Month: January 2023

Synthesis and biological activity of novel 1,4-diazepane derivatives as factor Xa inhibitor with potent anticoagulant and antithrombotic activity was written by Koshio, Hiroyuki;Hirayama, Fukushi;Ishihara, Tsukasa;Taniuchi, Yuta;Sato, Kazuo;Sakai-Moritani, Yumiko;Kaku, Seiji;Kawasaki, Tomihisa;Matsumoto, Yuzo;Sakamoto, Shuichi;Tsukamoto, Shin-ichi. And the article was included in Bioorganic & Medicinal Chemistry in 2004.Category: piperazines This article mentions the following:

Factor Xa (fXa) is a serine protease involved in the coagulation cascade, which has received great interest as a potential target for the development of new antithrombotic drugs. Herein the authors report a novel series of fXa inhibitors in which the 1,4-diazepane moiety was designed to interact with the S4 aryl-binding domain of the fXa active site. Compound 13 (YM-96765) showed potent fXa inhibitory activity (IC₅₀ = 6.8 nM) and effective antithrombotic activity without prolonging bleeding time. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6Category: piperazines).

1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6) 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. 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

Benefits of statistical molecular design, covariance analysis, and reference models in QSAR: a case study on acetylcholinesterase was written by Andersson, C. David;Hillgren, J. Mikael;Lindgren, Cecilia;Qian, Weixing;Akfur, Christine;Berg, Lotta;Ekstroem, Fredrik;Linusson, Anna. And the article was included in Journal of Computer-Aided Molecular Design in 2015.Quality Control of tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate This article mentions the following:

Scientific disciplines such as medicinal- and environmental chem., pharmacol., and toxicol. deal with the questions related to the effects small organic compounds exhort on biol. targets and the compounds’ physicochem. properties responsible for these effects. A common strategy in this endeavor is to establish structure-activity relationships (SARs). The aim of this work was to illustrate benefits of performing a statistical mol. design (SMD) and proper statistical anal. of the mols.’ properties before SAR and quant. structure-activity relationship (QSAR) anal. Our SMD followed by synthesis yielded a set of inhibitors of the enzyme acetylcholinesterase (AChE) that had very few inherent dependencies between the substructures in the mols. If such dependencies exist, they cause severe errors in SAR interpretation and predictions by QSAR-models, and leave a set of mols. less suitable for future decision-making. In our study, SAR- and QSAR models could show which mol. sub-structures and physicochem. features that were advantageous for the AChE inhibition. Finally, the QSAR model was used for the prediction of the inhibition of AChE by an external prediction set of mols. The accuracy of these predictions was asserted by statistical significance tests and by comparisons to simple but relevant reference models. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate (cas: 373608-48-1Quality Control of tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate).

tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate (cas: 373608-48-1) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. 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.Quality Control of tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate

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

New antifilarial agents. 1. Epoxy sulfonamides and ethynesulfonamides was written by Brienne, Marie Josephe;Varech, Daniel;Leclercq, Martine;Jacques, Jean;Radembino, Nathalie;Dessalles, Christine;Mahuzier, Georges;Gueyouche, Chantal;Bories, Christian. And the article was included in Journal of Medicinal Chemistry in 1987.SDS of cas: 21867-64-1 This article mentions the following:

Two series of 2-substituted 1,2-epoxyethanesulfonamides I (R = Me, R¹ = Ph, substituted Ph, Me; NR₂ = morpholino, 4-methylpiperazinyl, etc.) and ethynesulfonamides, e.g., R₂NSO₂CCR¹ (II, R₂N = morpholino, 4-methylpiperazinyl, R¹ = Ph) were synthesized and evaluated for their antifilarial activity. Trans-I were stereospecifically prepared by a Darzens reaction between aldehydes and halomethanesulfonamides. Cis-I were obtained from ethynesulfonamides II by semihydrogenation followed by KOCl epoxidation 2-Substituted ethynesulfonamides II were synthesized from appropriate trans-ethensulfonamides by bromination-dehydrobromination. These products, as well as several synthetic intermediates, were evaluated for antifilarial activity against Molinema dessetae either in vivo in its natural host, the rodent Proechimys oris, or in vitro by a new test using cultures of the infective larvae. Most of the trans–I and II bearing a 2-aryl substituent were active in vitro. trans–I (NR₂ = morpholino, NMe₂, 4-methylpiperazinyl; R¹ = Ph, 3,4-Cl₂C₆H₃) and PhCCSO₂NR² (NR² = morpholino) showed marked macrofilaricidal activity in vivo without any microfilaricidal activity. The differences between the in vivo and in vitro results may be due, in part, to the low chem. stability of trans-I. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1SDS of cas: 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. SDS of cas: 21867-64-1

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

Synthesis and antiviral activity evaluation of derivatives of anti-influenza virus inhibitor nucleozin was written by Yan, Zihong;Cai, Yan;Li, Xueqiong;Ding, Xiaoli;Miao, Zhiwei. And the article was included in Huaxue Tongbao in 2018.Synthetic Route of C13H20N4O2 This article mentions the following:

