Category: piperazines

A theoretical entropy score as a single value to express inhibitor selectivity was written by Uitdehaag, Joost C. M.;Zaman, Guido J. R.. And the article was included in BMC Bioinformatics in 2011.Related Products of 692737-80-7 This article mentions the following:

Designing maximally selective ligands that act on individual targets is the dominant paradigm in drug discovery. Poor selectivity can underlie toxicity and side effects in the clinic, and for this reason compound selectivity is increasingly monitored from very early on in the drug discovery process. To make sense of large amounts of profiling data, and to determine when a compound is sufficiently selective, there is a need for a proper quant. measure of selectivity. Here we propose a new theor. entropy score that can be calculated from a set of IC₅₀ data. In contrast to previous measures such as the ‘selectivity score’, Gini score, or partition index, the entropy score is non-arbitary, fully exploits IC₅₀ data, and is not dependent on a reference kinase. In addition, the entropy score gives the most robust values with data from different sources, because it is less sensitive to errors. We apply the new score to kinase and nuclear receptor profiling data, and to high-throughput screening data. In addition, through analyzing profiles of clin. compounds, we show that a more selective inhibitor is not necessarily more drug-like. For quantifying selectivity from panel profiling, a theor. entropy score is the best method. It is valuable for studying the mol. mechanisms of selectivity, and to steer compound progression in drug discovery programs. In the experiment, the researchers used many compounds, for example, 4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7Related Products of 692737-80-7).

4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7) 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.Related Products of 692737-80-7

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

Simultaneous determination of tandospirone and its active metabolite, 1-[2-pyrimidyl]-piperazine in rat plasma by LC-MS/MS and its application to a pharmacokinetic study was written by Hu, Wenya;Jia, Mi;He, Siyan;Xie, Huiru;Jiang, Xuehua;Wang, Ling. And the article was included in Biomedical Chromatography in 2019.Category: piperazines This article mentions the following:

A rapid, sensitive and selective liquid chromatog.-tandem mass spectrometry method for the detection of tandospirone (TDS) and its active metabolite 1-[2-pyrimidyl]-piperazine (1-PP) in Sprague-Dawley rat plasma is described. It was employed in a pharmacokinetic study. These analytes and the internal standards were extracted from plasma using protein precipitation with acetonitrile, then separated on a CAPCELL PAK ADME C₁₈ column using a mobile phase of acetonitrile and 5 mM ammonium formate acidified with formic acid (0.1%, volume/volume) at a total flow rate of 0.4 mL/min. The detection was performed with a tandem mass spectrometer equipped with an electrospray ionization source. The method was validated to quantify the concentration ranges of 1.000-500.0 ng/mL for TDS and 10.00-500.0 ng/mL for 1-PP. Total time for each chromatograph was 3.0 min. The intra-day precision was between 1.42 and 6.69% and the accuracy ranged from 95.74 to 110.18% for all analytes. Inter-day precision and accuracy ranged from 2.47 to 6.02% and from 98.37 to 105.62%, resp. The lower limits of quantification were 1.000 ng/mL for TDS and 10.00 ng/mL for 1-PP. This method provided a fast, sensitive and selective anal. tool for quantification of tandospirone and its metabolite 1-PP in plasma necessary for the pharmacokinetic investigation. 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: 112457-95-1Category: piperazines).

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. 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

Hemiplegic migraine type 2 with new mutation of the ATP1A2 gene in Japanese cases was written by Oda, Ituki;Danno, Daisuke;Saigoh, Kazumasa;Wolf, Johanna;Kawashita, Norihito;Hirano, Makito;Samukawa, Makoto;Kitamura, Shigekazu;Kikui, Shoji;Takeshima, Takao;Mitsui, Yoshiyuki;Kusunoki, Susumu;Nagai, Yoshitaka. And the article was included in Neuroscience Research (Shannon, Ireland) in 2022.Electric Literature of C27H32Cl2F2N2O3 This article mentions the following:

