-Butyl)benzyl)-4-((4-chlorophenyl)(phenyl)methyl)piperazine dihydrochloride (cas: 129-74-8) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 掳C and boils at 125鈥?30 掳C. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Reference of 129-74-8

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Inhibition of Fibroblast Growth Factor Receptor by AZD4547 Protects Against Inflammation in Septic Mice was written by Huang, Yueyue;Wang, Fen;Li, Hao;Xu, ShunYao;Xu, Wenwei;Pan, XiaoJun;Hu, Yufeng;Mao, Lingjie;Qian, Songzan;Pan, Jingye. And the article was included in Inflammation in 2019.Related Products of 1035270-39-3 This article mentions the following:

Sepsis is a life-threatening condition caused by the dysregulated host immune response to infection characterized by excessive secretion of inflammatory factors. AZD4547 is a selective inhibitor of fibroblast growth factor receptors that participates in the inflammatory response. The aim of this study was to investigate the inflammation-targeting effects and related mol. mechanisms of AZD4547 in sepsis using a cecal ligation and puncture model and RAW264.7 macrophages stimulated with lipopolysaccharide. AZD4547 improved the survival of CLP mice and exhibited a robust protective function against lung damage histol. Pretreatment with AZD4547 significantly alleviated the expression of the pro-inflammatory factors IL-1尾, IL-6, TNF-伪, MMP9, and CXCL10 both in vivo and in vitro. In addition, AZD4547 suppressed the proliferative activity of macrophages in lung tissue and RAW264.7 macrophages. In addition, the LPS-induced phosphorylation of key proteins of NF-魏B/MAPK/STAT3 pathways in RAW264.7 macrophages, such as p65, I魏B-伪, Erk1/2, JNK, and STAT3 proteins, could be inhibited by AZD4547 pretreatment. In conclusion, AZD4547 exerts a protective effect against excessive inflammatory damage in septic mice and may have the potential for use as an effective drug for the management of sepsis. In the experiment, the researchers used many compounds, for example, rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3Related Products of 1035270-39-3).

rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Related Products of 1035270-39-3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors was written by Cumming, J. N.;Le, T. X.;Babu, S.;Carroll, C.;Chen, X.;Favreau, L.;Gaspari, P.;Guo, T.;Hobbs, D. W.;Huang, Y.;Iserloh, U.;Kennedy, M. E.;Kuvelkar, R.;Li, G.;Lowrie, J.;McHugh, N. A.;Ozgur, L.;Pan, J.;Parker, E. M.;Saionz, K.;Stamford, A. W.;Strickland, C.;Tadesse, D.;Voigt, J.;Wang, L.;Wu, Y.;Zhang, L.;Zhang, Q.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2008.COA of Formula: C16H22N2O3 This article mentions the following:

Guided by structure-based design two series of potent inhibitors of BACE1, were synthesized and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2′ pocket. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate (cas: 78551-60-7COA of Formula: C16H22N2O3).

tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate (cas: 78551-60-7) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.COA of Formula: C16H22N2O3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Characteristics of drugs evaluated by computational chemistry. (5). Typical antipsychotics was written by Hayano, Taizo;Kishioka, Shiroh;Yamamoto, Hiroyuki;Ikoma, Yoshihisa. And the article was included in Wakayama Igaku in 2005.Synthetic Route of C22H30N4O2S2 This article mentions the following:

Antipsychotics are divided into two types, i.e. typical type and atypical type. Typical type mainly includes phenothiazines and butyrophenones. Risperidone is located on the boundary. We furthermore divide the typical type into umbrella shape and cylindrical shape based on the mol. form. They have the side chain that connect with main ring with characteristic bond angle. Electron d. was high on main ring where HOMO and LUMO localized and low on terminal chain. Statistical anal. showed that there are no significant difference on the electron energies, the dipole moments, the dihedral angles between umbrella shape mols. and cylindrical ones. These results suggested the importance of the Pr group joining to the side chain with main ring. In the experiment, the researchers used many compounds, for example, N,N-Dimethyl-10-(3-(4-methylpiperazin-1-yl)propyl)-10H-phenothiazine-2-sulfonamide (cas: 316-81-4Synthetic Route of C22H30N4O2S2).