Nucleozin has good inhibitory activity as an inhibitor against influenza virus nucleoprotein. In this paper, we investigate the aromatic ring part which is connected directly with piperazine in the nucleozin mol. structure. A series of nucleozin derivatives were synthesized by palladium catalyzed coupling reaction, and the structure-activity relationship of this part in nucleozin mol. was clarified by detecting the inhibitory activities of the synthesized compounds on influenza virus H1N1. After replacing the chlorine atom in the mol. with a Me group, it was found that the inhibitory activity is significantly improved compared with the prototype mol. nucleozin. This study has a significant meaning in the drug-like improvement of this kind of mol. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8Synthetic Route of C13H20N4O2).

tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Synthetic Route of C13H20N4O2

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

Parallel Optimization of Potency and Pharmacokinetics Leading to the Discovery of a Pyrrole Carboxamide ERK5 Kinase Domain Inhibitor was written by Miller, Duncan C.;Reuillon, Tristan;Molyneux, Lauren;Blackburn, Timothy;Cook, Simon J.;Edwards, Noel;Endicott, Jane A.;Golding, Bernard T.;Griffin, Roger J.;Hardcastle, Ian;Harnor, Suzannah J.;Heptinstall, Amy;Lochhead, Pamela;Martin, Mathew P.;Martin, Nick C.;Myers, Stephanie;Newell, David R.;Noble, Richard A.;Phillips, Nicole;Rigoreau, Laurent;Thomas, Huw;Tucker, Julie A.;Wang, Lan-Zhen;Waring, Michael J.;Wong, Ai-Ching;Wedge, Stephen R.;Noble, Martin E. M.;Cano, Celine. And the article was included in Journal of Medicinal Chemistry in 2022.Name: tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate This article mentions the following:

The nonclassical extracellular signal-related kinase 5 (ERK5) mitogen-activated protein kinase pathway has been implicated in increased cellular proliferation, migration, survival, and angiogenesis; hence, ERK5 inhibition may be an attractive approach for cancer treatment. However, the development of selective ERK5 inhibitors has been challenging. Previously, we described the development of a pyrrole carboxamide high-throughput screening hit into a selective, submicromolar inhibitor of ERK5 kinase activity. Improvement in the ERK5 potency was necessary for the identification of a tool ERK5 inhibitor for target validation studies. Herein, we describe the optimization of this series to identify nanomolar pyrrole carboxamide inhibitors of ERK5 incorporating a basic center, which suffered from poor oral bioavailability. Parallel optimization of potency and in vitro pharmacokinetic parameters led to the identification of a nonbasic pyrazole analog with an optimal balance of ERK5 inhibition and oral exposure. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3Name: tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate).

tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. 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: tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate

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

Novel piperazine based benzamide derivatives as potential anti-glioblastoma agents inhibiting cell proliferation and cell cycle progression was written by Lu, Yingmei;Feng, Yiyue;Li, Zhao;Li, Junfang;Zhang, Honghua;Hu, Xiaoling;Jiang, Weifan;Shi, Tao;Wang, Zhen. And the article was included in European Journal of Medicinal Chemistry in 2022.Recommanded Product: 21867-64-1 This article mentions the following:

Highly efficacious and tolerable agents for the treatment of glioblastoma (GBM), the most common and aggressive primary brain tumor, are urgently needed. Herein, we reveal the design, synthesis and biol. evaluation of several piperazine based benzamide derivatives, which are based on the non-classical isostere principle and combination principle for GBM therapy. After structure-activity relationship (SAR) study, compound L19 was demonstrated as the most promising compound with IC₅₀ values of 0.15 μM, 0.29 μM, 1.25 μM against GBM C6, U87-MG, U251 cells, resp. Moreover, compound L19 could inhibit the proliferation, migration and invasion, as well as induce apoptosis and cell cycle arrest of GBM cell lines in vitro. From mechanism perspective, compound L19 could regulate the cell cycle-related proteins and influence the p16^INK4a-CDK4/6-pRb pathway by western blotting experiment What is worth mentioning is that compound L19 could penetrate the blood-brain barrier (BBB) with an exceptional brain-to-plasma ratio of 1.07 in vivo. Besides, the superior anti-glioblastoma potency in vivo of compound L19 was identified on U87-MG-xenograft model without any apparent host toxicity. Overall, the potential of compound L19 warrants further pre-clin. investigation for GBM therapy. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Recommanded Product: 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. 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.Recommanded Product: 21867-64-1

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

Synthesis of pyrido[3,4-d]pyrimidines by condensation of ethyl 1-benzyl-3-oxopiperidine-4-carboxylate with morpholine-4-carboxamidine was written by Kuznetsov, A. Yu.;Nam, N. L.;Chapyshev, S. V.. And the article was included in Chemistry of Heterocyclic Compounds (New York, NY, United States) in 2007.COA of Formula: C7H16N2 This article mentions the following:

A method has been developed for the synthesis of 4-amino-substituted tetrahydropyridopyrimidines, e.g., I, by condensation of Et 1-benzyl-3-oxopiperidine-4-carboxylate with morpholine-4-carboxamidine followed by sulfonylation with trifluoromethanesulfonic anhydride and amination with secondary amines. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1COA of Formula: C7H16N2).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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.COA of Formula: C7H16N2

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

Identification of pyridazino[4,5-b]indolizines as selective PDE4B inhibitors was written by Donnell, Andrew F.;Dollings, Paul J.;Butera, John A.;Dietrich, Arlene J.;Lipinski, Kerri K.;Ghavami, Afshin;Hirst, Warren D.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2010.Name: tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate This article mentions the following:

Substituted pyridazino[4,5-b]indolizines were identified as potent and selective PDE4B inhibitors. We describe the structure-activity relationships generated around an HTS hit that led to a series of compounds with low nanomolar affinity for PDE4B and high selectivity over the PDE4D subtype. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate (cas: 373608-48-1Name: tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate).

tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate (cas: 373608-48-1) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Name: tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate

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

Chemical Probe Identification Platform for Orphan GPCRs Using Focused Compound Screening: GPR39 as a Case Example was written by Boehm, Markus;Hepworth, David;Loria, Paula M.;Norquay, Lisa D.;Filipski, Kevin J.;Chin, Janice E.;Cameron, Kimberly O.;Brenner, Martin;Bonnette, Peter;Cabral, Shawn;Conn, Edward;Ebner, David C.;Gautreau, Denise;Hadcock, John;Lee, Esther C. Y.;Mathiowetz, Alan M.;Morin, Michelle;Rogers, Lucy;Smith, Aaron;VanVolkenburg, Maria;Carpino, Philip A.. And the article was included in ACS Medicinal Chemistry Letters in 2013.Name: 6-(Piperazin-1-yl)nicotinonitrile This article mentions the following:

Orphan G protein-coupled receptors (oGPCRs) are a class of integral membrane proteins for which endogenous ligands or transmitters have not yet been discovered. Transgenic animal technologies have uncovered potential roles for many of these oGPCRs, providing new targets for the treatment of various diseases. Understanding signaling pathways of oGPCRs and validating these receptors as potential drug targets requires the identification of chem. probe compounds to be used in place of endogenous ligands to interrogate these receptors. A novel chem. probe identification platform was created in which GPCR-focused libraries were screened against sets of oGPCR targets, with a goal of discovering fit-for-purpose chem. probes for the more druggable members of the set. Application of the platform to a set of oGPCRs resulted in the discovery of the first reported small mol. agonists for GPR39, a receptor implicated in the regulation of insulin secretion and preservation of beta cells in the pancreas. Compound 1 stimulated intracellular calcium mobilization in recombinant and native cells in a GPR39-specific manner but did not potentiate glucose-stimulated insulin secretion in human islet preparations In the experiment, the researchers used many compounds, for example, 6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0Name: 6-(Piperazin-1-yl)nicotinonitrile).

6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125–130 °C. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Name: 6-(Piperazin-1-yl)nicotinonitrile

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

Confocal Fluorescence Detection Expanded to UV Excitation: The First Continuous Fluorimetric Assay of Human Steroid Sulfatase in Nanoliter Volume was written by Billich, Andreas;Bilban, Melitta;Meisner, Nicole-Claudia;Nussbaumer, Peter;Neubauer, Andreas;Jaeger, Stefan;Auer, Manfred. And the article was included in Assay and Drug Development Technologies in 2004.Reference of 162046-66-4 This article mentions the following:

Steroid sulfatase is an enzyme that currently enjoys considerable interest as a potential drug target in the treatment of estrogen- and androgen-dependent diseases, in particular breast cancer. We have purified human steroid sulfatase to apparent homogeneity from recombinant Chinese hamster ovary cells, and we established an assay with a new fluorogenic substrate, 3,4-benzocoumarin-7-O-sulfate (1). Substrate 1 features a Km value of 22.5 μM, which is close to the value for the natural substrate dehydroepiandrosterone sulfate (26 μM) and much lower than the K_m values of other synthetic substrates (276-736 μM). Importantly, the cleavage of substrate 1 can be monitored continuously during the enzymic cleavage, since a change in fluorescence intensity is detectable at the pH where the enzyme is active; in contrast, all other synthetic substrates described so far require alkalization to reveal a measurable absorbance or fluorescence signal. The adaptation of the assay to the 96-well format allows continuous monitoring of multiple wells in a microplate fluorescence reader. Applications of the assay for the determination of IC₅₀ and K_i values of novel steroid sulfatase inhibitors are presented. Most importantly the assay was transferred to the nanoscale format (1-μl assay volume) in 2080-well plates with confocal fluorescence detection. This miniaturization will permit screening with a min. throughput of 20,000 compounds per day. The system presented demonstrates that the confocal detection platform used for nanoscreening can be successfully adapted to assays for which conventional UV dyes like coumarins are necessary. This strongly broadens the application range of confocal readers in drug screening. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Reference of 162046-66-4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Reference of 162046-66-4

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