We analyzed the clin. symptoms of hemiplegic migraine (HM) and their relevance in four Japanese patients considered to have ATP1A2 mutations as a cause. Sequencing of ATP1A2 was performed using the Sanger method in 43 blood samples from clin. suspected patients with familial HM. Subsequently, algorithm anal., allele frequency determination, and three-dimensional structure anal. of the recognized variants were performed, and the recognized variants were evaluated. We found four heterozygous missense mutations in ATP1A2 (Case 1: p.R51C; Case 2: p.R65L; Case 3: p.A269P; Case 4: p.D999H), three of which had not been reported to date. These four mutations may also affect the structure of the protein products, as assessed using a three-dimensional structural anal. In all four cases, the clin. symptoms included visual, sensory, motor, and verbal symptoms and the frequency and duration of headache attacks varied. Addnl., oral administration of a combination of lomerizine hydrochloride and topiramate had a partial effect in three cases. We report four missense mutations in ATP1A2. This report will be useful for the future anal. of mutations and clin. types in Asians, as well as Westerners, with migraine. In the experiment, the researchers used many compounds, for example, 1-(Bis(4-fluorophenyl)methyl)-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride (cas: 101477-54-7Electric Literature of C27H32Cl2F2N2O3).

1-(Bis(4-fluorophenyl)methyl)-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride (cas: 101477-54-7) 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.Electric Literature of C27H32Cl2F2N2O3

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

Evaluation of cariprazine in the treatment of bipolar I and II depression: a randomized, double-blind, placebo-controlled, phase 2 trial. was written by Yatham, Lakshmi N;Vieta, Eduard;Earley, Willie. And the article was included in International clinical psychopharmacology in 2020.Formula: C21H32Cl2N4O This article mentions the following:

This double-blind placebo-controlled, fixed/flexible-dose phase 2 trial assessed the efficacy, safety, and tolerability of cariprazine vs. placebo for depressive episodes associated with bipolar I or II disorder. Primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores (baseline to week 8), and secondary endpoint was mean Clinical Global Impressions-Improvement score (week 8). Patients were randomized (N = 233) 1:1:1 to placebo, ‘low-dose’ 0.25-0.5 mg/day or ‘high-dose’ 1.5-3.0 mg/day cariprazine. Adverse events, laboratory results, vital signs, extrapyramidal symptoms, and suicide risk were monitored. Neither cariprazine group significantly separated from placebo in primary (mixed-effect model repeated measures MADRS least-squares mean differences: low-dose = -0.7, P = 0.7408; high-dose = 0.0, P = 0.9961) or secondary efficacy measures. No new safety signals with cariprazine were observed and common treatment-emergent adverse events (≥5% of cariprazine patients and twice the rate of placebo) included insomnia, akathisia, dry mouth, nausea, weight increased, diarrhea, restlessness, vomiting, musculoskeletal stiffness, migraine, and cough. Metabolic and weight changes were generally similar for cariprazine and placebo. Factors that may have affected the outcome of the trial were identified, which helped to inform the design and conduct of subsequent phase 2b/3 clinical trials of cariprazine in bipolar depression. 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: 839712-12-8Formula: C21H32Cl2N4O).

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 causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. 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).Formula: C21H32Cl2N4O

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

Discovery of Potent and Orally Effective Dual Janus Kinase 2/FLT3 Inhibitors for the Treatment of Acute Myelogenous Leukemia and Myeloproliferative Neoplasms was written by Yang, Tao;Hu, Mengshi;Qi, Wenyan;Yang, Zhuang;Tang, Minghai;He, Jun;Chen, Yong;Bai, Peng;Yuan, Xue;Zhang, Chufeng;Liu, Kongjun;Lu, Yulin;Xiang, Mingli;Chen, Lijuan. And the article was included in Journal of Medicinal Chemistry in 2019.Safety of tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate This article mentions the following:

Herein, the design, synthesis, and structure-activity relationships of a series of unique 4-(1H-pyrazol-4-yl)-pyrimidin-2-amine derivatives that selectively inhibit Janus kinase 2 (JAK2) and FLT3 kinases is described. These screening cascades revealed that I was a preferred compound with IC₅₀ values of 0.7 and 4 nM for JAK2 and FLT3, resp. Moreover, I was a potent JAK2 inhibitor with 37-fold and 56-fold selectivity over JAK1 and JAK3, resp., and possessed an excellent selectivity profile over the other 100 representative kinases. In a series of cytokine-stimulated cell-based assays, I exhibited a higher JAK2 selectivity over other JAK isoforms. The oral administration of 60 mg/kg of I could significantly inhibit tumor growth, with a tumor growth inhibition rate of 93 and 85% in MV4-11 and SET-2 xenograft models, resp. Addnl., I showed an excellent bioavailability (F = 58%), a suitable half-life time (T_1/2 = 4.1 h), a satisfactory metabolic stability, and a weak CYP3A4 inhibitory activity, suggesting that I might be a potential drug candidate for JAK2-driven myeloproliferative neoplasms and FLT3-internal tandem duplication-driven acute myelogenous leukemia. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate (cas: 154590-34-8Safety of tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate).

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

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

Continuation rate for asenapine and brexpiprazole treatment in patients with schizophrenia was written by Inoue, Yuichi;Suzuki, Hidenobu;Hibino, Hiroyuki;Takaya, Atsuhiko;Mikami, Katsunaka;Yamamoto, Kenji;Matsumoto, Hideo. And the article was included in Brain and Behavior in 2021.Reference of 913611-97-9 This article mentions the following:

Introduction : The current study sought to compare the treatment continuation rates of asenapine and brexpiprazole while specifically investigating the factors influencing this index and the clin. efficacy of brexpiprazole. Methods : Retrospective study on patients with schizophrenia who were prescribed either asenapine (n = 73) or brexpiprazole (n = 136), as part of their routine medical care. Results : The treatment continuation rates for asenapine and brexpiprazole were 19.0% and 38.6% at 52 wk, with that of brexpiprazole found to be significantly higher than that of asenapine (p = .002). Moreover, age was found to be a significant factor affecting the treatment continuation rate for brexpiprazole (p = .03). Addnl., patients with a longer continuation duration had significantly lower Clin. Global Impression-Severity of Illness (CGI-S) scale scores compared to those who discontinued early (p = .04). The continuation rate was also significantly higher for those who began using the drug as outpatients compared to those first administered the drug as inpatients (p = .04). Furthermore, disease duration, CGI-S scale, and continuation duration significantly affected the clin. efficacy of brexipiprazole (p < .05 for all). Conclusions : The continuation rate for brexpiprazole increases as the age of the patient increases, as disease severity decreases, and if the patient first uses the drug as an outpatient. Shorter disease duration and longer drug administration may lead to improved clin. efficacy. These results suggest that brexpiprazole is an effective treatment option for maintenance therapy of schizophrenia. 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: 913611-97-9Reference 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. 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. Reference of 913611-97-9

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

Inhibition of S6K1 enhances dichloroacetate-induced cell death was written by Hong, Sung-Eun;Shin, Keong-Sub;Lee, Yun-Han;Seo, Sung-Kum;Yun, Sun-Mi;Choe, Tae-Boo;Kim, Hyun-Ah;Kim, Eun-Kyu;Noh, Woo Chul;Kim, Jong-Il;Hwang, Chang-Sun;Lee, Jin Kyung;Hwang, Sang-Gu;Jin, Hyeon-Ok;Park, In-Chul. And the article was included in Journal of Cancer Research and Clinical Oncology in 2015.Recommanded Product: 1255517-76-0 This article mentions the following:

Purpose: The unique metabolic profile of cancer (aerobic glycolysis) is an attractive therapeutic target for cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, has been shown to reverse glycolytic phenotype and induce mitochondrion-dependent apoptosis. In the present study, we investigated the effects of S6 kinase 1 (S6K1) inhibition on DCA-induced cell death and the underlying mechanisms in breast cancer cells. Methods: Cell death was evaluated by annexin V and PI staining. The synergistic effects of DCA and PF4708671 were assessed by isobologram anal. Small interfering RNA (siRNA) was used for suppressing gene expression. The mRNA and protein levels were measured by RT-PCR and Western blot anal., resp. Results: PF4708671, a selective inhibitor of S6K1, and knockdown of S6K1 with specific siRNA enhanced DCA-induced cell death. Interestingly, a combination of DCA/PF4708671 markedly reduced protein expression of a glycolytic enzyme, hexokinase 2 (HK2). Suppression of HK2 activity using specific siRNA and 2-deoxyglucose (2-DG) further enhanced cell sensitivity to DCA/PF4708671. Overexpression of Myc-tagged HK2 rescued cell death induced by DCA/PF4708671. Conclusions: Based on these findings, we propose that inhibition of S6K1, in combination with the glycolytic inhibitor, DCA, provides effective cancer therapy. In the experiment, the researchers used many compounds, for example, 2-((4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl)methyl)-6-(trifluoromethyl)-1H-benzo[d]imidazole (cas: 1255517-76-0Recommanded Product: 1255517-76-0).

