February 2023 | Page 55 of 69 | Heterocyclic Building Blocks-piperazine

Hu, Shuping et al. published their research in Journal of Chromatography A in 2021 | CAS: 113617-63-3

1-Cyclopropyl-7-(cis-3,5-dimethylpiperazin-1-yl)-5,6,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (cas: 113617-63-3) 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. 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.Product Details of 113617-63-3

Development of a pH-dependent homogeneous liquid-liquid extraction by cold-induced phase separation in acetonitrile/water mixtures for determination of quinolone residues in animal-derived foods was written by Hu, Shuping;Zhao, Min;Wang, Zhongle;Yang, Jiaying;Chen, Dawei;Yan, Pengcheng. And the article was included in Journal of Chromatography A in 2021.Product Details of 113617-63-3 This article mentions the following:

A simple extraction procedure coupled with liquid chromatog.-Q Orbitrap high resolution mass spectrometry (LC-Q Orbitrap HRMS) for the determination of 19 quinolones in animal-derived foods (pork, fish, egg and milk) has been developed. Sample preparation is based on homogeneous liquid-liquid extraction at pH > 9 using water-miscible acetonitrile with cold-induced phase separation The procedure allowed one-step enrichment and cleanup of all the 19 quinolones with different logP properties to lower aqueous phase, which eliminated the process of preconcentration and re-dissolution for sample solution Furthermore, an adsorption phenomenon was observed between conventional borosilicate glass injection vials and most of quinolones. In detection anal., a scheduled variable full scan strategy was performed to improve detection performance in Q Orbitrap HRMS. Under optimal conditions, a superior limit of quantitation (0.028-0.192μg/kg) in animal-derived foods was achieved using this proposed method. Lastly, this method was validated and applied successfully in real samples. In the experiment, the researchers used many compounds, for example, 1-Cyclopropyl-7-(cis-3,5-dimethylpiperazin-1-yl)-5,6,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (cas: 113617-63-3Product Details of 113617-63-3).

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

Koufaki, Maria et al. published their research in Bioorganic & Medicinal Chemistry in 2006 | CAS: 72141-41-4

(4-Nitrophenyl)(piperazin-1-yl)methanone (cas: 72141-41-4) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. 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: C11H13N3O3

Synthesis and biological evaluation of benzopyran analogues bearing class III antiarrhythmic pharmacophores was written by Koufaki, Maria;Kiziridi, Christina;Papazafiri, Panagiota;Vassilopoulos, Athanasios;Varro, Andras;Nagy, Zsolt;Farkas, Attila;Makriyannis, Alexandros. And the article was included in Bioorganic & Medicinal Chemistry in 2006.Formula: C11H13N3O3 This article mentions the following:

We have synthesized a series of compounds combining the hydroxy-benzopyran ring of vitamin E with the methylsulfonylaminophenyl group of class III antiarrhythmic drugs, connected through tertiary amine moieties. Evaluation of the antiarrhythmic and antioxidant activity of the new compounds was carried out on isolated rat heart preparations using the non-recirculating Langendorff mode. The new analogs were present, at 10 μM concentration, during ischemia and reperfusion. Selected compounds were further studied by a conventional microelectrode method in order to get insight into their cellular mode of action. The most active compound, N-[4-[2-[[2-(3,4-dihydro-6-hydroxy-2,2,7,8-tetramethyl-2H-1-benzopyran-5-yl)ethyl] methylamine]ethyl]phenyl]methanesulfonamide (19a, I), reduces premature beats, prolongs QT and QRS intervals during ischemia and reperfusion, and reduces MDA content, leading to a fast recovery of the heart. In addition, it exhibits moderate class III antiarrhythmic action. In the experiment, the researchers used many compounds, for example, (4-Nitrophenyl)(piperazin-1-yl)methanone (cas: 72141-41-4Formula: C11H13N3O3).

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

Caciolla, Jessica et al. published their research in Bioorganic Chemistry in 2021 | CAS: 27469-60-9

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

Multifaceted activity of polycyclic MDR revertant agents in drug-resistant leukemic cells: Role of the spacer was written by Caciolla, Jessica;Picone, Giovanna;Farruggia, Giovanna;Valenti, Dario;Rampa, Angela;Malucelli, Emil;Belluti, Federica;Trezza, Alfonso;Spiga, Ottavia;Iotti, Stefano;Gobbi, Silvia;Cappadone, Concettina;Bisi, Alessandra. And the article was included in Bioorganic Chemistry in 2021.HPLC of Formula: 27469-60-9 This article mentions the following:

A small library of derivatives carrying a polycyclic scaffold recently identified by us as a new privileged structure in medicinal chem. was designed and synthesized, aiming at obtaining potent MDR reverting agents also endowed with antitumor properties. In particular, as a follow-up of our previous studies, attention was focused on the role of the spacer connecting the polycyclic core with a properly selected nitrogen-containing group. A relevant increase in reverting potency was observed, going from the previously employed but-2-ynyl- to a pent-3-ynylamino moiety, as in compounds 3d and 3e, while the introduction of a triazole ring proved to differently impact on the activity of the compounds The docking results supported the data obtained by biol. tests, showing, for the most active compounds, the ability to establish specific bonds with P-glycoprotein. Moreover, a multifaceted anticancer profile and dual in vitro activity was observed for all compounds, showing both revertant and antitumor effects on leukemic cells. In this respect, 3c emerged as a “triple-target” agent, endowed with a relevant reverting potency, a considerable antiproliferative activity and a collateral sensitivity profile. In the experiment, the researchers used many compounds, for example, 4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9HPLC of Formula: 27469-60-9).

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

Shum, Michael et al. published their research in Diabetologia in 2016 | CAS: 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. 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.Safety of 2-((4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl)methyl)-6-(trifluoromethyl)-1H-benzo[d]imidazole

Pharmacological inhibition of S6K1 increases glucose metabolism and Akt signalling in vitro and in diet-induced obese mice was written by Shum, Michael;Bellmann, Kerstin;St-Pierre, Philippe;Marette, Andre. And the article was included in Diabetologia in 2016.Safety of 2-((4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl)methyl)-6-(trifluoromethyl)-1H-benzo[d]imidazole This article mentions the following:

Aims/hypothesis: The mammalian target of rapamycin complex 1 (mTORC1)/p70 ribosomal S6 kinase (S6K)1 pathway is overactivated in obesity, leading to inhibition of phosphoinositide 3-kinase (PI3K)/Akt signalling and insulin resistance. However, chronic mTORC1 inhibition by rapamycin impairs glucose homeostasis because of robust induction of liver gluconeogenesis. Here, we compared the effect of rapamycin with that of the selective S6K1 inhibitor, PF-4708671, on glucose metabolism in vitro and in vivo. Methods: We used L6 myocytes and FAO hepatocytes to explore the effect of PF-4708671 on the regulation of glucose uptake, glucose production and insulin signalling. We also treated high-fat (HF)-fed obese mice for 7 days with PF-4708671 in comparison with rapamycin to assess glucose tolerance, insulin resistance and insulin signalling in vivo. Results: Chronic rapamycin treatment induced insulin resistance and impaired glucose metabolism in hepatic and muscle cells. Conversely, chronic S6K1 inhibition with PF-4708671 reduced glucose production in hepatocytes and enhanced glucose uptake in myocytes. Whereas rapamycin treatment inhibited Akt phosphorylation, PF-4708671 increased Akt phosphorylation in both cell lines. These opposite effects of the mTORC1 and S6K1 inhibitors were also observed in vivo. Indeed, while rapamycin treatment induced glucose intolerance and failed to improve Akt phosphorylation in liver and muscle of HF-fed mice, PF-4708671 treatment improved glucose tolerance and increased Akt phosphorylation in metabolic tissues of these obese mice. Conclusions/interpretation: Chronic S6K1 inhibition by PF-4708671 improves glucose homeostasis in obese mice through enhanced Akt activation in liver and muscle. Our results suggest that specific S6K1 blockade is a valid pharmacol. approach to improve glucose disposal in obese diabetic individuals. 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: 1255517-76-0Safety of 2-((4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl)methyl)-6-(trifluoromethyl)-1H-benzo[d]imidazole).

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

Dayananda, A. S. et al. published their research in Acta Crystallographica, Section E: Structure Reports Online in 2012 | CAS: 27469-60-9

4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9) 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. 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. Electric Literature of C17H18F2N2

1-{4-[Bis(4-fluorophenyl)methyl]piperazin-1-yl}ethanone was written by Dayananda, A. S.;Yathirajan, H. S.;Keeley, Amanda C.;Jasinski, Jerry P.. And the article was included in Acta Crystallographica, Section E: Structure Reports Online in 2012.Electric Literature of C17H18F2N2 This article mentions the following:

In the title compound, C₁₉H₂₀F₂N₂O, the six-membered piperazine group adopts a slightly distorted chair conformation. The dihedral angle between the mean planes of the two benzene rings is 73.4(6)°. The mean plane of the ethanone group is twisted from the mean planes of the two benzene rings by 66.7(8) and 86.2(6)°. In the crystal, C-H···O and C-H···F interactions link the mols., forming a three-dimensional structure. Crystallog. data and at. coordinates are given. In the experiment, the researchers used many compounds, for example, 4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9Electric Literature of C17H18F2N2).

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

Zhao, Bin et al. published their research in ACS Medicinal Chemistry Letters in 2016 | CAS: 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. 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. Computed Properties of C16H22N2O4

Discovery of Substituted 1H-Pyrazolo[3,4-b]pyridine Derivatives as Potent and Selective FGFR Kinase Inhibitors was written by Zhao, Bin;Li, Yixuan;Xu, Pan;Dai, Yang;Luo, Cheng;Sun, Yiming;Ai, Jing;Geng, Meiyu;Duan, Wenhu. And the article was included in ACS Medicinal Chemistry Letters in 2016.Computed Properties of C16H22N2O4 This article mentions the following:

Fibroblast growth factor receptors (FGFRs) are important targets for cancer therapy. Herein, we describe the design, synthesis, and biol. evaluation of a novel series of 1H-pyrazolo[3,4-b]pyridine derivatives as potent and selective FGFR kinase inhibitors. On the basis of its excellent in vitro potency and favorable pharmacokinetic properties, compound I was selected for in vivo evaluation and showed significant antitumor activity in a FGFR1-driven H1581 xenograft model. These results indicated that I would be a promising candidate for further drug development. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Computed Properties of C16H22N2O4).

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

Manetti, Dina et al. published their research in Journal of Medicinal Chemistry in 2000 | CAS: 21867-64-1

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.SDS of cas: 21867-64-1

Molecular Simplification of 1,4-Diazabicyclo[4.3.0]nonan-9-ones Gives Piperazine Derivatives That Maintain High Nootropic Activity was written by Manetti, Dina;Ghelardini, Carla;Bartolini, Alessandro;Dei, Silvia;Galeotti, Nicoletta;Gualtieri, Fulvio;Romanelli, Maria Novella;Teodori, Elisabetta. And the article was included in Journal of Medicinal Chemistry in 2000.SDS of cas: 21867-64-1 This article mentions the following:

Several 4-substituted 1-acylpiperazines, obtained by mol. simplification of 4-substituted 1,4-diazabicyclo[4.3.0]nonan-9-ones, have been synthesized and tested in vivo on the mouse passive avoidance test, to evaluate their nootropic activity. The results show that, apparently, an N-acylpiperazine group can mimic the 2-pyrrolidinone ring of 1,4-diazabicyclo[4.3.0]nonan-9-one, as the compounds of the new series maintain high nootropic activity. Moreover mol. simplification produces more clear-cut structure-activity relationships with respect to the parent series. The mechanism of action also appears to be similar in the two series. In fact, although the mol. mechanism remains to be elucidated, the most potent compound of each class is able to increase acetylcholine release in rat brain. Piperazine derivatives represent a new class of nootropic drugs with an in vivo pharmacol. profile very similar to that of piracetam, showing much higher potency with respect to the reference compound Among the compounds studied, 1-benzoyl-4-propionylpiperazine (DM235) shows outstanding potency, being active at a dose of 0.001 mg kg^-1 s.c. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1SDS of cas: 21867-64-1).

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

Larsen, Matthew A. et al. published their research in Journal of the American Chemical Society in 2014 | CAS: 780705-64-8

tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 闁硅櫣鐓?and boils at 125闂?30 闁硅櫣鐓? 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.SDS of cas: 780705-64-8

Iridium-Catalyzed C-H Borylation of Heteroarenes: Scope, Regioselectivity, Application to Late-Stage Functionalization, and Mechanism was written by Larsen, Matthew A.;Hartwig, John F.. And the article was included in Journal of the American Chemical Society in 2014.SDS of cas: 780705-64-8 This article mentions the following:

A study on the iridium-catalyzed C-H borylation of heteroarenes is reported. Several heteroarenes containing multiple heteroatoms were amenable to C-H borylation catalyzed by the combination of an iridium(I) precursor and tetramethylphenanthroline. The investigations of the scope of the reaction led to the development of powerful rules for predicting the regioselectivity of borylation, foremost of which is that borylation occurs distal to nitrogen atoms. One-pot functionalizations are reported of the heteroaryl boronate esters formed in situ, demonstrating the usefulness of the reported methodol. for the synthesis of complex heteroaryl structures. Application of this methodol. to the synthesis and late-stage functionalization of biol. active compounds is also demonstrated. Mechanistic studies show that basic heteroarenes can bind to the catalyst and alter the resting state from the olefin-bound complex observed during arene borylation to a species containing a bound heteroarene, leading to catalyst deactivation. Studies on the origins of the observed regioselectivity show that borylation occurs distal to N-H bonds due to rapid N-H borylation, creating an unfavorable steric environment for borylation adjacent to these bonds. Computational studies and mechanistic studies show that the lack of observable borylation of C-H bonds adjacent to basic nitrogen is not the result of coordination to a bulky Lewis acid prior to C-H activation, but the combination of a higher-energy pathway for the borylation of these bonds relative to other C-H bonds and the instability of the products formed from borylation adjacent to basic nitrogen. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8SDS of cas: 780705-64-8).

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

Kim, Seong Heon et al. published their research in Bioorganic & Medicinal Chemistry Letters in 2011 | CAS: 207284-20-6

(S)-2-Ethylpiperazine (cas: 207284-20-6) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Recommanded Product: (S)-2-Ethylpiperazine

III. Identification of novel CXCR3 chemokine receptor antagonists with a pyrazinyl-piperazinyl-piperidine scaffold was written by Kim, Seong Heon;Anilkumar, Gopinadhan N.;Zawacki, Lisa Guise;Zeng, Qingbei;Yang, De-Yi;Shao, Yuefei;Dong, Guizhen;Xu, Xiaolian;Yu, Wensheng;Jiang, Yueheng;Jenh, Chung-Her;Hall, James W. III;Carroll, Carolyn DiIanni;Hobbs, Doug W.;Baldwin, John J.;McGuinness, Brian F.;Rosenblum, Stuart B.;Kozlowski, Joseph A.;Shankar, Bandarpalle B.;Shih, Neng-Yang. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2011.Recommanded Product: (S)-2-Ethylpiperazine This article mentions the following:

The SAR of a novel pyrazinyl-piperazinyl-piperidine scaffold with CXCR3 receptor antagonist activity was explored. Optimization of the DMPK profile and reduction of hERG inhibition is described. One compound with single-digit CXCR3 affinity and good rat PK and hERG profiles has been identified as a lead for further study. In the experiment, the researchers used many compounds, for example, (S)-2-Ethylpiperazine (cas: 207284-20-6Recommanded Product: (S)-2-Ethylpiperazine).

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

Hori, Manabu et al. published their research in Chemical & Pharmaceutical Bulletin in 1990 | CAS: 21867-64-1

1-Propylpiperazine (cas: 21867-64-1) 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.Synthetic Route of C7H16N2

Novel 4-substituted 2-piperazinylquinazolines as potent anticonvulsive and antihypoxic agents was written by Hori, Manabu;Iemura, Ryuichi;Hara, Hideaki;Ozaki, Akio;Sukamoto, Takayuki;Ohtaka, Hiroshi. And the article was included in Chemical & Pharmaceutical Bulletin in 1990.Synthetic Route of C7H16N2 This article mentions the following:

Piperazinylquinazolines, e.g. I [R = Me, Ph, CH₂Ph, CH₂CH:CH₂, (CH₂)_nMe, R¹ = Me, CH₂Ph, (CH₂)_nMe, n = 2-4] were prepared and examined for anticonvulsive and antihypoxic activities. The anal. of quant. structure-activity relationships indicated that the anticonvulsive activity was related to the lipophilicity of the compounds Most of the alkoxyquinazolines I showed potent anticonvulsive and antihypoxic activities. There is a good correlation between the potencies of these activities. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Synthetic Route of C7H16N2).

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