Heterocyclic Building Blocks-piperidine

Synergistic suppression of a disintegrin acurhagin-C in combination with AZD4547 and reparixin on terminating development for human osteosarcoma MG-63 cell was written by Shih, Chun-Ho;Chiang, Tin-Bin;Wang, Wen-Jeng. And the article was included in Biochemical and Biophysical Research Communications in 2017.Application of 1035270-39-3 This article mentions the following:

Current therapies available for the treatment of human osteosarcoma, an aggressive bone tumor, are insufficient. To examine an alternative approach of integrin-based anti-osteosacoma strategy, acurhagin-C, a Glu-Cys-Asp (ECD)-disintegrin, was isolated and evaluated for its application in combination with two potent inhibitors of basic fibroblast growth factor (bFGF) and interleukin-8 (IL-8). The investigation of human osteosarcoma MG-63 cells pre-incubated with a FGF receptor-1 (FGFR-1) blocker AZD4547, a CXC-chemokine receptor-1/-2 (CXCR1/2) antagonist reparixin, and acurhagin-C via two given modes of separation and combination was executed. Detected by flow cytometry, integrins-α2/-α5/-αv/-β1, FGFR-1, CXCR1 and CXCR2 constitutively express on the resting membrane. However, bFGF/IL-8-activated MG-63 cells only statistically enhanced the surface exposure of integrins-α5/-β1, FGFR-1 and CXCR2. In activated MG-63 cells, acurhagin-C targeting integrin-α5 not only might potentiate the inhibitory effect of AZD4547 and reparixin on the surface expression of integrin-α5, FGFR-1 and CXCR2, but also acurhagin-C used alone remained effectively to diminish the surface exposure of those targeted receptors. Hence, a complicated crosstalk mechanism should be involved in the membrane interactions. Furthermore, co-administration of acurhagin-C with AZD4547 and reparixin also showed to have the synergistic suppression toward cell proliferation and the gene expression of matrix metalloproteinase-2. Also, the administration of three-in-one mode could nearly abrogate the cellular attachment onto collagen-IV- and fibronectin-coated wells, as well as penetration into Matrigel-barrier. These data supported an ECD-disintegrin acurhagin-C targeting integrin-α5 upon combined used with AZD4547 and reparixin may become a promising therapeutic approach for attenuating osteosarcoma development. 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: 1035270-39-3Application 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. Piperazine belongs to the family of medicines called anthelmintics. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Application of 1035270-39-3

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

Starting dose selection of palbociclib in Chinese patients with breast cancer based on population kinetic-pharmacodynamic model of neutropenia was written by Jian, Weizhe;Xue, Junsheng;Yao, Qingyu;Chen, Rong;Yao, Ye;Wang, Mopei;Zhou, Tianyan. And the article was included in Cancer Chemotherapy and Pharmacology in 2022.Application In Synthesis of 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one This article mentions the following:

Abstract: Neutropenia is the most common adverse event (AE) of palbociclib, an oral CDK4/6 inhibitor for breast cancer. Neutropenia increases the risk of infection and is even life threatening. Asian patients generally suffer more severe neutropenia from palbociclib treatment, but the label does not recommend a reduction in the starting dose for Asian patients. Therefore, the study aimed to explore the exposure-response (E-R) relationship in Chinese patients and preliminarily generate a scale for starting dose selection of palbociclib in Chinese patients. After comparing the kinetic-pharmacodynamic (K-PD) and the pharmacokinetic/pharmacodynamic (PK/PD) model, a semi-mechanistic K-PD model was selected and developed on the basis of real-world data from 28 patients with breast cancer to describe the time course of longitudinal absolute neutrophil counts (ANC). The longitudinal ANC data were well described by the population K-PD model with reasonable parameters: mean transit time (MTT) of 198 h, feedback parameter (γ) of 0.317, baseline ANC level (Circ₀) of 3.36 x 10⁹ L^-1, drug effect coefficient (k_d) of 0.0349, and drug effect power (β) of 0.383. No covariate was included in the final model. The model showed that palbociclib dose-dependently reduced ANC levels in a Chinese population, and lower baseline ANC level was associated with more severe neutropenia. The dose selection scale suggested that palbociclib 125 mg daily was appropriate for Chinese patients with Circ₀ higher than 3.75 x 10⁹ L^-1. In summary, the K-PD model of palbociclib well described the longitudinal ANC in Chinese patients. Besides, the starting dose selection scale may provide reference for clinicians during individualized therapy. 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: 571190-30-2Application In Synthesis of 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one).

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. 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. 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 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one

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

Impulse control disorders by dopamine partial agonists: a pharmacovigilance-pharmacodynamic assessment through the FDA adverse event reporting system was written by Fusaroli, Michele;Raschi, Emanuel;Giunchi, Valentina;Menchetti, Marco;Giorgini, Roberto Rimondini;De Ponti, Fabrizio;Poluzzi, Elisabetta. And the article was included in International Journal of Neuropsychopharmacology in 2022.Product Details of 913611-97-9 This article mentions the following:

Background: The dopaminergic partial agonism of the so-called third-generation antipsychotics (TGAs; aripiprazole, brexpiprazole, cariprazine) is hypothesized to cause impulse control disorders (ICDs). Relevant warnings by the Food and Drug Administration (FDA) were posted on aripiprazole (2016) and brexpiprazole (2018). Our study investigated the FDA Adverse Event Reporting System and the pharmacodynamic CHEMBL database to further characterize TGA-induced ICDs. Methods: We downloaded and pre-processed the FDA Adverse Event Reporting System up to Dec. 2020. We adapted Bradford Hill criteria to assess each TGA’s -and secondarily other antipsychotics’-causal role in inducing ICDs (pathol. gambling, compulsive shopping, hyperphagia, hypersexuality), accounting for literature and disproportionality. ICD clin. features were analyzed, and their pathogenesis was investigated using receptor affinities. Results: A total of 2708 reports of TGA-related ICDs were found, primarily recording aripiprazole (2545 reports, 94%) among the drugs, and gambling (2018 reports, 75%) among the events. Bradford-Hill criteria displayed evidence for a causal role of each TGA consistent across subpopulations and when correcting for biases. Significant disproportionalities also emerged for lurasidone with compulsive shopping, hyperphagia, and hypersexuality, and olanzapine and ziprasidone with hyperphagia. Time to onset varied between days and years, and pos. dechallenge was observed in 20% of cases. Frequently, co-reported events were economic (50%), obsessive-compulsive (44%), and emotional conditions (34%). 5-Hydroxytryptamine receptor type 1a agonism emerged as an addnl. plausible pathogenetic mechanism. Conclusions: We detected an association between TGAs and ICDs and identified a new signal for lurasidone. ICD characteristics are behavior specific and may heavily impact on life. The role of 5-Hydroxytryptamine receptor type 1a agonism should be further explored. In the experiment, the researchers used many compounds, for example, 7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one (cas: 913611-97-9Product Details of 913611-97-9).

7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one (cas: 913611-97-9) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Product Details of 913611-97-9

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

A simple blue fluorescent probe to detect Hg²⁺ in semiaqueous environment by intramolecular charge transfer mechanism was written by Srivastava, Priyanka;Ali, Rashid;Razi, Syed S.;Shahid, Mohammad;Patnaik, Satyakam;Misra, Arvind. And the article was included in Tetrahedron Letters in 2013.Product Details of 142-64-3 This article mentions the following:

An efficient intramol. charge transfer fluorescent probe bridging benzhydryl moiety and dansyl fluorophore through piperazine unit was synthesized and characterized. The photophys. behavior of synthesized probe was analyzed in the presence of different cations in aqueous acetonitrile solution The probe showed sensitivity to detect Hg²⁺ ion selectively over other tested cations at 20 nM level. The probable mode of binding of Hg²⁺ through the nitrogen and oxygen atoms of piperazine and dansyl was established by spectral data anal. In the experiment, the researchers used many compounds, for example, Piperazine Dihydrochloride (cas: 142-64-3Product Details of 142-64-3).

Piperazine Dihydrochloride (cas: 142-64-3) 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. Product Details of 142-64-3

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

Synthesis and SAR of novel oxazolidinones: Discovery of ranbezolid was written by Das, Biswajit;Rudra, Sonali;Yadav, Ajay;Ray, Abhijit;Rao, A. V. S. Raja;Srinivas, A. S. S. V.;Soni, Ajay;Saini, Suman;Shukla, Shalini;Pandya, Manisha;Bhateja, Pragya;Malhotra, Sunita;Mathur, Tarun;Arora, S. K.;Rattan, Ashok;Mehta, Anita. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2005.Related Products of 154590-34-8 This article mentions the following:

Novel oxazolidinones, e.g. I (R = H, CHO, CO₂H, HON:CH, CN, Cl, etc.), containing a number of substituted five-membered heterocycles attached to the piperazinyl-phenyl-oxazolidinone core of eperezolid, were synthesized. Further, the piperazine ring of the core was replaced by other diamino-heterocycles. These modifications led to several compounds with potent activity against a spectrum of resistant and susceptible Gram-pos. organisms, along with the identification of ranbezolid I (R = O₂N) (RBx 7644) as a clin. candidate. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate (cas: 154590-34-8Related Products of 154590-34-8).

tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate (cas: 154590-34-8) 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. 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.Related Products of 154590-34-8

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

Peptidomimetics as protein arginine deiminase 4 (PAD4) inhibitors was written by Trabocchi, Andrea;Pala, Nicolino;Krimmelbein, Ilga;Menchi, Gloria;Guarna, Antonio;Sechi, Mario;Dreker, Tobias;Scozzafava, Andrea;Supuran, Claudiu T.;Carta, Fabrizio. And the article was included in Journal of Enzyme Inhibition and Medicinal Chemistry in 2015.Category: piperazines This article mentions the following:

The protein arginine deiminase 4 (PAD4) is a calcium-dependent enzyme, which catalyzes the irreversible conversion of peptidyl-arginines into peptidyl-citrullines and plays an important role in several diseases such as in the rheumatoid arthritis, multiple sclerosis, Alzheimer’s disease, Creutzfeldt-Jakob’s disease and cancer. In this study, the authors report the inhibition profiles and computational docking toward the PAD4 enzyme of a series of 1,2,3-triazole peptidomimetic-based derivatives incorporating the β-phenylalanine and guanidine scaffolds. Several effective, low micromolar PAD4 inhibitors are reported in this study. In the experiment, the researchers used many compounds, for example, 1-(But-3-yn-1-yl)piperazine (cas: 911398-04-4Category: piperazines).

1-(But-3-yn-1-yl)piperazine (cas: 911398-04-4) 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. 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

Synthesis and structure-activity relationship study of 8-hydroxyquinoline-derived Mannich bases as anticancer agents was written by Shaw, Arthur Y.;Chang, Chun-Yi;Hsu, Mei-Yuan;Lu, Pei-Jung;Yang, Chia-Ning;Chen, Hui-Ling;Lo, Cheng-Wei;Shiau, Chung-Wai;Chern, Ming-Kai. And the article was included in European Journal of Medicinal Chemistry in 2010.Application In Synthesis of 1-(Phenylsulfonyl)piperazine This article mentions the following:

To continue our early study on the structural modifications of clioquinol, more 8-hydroxyquinoline-derived Mannich bases were synthesized and examined for growth-inhibitory effect. Taken Mannich base I as our lead compound, upon replacement of either sulfonyl group with methylene group or piperazine ring with ethylenediamine group resulted in an appreciable increase in potency. On the other hand, as 8-hydroxyquinoline was replaced with phenol, 3-hydroxypyridine and 1-naphthol, a dramatic decrease in activity was observed, indicating that 8-hydroxyquinoline is a crucial scaffold for activity. Further 3D-QSAR anal. on HeLa cells revealed that both steric and electronic effects contributed equally to growth inhibition. Taken together, the structure-activity relationships obtained from both in vitro data and CoMFA model warrant a valuable reference for further study. In the experiment, the researchers used many compounds, for example, 1-(Phenylsulfonyl)piperazine (cas: 14172-55-5Application In Synthesis of 1-(Phenylsulfonyl)piperazine).

1-(Phenylsulfonyl)piperazine (cas: 14172-55-5) 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 is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Application In Synthesis of 1-(Phenylsulfonyl)piperazine

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

Acid-base titrimetric assay of hydroxyzine dihydrochloride in pharmaceutical samples was written by Rajendraprasad, Nagaraju;Basavaiah, Kanakapura;Vinay, Basavaiah Kanakapura. And the article was included in Chemical Industry & Chemical Engineering Quarterly in 2010.Computed Properties of C21H29Cl3N2O2 This article mentions the following:

Two simple titrimetric methods have been developed for the determination of hydroxyzine dihydrochloride (HDH) in pure form and in tablets. The principle of the methods are simple acid-base reactions in which the hydrochloride content of the drug was determined by titrating with an aqueous standardized NaOH solution either visually using phenolphthalein as indicator (method A) or potentiometrically using glass-calomel electrode system (method B). The methods were applicable over the range of 2-20 mg HDH. The procedures were also applied for the determination of HDH in its dosage forms and the results were found to be in good agreement with those obtained by the reference method. The precision, expressed by intra-day and inter-day relative standard deviation values, was satisfactory (RSD ≤ 2.76%). The accuracy was satisfactory as well (RE ≤ 2.67%). Excipients used as additives in pharmaceutical formulations did not interfere in the proposed procedures as shown by the recovery study via a standard addition technique with recovery percentage in the range 97.48-106.3% with a standard deviation of 1.76-3.42 %. In the experiment, the researchers used many compounds, for example, 2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol dihydrochloride (cas: 2192-20-3Computed Properties of C21H29Cl3N2O2).