2-((4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl)methyl)-6-(trifluoromethyl)-1H-benzo[d]imidazole (cas: 1255517-76-0) 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. 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.Recommanded Product: 1255517-76-0

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

Highly Efficient Synthesis of 2-Substituted Benzo[ b ]furan Derivatives from the Cross-Coupling Reactions of 2-Halobenzo[ b ]furans with Organoalane Reagents was written by Wen, Chang;Wu, Chuan;Luo, Ruiqiang;Li, Qinghan;Chen, Feng. And the article was included in Synthesis in 2021.SDS of cas: 27469-60-9 This article mentions the following:

A highly efficient and simple route for the synthesis of benzo[ b]furans was developed by palladium-catalyzed cross-coupling reaction of 2-halobenzo[ b]furans with aryl, alkynyl, and alkylaluminum reagents. Various 2-aryl-, 2-alkynyl-, and 2-alkyl benzo[ b]furans was obtained in 23-97% isolated yields using 2-3 mol% PdCl 2/4-6 mol% XantPhos as the catalyst under mild reaction conditions. The aryls beared electron-donating or electron-withdrawing groups in 2-halobenzo[ b]furans gave products in 40-97% isolated yields. In addition, aluminum reagents containing thienyl, furanyl, trimethylsilanyl, and benzyl groups worked efficiently with 2-halobenzo[ b]furans as well, and three bioactive mols. with benzo[ b]furans skeleton were synthesized. Furthermore, the broad substrates scope and the typical maintenance of vigorous efficiency on gram scale made this protocol a potentially practical method to synthesize benzo[ b]furans. On the basis of the exptl. results, a possible catalytic cycle was proposed. In the experiment, the researchers used many compounds, for example, 4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9SDS of cas: 27469-60-9).

4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9) 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).SDS of cas: 27469-60-9

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

Preparation of 1-(5-nitroindolyl-2-carbonyl)-4-[3-(1-methylethylamino)-2-pyridinyl] piperazine was written by Sun, Wenjie;Xiao, Xuhua;Ma, Weiyong. And the article was included in Zhongguo Yiyao Gongye Zazhi in 2011.Formula: C9H12N4O2 This article mentions the following:

5-Nitroindolyl-2-carboxylic acid was converted to the acyl chloride, then the latter was condensed with 1-[3-(1-methylethylamino)-2-pyridinyl]piperazine to prepare 1-(5-nitroindolyl-2-carbonyl)-4-[3-(1-methylethylamino)-2-pyridinyl] piperazine I with an overall yield of about 56%. In the experiment, the researchers used many compounds, for example, 1-(3-Nitropyridin-2-yl)piperazine (cas: 87394-48-7Formula: C9H12N4O2).

1-(3-Nitropyridin-2-yl)piperazine (cas: 87394-48-7) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. 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).Formula: C9H12N4O2

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

General cleavage of nitrogen-nitrogen and nitrogen-oxygen bonds using nickel/aluminum alloy was written by Lunn, George;Sansone, Eric B.;Keefer, Larry K.. And the article was included in Synthesis in 1985.Recommanded Product: Piperazine Dihydrochloride This article mentions the following:

Addition of Ni-Al alloy to KOH solutions of compounds containing N-N or N-O bonds is a general and convenient means for reducing such compounds to the corresponding amines. The method was successfully applied to the reduction of nitrosamines, hydrazines, hydroxylamines, hydroxylamine ethers, triazenes, nitramines, N-oxides, tetrazenes, and nitroso, azo, and azoxy compounds In the experiment, the researchers used many compounds, for example, Piperazine Dihydrochloride (cas: 142-64-3Recommanded Product: Piperazine Dihydrochloride).

Piperazine Dihydrochloride (cas: 142-64-3) 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. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Recommanded Product: Piperazine Dihydrochloride

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