N,N-Dimethyl-10-(3-(4-methylpiperazin-1-yl)propyl)-10H-phenothiazine-2-sulfonamide (cas: 316-81-4) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Synthetic Route of C22H30N4O2S2

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Thermal Stability and Utility of Dienes as Protecting Groups for Acrylamides was written by Hooper, Annie R.;Burns, Alexander S.. And the article was included in ACS Medicinal Chemistry Letters in 2022.Category: piperazines This article mentions the following:

Herein, several diene-acrylamide adducts with a range of thermal stabilities toward retro-Diels-Alder deprotection of the acrylamide, enabling this masked functionality to be introduced early in a synthetic route and deprotected in a specific temperature range was reported. Through kinetic studies, solvent and structural trends that impact the stability of trimethylsilyl cyclopentadiene (TMS-CP) acrylamide adducts was identified. TMS-CP protected acrylamides were installed on several amine-containing drugs, whose acrylamides were thermally unveiled (T = 160掳C, time 鈮?1 h) in moderate to high yields. The potential utility of this protection strategy by improving the yield of a base-promoted S_NAr reaction when the acrylamide WAs masked. In the experiment, the researchers used many compounds, for example, 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (cas: 571190-30-2Category: piperazines).

6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (cas: 571190-30-2) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Category: piperazines

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Optimization of quantitative analysis of buclizine hydrochloride using UV spectrophotometry in bulk drug and dosage formulations was written by Siddiqui, Farhan Ahmed;Mirza, Agha Zeeshan;Zuberi, M. Hashim;Qureshi, Faiza. And the article was included in Medicinal Chemistry Research in 2011.Name: 1-(4-(tert-Butyl)benzyl)-4-((4-chlorophenyl)(phenyl)methyl)piperazine dihydrochloride This article mentions the following:

Development and validation of an anal. spectral calibration method to quantify buclizine hydrochloride, which is a piperazine derivative and used as a single active principle in pharmaceutical forms were done. The quantification of buclizine hydrochloride was performed in the wavelength range of 218-226 nm at N = 6. The linear regression equation was constructed using relationship between concentration and absorbance at 218, 220, 222, 224, and 226 nm. The developed method was applied directly and easily to the anal. of the pharmaceutical tablet preparations Mean %RSD was found to be 0.6231% (Longifene tablet 25 mg). The method was completely validated and proven to be rugged. This validated UV spectrophotometric method is potentially useful for a routine laboratory anal. because of its simplicity, rapidity, sensitivity, precision, and accuracy. In the experiment, the researchers used many compounds, for example, 1-(4-(tert-Butyl)benzyl)-4-((4-chlorophenyl)(phenyl)methyl)piperazine dihydrochloride (cas: 129-74-8Name: 1-(4-(tert-Butyl)benzyl)-4-((4-chlorophenyl)(phenyl)methyl)piperazine dihydrochloride).

1-(4-(tert-Butyl)benzyl)-4-((4-chlorophenyl)(phenyl)methyl)piperazine dihydrochloride (cas: 129-74-8) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Name: 1-(4-(tert-Butyl)benzyl)-4-((4-chlorophenyl)(phenyl)methyl)piperazine dihydrochloride

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Integrated Platform for Expedited Synthesis-Purification-Testing of Small Molecule Libraries was written by Baranczak, Aleksandra;Tu, Noah P.;Marjanovic, Jasmina;Searle, Philip A.;Vasudevan, Anil;Djuric, Stevan W.. And the article was included in ACS Medicinal Chemistry Letters in 2017.Recommanded Product: 1-(1,4-Diazepan-1-yl)ethanone This article mentions the following:

The productivity of medicinal chem. programs can be significantly increased through the introduction of automation, leading to shortened discovery cycle times. Herein, the authors describe a platform that consolidates synthesis, purification, quantitation, dissolution, and testing of small mol. libraries. The system was validated through the synthesis and testing of two libraries of binders of polycomb protein EED, and excellent correlation of obtained data with results generated through conventional approaches was observed The fully automated and integrated platform enables batch-supported compound synthesis based on a broad array of chem. transformations with testing in a variety of biochem. assay formats. A library turnaround time of between 24 and 36 h was achieved, and notably, each library synthesis produces sufficient amounts of compounds for further evaluation in secondary assays thereby contributing significantly to the shortening of medicinal chem. discovery cycles. In the experiment, the researchers used many compounds, for example, 1-(1,4-Diazepan-1-yl)ethanone (cas: 61903-11-5Recommanded Product: 1-(1,4-Diazepan-1-yl)ethanone).

