Category: piperazines

Molecular iodine-catalyzed facile procedure for N-Boc protection of amines was written by Varala, Ravi;Nuvula, Sreelatha;Adapa, Srinivas R.. And the article was included in Journal of Organic Chemistry in 2006.Application of 780705-64-8 This article mentions the following:

An efficient and practical protocol for the protection of various structurally and electronically divergent aryl and aliphatic amines using (Boc)₂O in the presence of a catalytic amount of mol. iodine under solvent-free conditions at ambient temperature is presented. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8Application of 780705-64-8).

tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8) 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. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Application of 780705-64-8

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

An improved synthesis of the 5-HT1A receptor agonist Eptapirone free base was written by Peng, Wei;Chen, Jian;Liu, Hui;Li, Xiufang;Deng, Zhiwei;Yuan, Jing;Peng, Yizhou;Yang, Yanjing;Zhong, Shian. And the article was included in Chemical Papers in 2019.HPLC of Formula: 780705-64-8 This article mentions the following:

A method to retro-synthesize eptapirone free base. The compound consists of heterocyclic aromatic portion and aliphatic portion, and the synthetic route consisted of a total of nine steps with an overall yield of 8.8% starting from the com. available materials. The key steps in the synthetic method involved: (1) using sodium hydroxide and ethylene glycol as solvent resulted in a better cyclization and yield (61.6%) of 1,2,4-triazine-3,5(2H,4H)-dione; (2) an acceptable yield (63.1%) of 4-tert-butyl(pyrimidin-2-yl)piperazine-1-carboxylate was obtained under an optimized conditions of using triethylamine as a base, ethanol as a solvent, and a reaction temperature of 50 °C for 16 h with non-metal catalysis and less byproducts; (3) the reaction step of eptapirone could get a better yield (49.6%) with an optimized condition of potassium carbonate as a base, acetonitrile as a solvent, NaI as a catalyst, and a reaction temperature of 50 °C for 12 h by nucleophilic substitution reaction. The main advantages of this route were an acceptable product purity, the com. availability of all starting materials and the absence of high temperature, high pressure and noble metal catalysts, which could result in more feasible com. applications. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8HPLC of Formula: 780705-64-8).

tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.HPLC of Formula: 780705-64-8

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

Synthesis and evaluation of thiopyrano[3,4-c]quinoline-9-carboxamide derivatives as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) was written by Park, Chun-Ho;Chun, Kwangwoo;Joe, Bo-Young;Choi, Jong-Hee;Lee, Han-Chang;Ku, Il-Whea;Kim, Hyun Young;Koh, Seong-Ho;Cho, Goang Won;Kim, Seung Hyun;Kim, Myung-Hwa. And the article was included in Medicinal Chemistry Research in 2012.Product Details of 21867-64-1 This article mentions the following:

A series of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors, 5-oxo-2,4,5,6-tetrahydro-1H-thiopyrano[3,4-c]quinoline-9-carboxamides, were successfully synthesized, and their PARP-1 inhibitory activity was evaluated. These compounds were prepared from the corresponding carboxylate and appropriate amines, and a number of the synthesized compounds were found to have significant PARP-1 activity. Among them, one compound showed potent activity in a PARP-1 enzymic and cell-based assay (IC₅₀ = 0.045 μM, ED₅₀ = 0.54 μM). Mol. modeling confirmed the obtained biol. results. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Product Details of 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) 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. 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.Product Details of 21867-64-1

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

Development of Gleevec Analogues for Reducing Production of β-Amyloid Peptides through Shifting β-Cleavage of Amyloid Precursor Proteins was written by Sun, Weilin;Netzer, William J.;Sinha, Anjana;Gindinova, Katherina;Chang, Emily;Sinha, Subhash C.. And the article was included in Journal of Medicinal Chemistry in 2019.SDS of cas: 162046-66-4 This article mentions the following:

Imatinib mesylate, I, inhibits production of β-amyloid (Aβ) peptides both in cells and in animal models. It reduces both the β-secretase and γ-secretase cleavages of the amyloid precursor protein (APP) and mediates a synergistic effect, when combined with a β-secretase inhibitor, BACE IV. Toward developing more potent brain-permeable leads, we have synthesized and evaluated over 75 I-analogs. Several compounds inhibited production of Aβ peptides with improved activity in cells. These compounds affected β-secretase cleavage of APP similarly to I. Compound II significantly reduced production of the Aβ42 peptide, when administered (100 mg/kg, twice daily by oral gavage) to 5 mo old female mice for 5 days. A combination of compound II with BACE IV also reduced Aβ levels in cells, more than the additive effect of the two compounds These results open a new avenue for developing treatments for Alzheimer’s disease using I-analogs. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4SDS of cas: 162046-66-4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) 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 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: 162046-66-4