2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol dihydrochloride (cas: 2192-20-3) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. 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.Computed Properties of C21H29Cl3N2O2

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

Autophagy inhibition improves the cytotoxic effects of receptor tyrosine kinase inhibitors was written by Aveic, Sanja;Pantile, Marcella;Polo, Pierfrancesco;Sidarovich, Viktoryia;De Mariano, Marilena;Quattrone, Alessandro;Longo, Luca;Tonini, Gian Paolo. And the article was included in Cancer Cell International in 2018.Application of 1341200-45-0 This article mentions the following:

Autophagy activation is among the possible obstacles for good efficacy of the therapy with RTKi. Under different treatment conditions we measured autophagic flux using immunoblot and immunofluorescence assays. Death induction was validated by trypan blue exclusion assay and FACS anal. (calcein-AM/propidium iodide). The NB cell lines SH-SY5Y and Kelly were used for the in vitro study. In order to define whether autophagy might be a limiting factor for the efficacy of RTKi in NB cells, we firstly checked its activation following the treatment with several RTKi. Next, we investigated the possibility to increase their therapeutic efficiency by combining RTKi with autophagy blocking agents in vitro. We exploited the effectiveness of three RTKi either alone or in combination with autophagy inhibitors (Chloroquine-CQ and Spautin-1). We demonstrated that autophagy induction was drug-dependent, and that its inhibition increased the anti-tumor activity of a single RTKi unevenly. We observed that the combined use of blocking agents which impair late autophagy events, such as CQ, and RTKi can be more effective with respect to the use of RTKi alone. In the present report, we assessed the conditions under which autophagy is activated during the use of different RTKi currently in the pre-clin. evaluation for NB. We summarized the achievements of combined RTK/autophagy inhibitors treatment as a promising approach to enhance the efficacy of RTKi in impairing tumor cells viability. In the experiment, the researchers used many compounds, for example, 2-((5-Chloro-2-((4-((4-methylpiperazin-1-yl)methyl)phenyl)amino)pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide (cas: 1341200-45-0Application of 1341200-45-0).

2-((5-Chloro-2-((4-((4-methylpiperazin-1-yl)methyl)phenyl)amino)pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide (cas: 1341200-45-0) 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.Application of 1341200-45-0

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

Proton nuclear magnetic resonance spectroscopy (NMR) methods for determining the purity of reference drug standards and illicit forensic drug seizures was written by Hays, Patrick A.. And the article was included in Journal of Forensic Sciences in 2005.Reference of 2192-20-3 This article mentions the following:

A rapid, sensitive, accurate, precise, reproducible, and versatile method for determining the purity of reference drug standards and the routine anal. of illicit drugs and adulterants using proton (¹H) NMR Spectroscopy is presented. The methodol. uses a weighed sample dissolved in a deuterated solvent or solvent mixture containing a high purity internal standard The NMR experiment employs 8 scans using a 45 s delay and 90° pulse. In the determination of purity of reference standards, the number of quant. determinations available is equal to the number of peak groups that are baseline resolved. The relative standard deviation (RSD) of these signals is usually <1% for pure standards, and the results agree well with other purity determining methods. This method can also aid in the determination of correct mol. weight for standards containing an unknown number of waters of hydration or an unknown number of acids per drug in salts. Because the molar response for the hydrogen nucleus is 1 for all compounds, and since no separation media are used, only one linearity study is required to test a probe. In the presented study, the linearity of the NMR probe was determined using methamphetamine HCl dissolved in deuterium oxide (D₂O) with maleic acid as the internal standard (5 mg) for a range of concentrations from 0.033 to 69.18 mg/mL with a resulting correlation coefficient of >0.9999 for all 6 methamphetamine peak groups. The spectra of complex illicit heroin, methamphetamine, MDMA, and cocaine samples are presented, as well as an extensive list of compounds, their solubilities and the solvent(s) and internal standard used. In the experiment, the researchers used many compounds, for example, 2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol dihydrochloride (cas: 2192-20-3Reference of 2192-20-3).

2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol dihydrochloride (cas: 2192-20-3) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. 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.Reference of 2192-20-3

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