1-(1,4-Diazepan-1-yl)ethanone (cas: 61903-11-5) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 掳C and boils at 125鈥?30 掳C. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Recommanded Product: 1-(1,4-Diazepan-1-yl)ethanone

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Systematic profiling of staralog response to acquired drug resistant kinase gatekeeper mutations in targeted cancer therapy was written by Yang, Yuping;Qiu, Yue;Liu, Xu;Liu, Yanhua;Yin, Yaling;Li, Peng. And the article was included in Amino Acids in 2020.Safety of rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide This article mentions the following:

Here, we describe an integrative approach to systematically profile the mol. response of 15 representative Staralogs to 17 kinase gatekeeper mutations in targeted cancer therapy. With the profile we are able to divide gatekeeper mutations into three classes (i.e. classes I, II and III) and to divide Staralogs into two groups (i.e. groups 1 and 2) using heuristic clustering. The class I and II mutations confer consistent sensitivity and resistance for all Staralogs, resp., while the class III mutations address divergent effects on different Staralogs. The mutations to Ile residue can generally reduce Staralog affinity by inducing unfavorable steric hindrance, whereas the mutations to Met and Leu residues would improve Staralog affinity by establishing favorable S路路路p interaction, van der Waals packing and/or hydrophobic contact. The group 1 and 2 Staralogs are primarily determined by carbonyl or hydroxyl substitution state at the position 7 of Staralog core, where points to kinase gatekeeper residue and can thus be directly influenced by gatekeeper mutation. In the experiment, the researchers used many compounds, for example, rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3Safety of rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide).

rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Safety of rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Conformational analysis of an anxiolytic agent: tandospirone in aqueous solution was written by Igarashi, Jun-Etsu;Nishimura, Tamiki;Sunagawa, Makoto. And the article was included in Bioorganic & Medicinal Chemistry Letters in 1997.Application In Synthesis of rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate This article mentions the following:

The conformations of tandospirone citrate (I) and related compounds in aqueous solution have been studied by ¹H NMR, IR experiments and MM calculations The significant contribution to the folded conformer of tandospirone was found in aqueous solution In the experiment, the researchers used many compounds, for example, rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1Application In Synthesis of rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate).

rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 掳C and boils at 125鈥?30 掳C. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Application In Synthesis of rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Discovery and optimization of novel pyrazole-benzimidazole CPL304110 as a potent and selective inhibitor of fibroblast growth factor receptors FGFR (1-3) was written by Yamani, Abdellah;Zdzalik-Bielecka, Daria;Lipner, Joanna;Stanczak, Aleksandra;Piorkowska, Natalia;Stanczak, Paulina Seweryna;Olejkowska, Patrycja;Hucz-Kalitowska, Joanna;Magdycz, Marta;Dzwonek, Karolina;Dubiel, Krzysztof;Lamparska-Przybysz, Monika;Popiel, Delfina;Pieczykolan, Jerzy;Wieczorek, Maciej. And the article was included in European Journal of Medicinal Chemistry in 2021.Synthetic Route of C26H33N5O3 This article mentions the following:

The scaffolds hybridization approach, scaffold-hopping concept, has been employed to synthesize a series of novel pyrazole-benzimidazoles I [R¹ = H, Cl; R² = morpholin-4-yl, 4-methylpiperazin-1-ylcarbonyl, tetrahydropyran-4-ylcarbamoyl, etc.; R³ = H, F]. Compound I [R¹ = R³ = H; R² = 4-methylpiperazin-1-yl] (CPL304110) was identified as a selective and potent pan-FGFR inhibitor for FGFR1, FGFR2, FGFR3 with IC₅₀ of 0.75 nM, 0.50 nM, 3.05 nM resp., and IC₅₀ of 87.90 nM for FGFR4. Due to its favorable pharmacokinetic profile, low toxicity and potent anti-tumor activity in-vivo, this compound I is currently under evaluation in phase I clin. trial for the treatment of bladder, gastric and squamous cell lung cancers (01FGFR2018; NCT04149691). In the experiment, the researchers used many compounds, for example, rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3Synthetic Route of C26H33N5O3).

rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Synthetic Route of C26H33N5O3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics