Category: piperazines

FGF2/FGFR1 regulates autophagy in FGFR1- amplified non-small cell lung cancer cells was written by Yuan, Hong;Li, Zi-Ming;Shao, Jiaxiang;Ji, Wen-Xiang;Xia, Weiliang;Lu, Shun. And the article was included in Journal of Experimental & Clinical Cancer Research in 2017.HPLC of Formula: 1035270-39-3 This article mentions the following:

Autophagy is a conserved catabolic process to degrade cellular organelles. The role of autophagy in cancer development is complex. Amplification of fibroblast growth factor receptor 1 (FGFR1) is one of the most frequent targets in lung squamous cell carcinoma (SQCC). Whether fibroblast growth factor 2 (FGF2)/FGFR1 contributes to the regulation of autophagy remains elusive. Autophagic activity was evaluated by immunoblotting for microtubule-associated protein 1 light chain 3 (LC3), formation of GFP-LC3 puncta, and monodansylcadaverine (MDC) staining. The effect of autophagy inhibition on cell survival was assessed by cell viability and apoptosis assays. We elucidated that FGFR1 activation suppressed autophagy. Pharmacol. or genetic inhibition of FGFR1 by AZD4547 or FGFR1 short hairpin RNA (shRNA) induced autophagy in FGFR1-amplified non-small-cell lung cancer (NSCLC) cells, H1581 and H520 cells. Mechanistic study revealed that the induction of autophagy by FGFR1 inhibition was mediated through inhibiting the ERK/MAPK pathway not by AKT pathway, accompanied by upregulation of beclin-1. Furthermore, activation of ERK/MAPK by transfection with a constitutively active MEK1 (caMEK1) construct or knockdown of beclin-1 by RNAi could attenuate autophagy induced by FGFR1 inhibition. Beclin-1 expression was inversely correlated with MEK1 phosphorylation. Inhibition of autophagy by beclin-1 silencing could enhance apoptosis after AZD4547 treatment in H1581 and H520 cells. High levels of LC3B mRNA was a marker of poor prognosis in NSCLC patients. Simultaneously inhibiting FGFR1 and autophagy could enhance cell death which should be further explored in vivo. 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: 1035270-39-3HPLC of Formula: 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 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).HPLC of Formula: 1035270-39-3

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

Adult male patient with severe intellectual disability caused by a homozygous mutation in the HNMT gene. was written by Verhoeven, Willem M A;Egger, Jos I M;Janssen, Paddy K C;van Haeringen, Arie. And the article was included in BMJ case reports in 2020.Product Details of 68-88-2 This article mentions the following:

Histamine is involved in various physiological functions like sleep-wake cycle and stress regulation. The histamine N-methyltransferase (HNMT) enzyme is the only pathway for termination of histamine neurotransmission in the central nervous system. Experiments with HNMT knockout mice generated aggressive behaviours and dysregulation of sleep-wake cycles. Recently, seven members of two unrelated consanguineous families have been reported in whom two different missense HNMT mutations were identified. All showed severe intellectual disability, delayed speech development and mild regression from the age of 5 years without, however, any dysmorphisms or congenital abnormality. A diagnosis of mental retardation, autosomal recessive 51 was made. Here, we describe a severely mentally retarded adolescent male born from second cousins with a homozygous mutation in HNMT. His phenotypic profile comprised aggression, delayed speech, autism, sleep disturbances and gastro-intestinal problems. At early age, regression occurred. Treatment with hydroxyzine combined with a histamine-restricted diet resulted in significant general improvement. In the experiment, the researchers used many compounds, for example, 2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol (cas: 68-88-2Product Details of 68-88-2).

2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol (cas: 68-88-2) 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. 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 68-88-2

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

Uncovering the mechanisms of leech and centipede granules in the treatment of diabetes mellitus-induced erectile dysfunction utilising network pharmacology was written by Ma, Jian Xiong;Wang, Bin;Li, Hai Song;Yu, Jia;Hu, Hui Min;Ding, Cai Fei;Chen, Wang Qiang. And the article was included in Journal of Ethnopharmacology in 2021.Quality Control of 2-(2-Ethoxy-5-((4-ethylpiperazin-1-yl)sulfonyl)phenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one This article mentions the following:

Diabetes mellitus-induced erectile dysfunction (DMED) is one of the most common complications of diabetes mellitus. Leech and centipede granules (LCG) have traditionally been used as blood-activating agents in various ethnomedicinal systems of East Asia, especially in China. It is often used to regulate bodily functions and considered as adjuvant therapy for promoting blood circulation, alleviating blood coagulation, activating meridians, and relieving stasis. This study aimed to identify potential genes and mechanisms of LCG on DMED from the network pharmacol. perspective. The active components of LCG were identified by UHPLC-Q-TOF-MS, TCMID, and the BATMAN-TCM databases, and the disease targets of DMED were obtained from the DisGeNET, CooLGeN, GeneCards databases. After identifying DMED targets of LCG, a protein-protein interaction (PPI) network was constructed. Hub genes and significant modules were identified via the MCODE plug-in of Cytoscape software. Then, significant signaling pathways of the modules were identified using the Metascape database. The probable interaction mode of compounds-hub genes is examined using Mol. Operating Environment (MOE) docking software. Besides, we investigated the effects and mechanisms of LCG on improving erectile function in the streptozotocin (STZ)-induced diabetic rats model. Combined UHPLC-Q-TOF-MS anal. with network pharmacol. study, 18 active compounds were selected for target prediction. There are 97 common target genes between LCG and DMED. Enrichment of the KEGG pathway mainly involves in the calcium signaling pathway, NF-kappa B signaling pathway, cGMP-PKG signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, and mTOR signaling pathway. Nine hub genes were regulated by LCG in DMED, including CXCL8, NOS3, CRH, TH, BDNF, DRD4, ACE, CNR1, and HTR1A. The results of mol. docking anal. showed that the tyrosin, ursolic acid, and L-Histidine has a relatively stable interaction with corresponding hub genes via generating hydrogen bonds, H-π, and π-π interactions. Significantly, the results in docking predicted a higher affinity of vardenafil to the hub genes compared to the tyrosin, ursolic acid, and L-Histidine. Furthermore, LCG increased the testosterone, erection frequency, the ratio of ICP and MAP, SOD, cGMP, cAMP as well as decreased the MDA, and AGEs expression levels. And, LCG ameliorated the histol. change of penile tissues in DMED rats. Hence, LCG attenuates oxidative stress, increases NO production; For the mechanism exploration, LCG could significantly upregulate the mRNA and protein expression of CNR1, NOS3, CRH, TH, BDNF, and DRD4, whereas CXCL8, ACE, and HTR1A levels were significantly higher than those in the DMED group. Moreover, LCG activates the NO/cGMP/PKG pathway, PI3K/Akt/nNOS pathway, cAMP/PKA pathway, and inhibits the HIF-1α/mTOR pathway to improve erectile function. Our results suggest that LCG maybe offer a new therapeutic basis for the treatment of DMED via altering the gene expression of involved metabolic pathways. In the experiment, the researchers used many compounds, for example, 2-(2-Ethoxy-5-((4-ethylpiperazin-1-yl)sulfonyl)phenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one (cas: 224785-90-4Quality Control of 2-(2-Ethoxy-5-((4-ethylpiperazin-1-yl)sulfonyl)phenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one).

2-(2-Ethoxy-5-((4-ethylpiperazin-1-yl)sulfonyl)phenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one (cas: 224785-90-4) 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. 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. Quality Control of 2-(2-Ethoxy-5-((4-ethylpiperazin-1-yl)sulfonyl)phenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one

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

Overall survival with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer in the PEARL study was written by Martin, Miguel;Zielinski, Christoph;Ruiz-Borrego, Manuel;Carrasco, Eva;Ciruelos, Eva M.;Munoz, Montserrat;Bermejo, Begona;Margeli, Mireia;Csoszi, Tibor;Anton, Antonio;Turner, Nicholas;Casas, Maria I.;Morales, Serafin;Alba, Emilio;Calvo, Lourdes;de la Haba-Rodriguez, Juan;Ramos, Manuel;Murillo, Laura;Santaballa, Ana;Alonso-Romero, Jose L.;Sanchez-Rovira, Pedro;Corsaro, Massimo;Huang, Xin;Thallinger, Christiane;Kahan, Zsuzsanna;Gil-Gil, Miguel. And the article was included in European Journal of Cancer in 2022.Application of 1211441-98-3 This article mentions the following:

An earlier anal. of the PEARL phase III study showed that palbociclib plus endocrine therapy (ET) does not improve progression-free survival (PFS) over capecitabine in aromatase inhibitor-resistant, hormone receptor-pos./human epidermal growth factor receptor 2-neg. metastatic breast cancer (MBC) patients. Here, we report the final overall survival (OS) anal.Postmenopausal patients (N = 601) were randomized 1:1 to capecitabine or palbociclib plus ET (exemestane, Cohort 1; fulvestrant, Cohort 2). OS was analyzed in Cohort 2, the wild-type ESR1 population and the overall population. Addnl., we analyzed subsequent systemic therapies and explored PFS2 (time from randomization to the end of the first subsequent therapy/death).OS was 31.1 mo for palbociclib plus fulvestrant and 32.8 mo for capecitabine (adjusted hazard ratio [aHR] 1.10, 95% confidence interval [CI] 0.81-1.50, P = 0.550). In the wild-type ESR1 population, OS was 37.2 mo for palbociclib plus ET and 34.8 mo for capecitabine (aHR 1.06, 95% CI 0.81-1.37, P = 0.683). In OS analyses, no subgroup showed superiority for palbociclib plus ET over capecitabine. OS in the overall population was 32.6 mo for palbociclib plus ET and 30.9 mo for capecitabine (P = 0.995). Subsequent systemic therapy was given to 79.8% and 82.9% of patients with palbociclib plus ET and capecitabine, resp. Median PFS2 was similar between study arms (Cohort 2, P = 0.941; wild-type ESR1 population, P = 0.827). No new safety findings were observedPalbociclib plus ET did not show a statistically superior OS compared to capecitabine in MBC patients progressing on aromatase inhibitors.NCT02028507 (ClinTrials.gov), 2013-003170-27 (EudraCT). In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Application of 1211441-98-3).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) 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 1211441-98-3

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

Selective inhibitors of fibroblast activation protein (FAP) with a xanthine scaffold was written by Jansen, Koen;De Winter, Hans;Heirbaut, Leen;Cheng, Jonathan D.;Joossens, Jurgen;Lambeir, Anne-Marie;De Meester, Ingrid;Augustyns, Koen;Van der Veken, Pieter. And the article was included in MedChemComm in 2014.Application of 93643-24-4 This article mentions the following:

Fibroblast activation protein (FAP) is a serine protease that is selectively expressed in many diseases involving activated stroma, including cancer, arthritis and hepatic and pulmonary fibrosis. FAP is closely related to dipeptidyl peptidase IV (DPPIV), of which many inhibitors are known and several are marketed as drugs. One of these is the xanthine derivative linagliptin. In a broad literature screen amongst reported DPPIV inhibitors, linagliptin was the only druglike compound identified that possessed significant FAP potency. Hence, this compound served as a starting point for a SAR study that aimed to identify structural determinants that selectively increase FAP-potency of linagliptin analogs. By investigating the influence of the substitution pattern on N1, N7 and C8 of the xanthine scaffold, we managed to decouple DPPIV and FAP potency and identified the first selective xanthine-based FAP inhibitors with low micromolar potency. Furthermore, these compounds are the only known FAP-inhibitors that do not rely on a warhead functionality to obtain potencies in this range. In the experiment, the researchers used many compounds, for example, (S)-1,4-Diazabicyclo[4.3.0]nonane (cas: 93643-24-4Application of 93643-24-4).

(S)-1,4-Diazabicyclo[4.3.0]nonane (cas: 93643-24-4) 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).Application of 93643-24-4

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

American College of Rheumatology White Paper on Antimalarial Cardiac Toxicity was written by Desmarais, Julianna;Rosenbaum, James T.;Costenbader, Karen H.;Ginzler, Ellen M.;Fett, Nicole;Goodman, Susan;O′Dell, James;Pineau, Christian A.;Schmajuk, Gabriela;Werth, Victoria P.;Link, Mark S.;Kovacs, Richard. And the article was included in Arthritis & Rheumatology in 2021.Recommanded Product: 2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol This article mentions the following:

Hydroxychloroquine (HCQ) and chloroquine (CQ) are well-established medications used in treating systemic lupus erythematosus and rheumatoid arthritis, as well as skin conditions such as cutaneous lupus erythematosus. In rare cases, arrhythmias and conduction system abnormalities, as well as cardiomyopathy, have been reported in association with HCQ/CQ use. Recently, however, the corrected QT interval (QTc)-prolonging potential of these medications, and risk of torsade de pointes (TdP) in particular, have been highlighted in the setting of their exptl. use for COVID-19 infection. This report was undertaken to summarize the current understanding of HCQ/CQ cardiac toxicity, describe QTc prolongation and TdP risks, and discuss areas of priority for future research. A working group of experts across rheumatol., cardiol., and dermatol. performed a nonsystematic literature review and offered a consensus-based expert opinion. Current data clearly indicate that HCQ and CQ are invaluable medications in the management of rheumatic and dermatol. diseases, but they are associated with QTc prolongation by directly affecting cardiac repolarization. Prescribing clinicians should be cognizant of this small effect, especially in patients taking addnl. medications that prolong the QTc interval. Long-term use of HCQ/CQ may lead to a cardiomyopathy associated with arrhythmias and heart failure. Risk and benefit assessment should be considered prior to initiation of any medication, and both initial and ongoing risk-benefit assessments are important with regard to prescription of HCQ/CQ. While cardiac toxicity related to HCQ/CQ treatment of rheumatic diseases is rarely reported, it can be fatal. Awareness of the potential adverse cardiac effects of HCQ and CQ can increase the safe use of these medications. There is a clear need for addnl. research to allow better understanding of the cardiovascular risk and safety profile of these therapies used in the management of rheumatic and cutaneous diseases. In the experiment, the researchers used many compounds, for example, 2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol (cas: 68-88-2Recommanded Product: 2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol).

2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol (cas: 68-88-2) 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).Recommanded Product: 2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol

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

A simple method of hiPSCs differentiation into insulin-producing cells is improved with vitamin C and RepSox was written by Horikawa, Ayumi;Mizuno, Keiko;Tsuda, Kyoko;Yamamoto, Takayoshi;Michiue, Tatsuo. And the article was included in PLoS One in 2021.Synthetic Route of C25H22N6 This article mentions the following:

Human induced pluripotent stem cells (hiPSCs) are considered a promising source of pancreatic β-cells for the treatment of diabetes. However, this approach is limited by issues such as low efficiency and high cost. Here, we have developed a new protocol to induce insulin-producing cells. To reduce costs, we decreased the number of reagents and replaced protein reagents with chem. compounds In this method, we increased induction efficiency with ascorbic acid (vitamin C) and an ALK5 inhibitor, RepSox. In 2D culture, the majority of cells were immature β-cells with low glucose-stimulated insulin secretion. Transferring to 3D culture immediately after endocrine progenitor cell differentiation, however, improved glucose-stimulated insulin secretion. This simplified method will contribute to realizing transplantation therapy of β-cells using iPSCs. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Synthetic Route of C25H22N6).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) 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.Synthetic Route of C25H22N6

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

Desirability-Based Methods of Multiobjective Optimization and Ranking for Global QSAR Studies. Filtering Safe and Potent Drug Candidates from Combinatorial Libraries was written by Cruz-Monteagudo, Maykel;Borges, Fernanda;Cordeiro, M. Natalia D. S.;Cagide Fajin, J. Luis;Morell, Carlos;Molina Ruiz, Reinaldo;Canizares-Carmenate, Yudith;Dominguez, Elena Rosa. And the article was included in Journal of Combinatorial Chemistry in 2008.SDS of cas: 112811-57-1 This article mentions the following:

Up to now, very few applications of multiobjective optimization (MOOP) techniques to quant. structure-activity relationship (QSAR) studies have been reported in the literature. However, none of them report the optimization of objectives related directly to the final pharmaceutical profile of a drug. In this paper, a MOOP method based on Derringer’s desirability function that allows conducting global QSAR studies, simultaneously considering the potency, bioavailability, and safety of a set of drug candidates, is introduced. The results of the desirability-based MOOP (the levels of the predictor variables concurrently producing the best possible compromise between the properties determining an optimal drug candidate) are used for the implementation of a ranking method that is also based on the application of desirability functions. This method allows ranking drug candidates with unknown pharmaceutical properties from combinatorial libraries according to the degree of similarity with the previously determined optimal candidate. Application of this method will make it possible to filter the most promising drug candidates of a library (the best-ranked candidates), which should have the best pharmaceutical profile (the best compromise between potency, safety and bioavailability). In addition, a validation method of the ranking process, as well as a quant. measure of the quality of a ranking, the ranking quality index (Ψ), is proposed. The usefulness of the desirability-based methods of MOOP and ranking is demonstrated by its application to a library of 95 fluoroquinolones, reporting their gram-neg. antibacterial activity and mammalian cell cytotoxicity. Finally, the combined use of the desirability-based methods of MOOP and ranking proposed here seems to be a valuable tool for rational drug discovery and development. In the experiment, the researchers used many compounds, for example, 1-Cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (cas: 112811-57-1SDS of cas: 112811-57-1).

1-Cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (cas: 112811-57-1) 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. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.SDS of cas: 112811-57-1

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

Profiling of LINS01 compounds at human dopamine D₂ and D₃ receptors was written by Correa, Michelle F.;Reiner, David;Fernandes, Gustavo A. B.;Varela, Marina T.;Aranha, Cecilia M. S. Q.;Stark, Holger;Fernandes, Joao Paulo S.. And the article was included in Journal of Chemical Sciences (Berlin, Germany) in 2020.Application In Synthesis of 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea This article mentions the following:

Abstract: Histamine and dopamine neuronal pathways display interesting overlapping in the CNS, especially in the limbic areas, making them very attractive to designing drugs with synergistic and/or additive effects. The roles of these systems to treat schizophrenia, drug addiction, Parkinson’s and Alzheimer’s diseases, among others are widely known. The LINS01 compounds were previously reported as histamine H₃ receptor (H₃R) antagonists and some of them are under evaluation in rodent memory models. Considering their pharmacol. potential and similarities to literature dopamine D₂ receptor (D₂R) and dopamine D₃ receptor (D₃R) ligands, this work aimed to evaluate these compounds as ligands these receptors by using [³H]spiperone displacement assays. A set of 11 compounds containing the dihydrobenzofuranyl-piperazine core with substituents at 5-position of dihydrobenzofuran ring and at the piperazine nitrogen was examined With the LINS01 compounds showing moderate binding affinity, new lead structures for optimization with regards to combined H₃R and D₂R/D₃R-ligands are provided. Graphic abstract: Histamine and dopamine neuronal pathways display interesting overlapping in the CNS, and thus LINS01 compounds previously reported as histamine H₃ receptor antagonists were evaluated as dopamine D₂R and D₃R ligands. In the experiment, the researchers used many compounds, for example, 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8Application In Synthesis of 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea).

3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8) 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.Application In Synthesis of 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea

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

Efficacy of donepezil for the treatment of oxaliplatin-induced peripheral neuropathy: DONEPEZOX, a protocol of a proof of concept, randomised, triple-blinded and multicentre trial was written by Kerckhove, Nicolas;Tougeron, David;Lepage, Come;Pezet, Denis;Le Malicot, Karine;Pelkowski, Manon;Pereira, Bruno;Balayssac, David. And the article was included in BMC Cancer in 2022.Formula: C43H58N4O12 This article mentions the following:

The use of oxaliplatin in digestive tract cancers could induce severe peripheral neuropathy (OIPN) decreasing the quality of life of patients and survivors. There is currently, no univocal treatment for these peripheral neuropathies. Donepezil, a reversible inhibitor of cholinesterase, used to treat Alzheimer’s disease and dementia, is reported to have a good safety profile in humans, and preclin. data have provided initial evidence of its effectiveness in diminishing neuropathic symptoms and related comorbidities in OIPN animal models. The DONEPEZOX trial will be a proof-of-concept, randomised, triple-blinded, and multicentre study. It will be the first clin. trial evaluating the efficacy and safety of donepezil for the management of OIPN. Adult cancer survivors with OIPN that report sensory neuropathy according to QLQ-CIPN20 sensory score (equivalence of a grade ≥ 2), at least 6 mo after the end of an oxaliplatin-based chemotherapy will be included. Eighty patients will be randomly assigned to receive either donepezil or placebo over 16 wk of treatment. The primary endpoint will be the rate of responders (neuropathic grade decreases according to the QLQ-CIPN20 sensory score) in the donepezil arm. The severity of OIPN will be assessed by the QLQ-CIPN20 sensory scale before and after 16 wk of treatment. The comparison vs. the placebo arm will be a secondary objective. The other secondary endpoints will be tolerance to donepezil, the severity and features of OIPN in each arm before and after treatment, related-comorbidities and quality of life. Fleming’s one-stage design will be used for sample size estimation This design yields a type I error rate of 0.0417 and power of 91% for a responder rate of at least 30% in donepezil arm. A total of 80 randomized patients is planned. This study will allow, in the case of pos. results, to initiate a phase 3 randomized and placebo-controlled (primary endpoint) clin. study to assess the therapeutic interest of donepezil to treat OIPN. In the experiment, the researchers used many compounds, for example, 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1Formula: C43H58N4O12).

8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1) 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.Formula: C43H58N4O12

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