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

Discovery of the selective and efficacious inhibitors of FLT3 mutations was written by Zhi, Yanle;Li, Baoquan;Yao, Chao;Li, Hongmei;Chen, Puzhou;Bao, Jiyin;Qin, Tianren;Wang, Yue;Lu, Tao;Lu, Shuai. And the article was included in European Journal of Medicinal Chemistry in 2018.Reference of 182618-86-6 This article mentions the following:

Fms-like tyrosine kinase 3 (FLT3) is among the most frequently mutated protein in acute myeloid leukemia (AML), which has been confirmed as an important drug target for AML chemotherapy. Starting from the lead compound LT-106-175, a series of 1-H-pyrazole-3-carboxamide derivatives were synthesized to improve the FLT3 inhibitory potency and selectivity. Among them, compound 50 (4-((2-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)-N-(4-(piperazin-1-yl)phenyl)-1H-pyrazole-3-carboxamide) was identified as a highly potent and selective FLT3 inhibitor (IC₅₀ = 0.213 nM), which showed equal activities against various mutants of FLT3 including FLT3 (ITD)-D835V and FLT3 (ITD)-F691L that is resistant to quizartinib. Compound 50 also exhibited efficacy against the human AML cell line MV4-11 (IC₅₀ = 16.1 nM) harboring FLT3-ITD mutants. Inversely, compound 50 displayed no cytotoxicity to FLT3-independent cells, and the biochem. analyses showed that its effects were related to the inhibition of FLT3 signal pathways. Addnl., compound 50 induced apoptosis in MV4-11 cell as demonstrated by flow cytometry. Moreover, compound 50 showed enhanced metabolic stability. Altogether, it was concluded that compound 50 could be a promising FLT3 inhibitor for further developing therapeutic remedy of AML. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6Reference of 182618-86-6).

1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. 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 182618-86-6

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

Synthesis, characterization, and biological activity of novel metronidazole-piperazine amides was written by Al-Qtaitat, Malath A.;Saadeh, Haythem A.;Al-Bakri, Amal G.;Kaur, Hargobinder;Goyal, Kapil;Sehgal, Rakesh;Mubarak, Mohammad S.. And the article was included in Monatshefte fuer Chemie in 2015.Safety of 1-Propylpiperazine This article mentions the following:

A new series of metronidazole derivatives containing piperazine rings were prepared via the reaction of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)acetyl chloride with selected substituted piperazines in the presence of a base. Structures of the new compounds were confirmed by NMR and MS spectral data and by elemental analyses. The antibacterial and anti-parasitic activities of these compounds were evaluated in vitro. Some of the newly synthesized compounds exhibited superior activity against Clostridium sporogenes bacteria compared to the standard drug metronidazole (I). On the other hand, other derivatives exhibited remarkable antigiardial activity and were found to be more active than metronidazole with IC₅₀ ranging from 1.8 to 6.7 μg/dm³. 1-Ethyl-4-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]piperazine (II) also exhibited antigiardial activity with similar IC₅₀ value (7.6 μg/cm³) as compared to the reference drug metronidazole (IC₅₀ = 7.4 μg/cm³). Similarly, several of the new compounds exhibited significant antitrichomonal activity and found to be more active than metronidazole with IC₅₀ ranging from 6.7 to 8.65 μg/cm³ as compared to the reference drug metronidazole (8.9 μg/cm³). In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Safety of 1-Propylpiperazine).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. 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 1-Propylpiperazine

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

Structural Mechanisms Determining Inhibition of the Collagen Receptor DDR1 by Selective and Multi-Targeted Type II Kinase Inhibitors was written by Canning, Peter;Tan, Li;Chu, Kiki;Lee, Sam W.;Gray, Nathanael S.;Bullock, Alex N.. And the article was included in Journal of Molecular Biology in 2014.Computed Properties of C14H20F3N3 This article mentions the following:

The discoidin domain receptors (DDRs), DDR1 and DDR2, form a unique subfamily of receptor tyrosine kinases that are activated by the binding of triple-helical collagen. Excessive signaling by DDR1 and DDR2 has been linked to the progression of various human diseases, including fibrosis, atherosclerosis and cancer. The authors report the inhibition of these unusual receptor tyrosine kinases by the multi-targeted cancer drugs imatinib and ponatinib, as well as the selective type II inhibitor DDR1-IN-1. Ponatinib is identified as the more potent mol., which inhibits DDR1 and DDR2 with an IC₅₀ of 9 nM. Co-crystal structures of human DDR1 reveal a DFG-out conformation (DFG, Asp-Phe-Gly) of the kinase domain that is stabilized by an unusual salt bridge between the activation loop and αD helix. Differences to Abelson kinase (ABL) are observed in the DDR1 P-loop, where a β-hairpin replaces the cage-like structure of ABL. P-loop residues in DDR1 that confer drug resistance in ABL are therefore accommodated outside the ATP pocket. Whereas imatinib and ponatinib bind potently to both the DDR and ABL kinases, the hydrophobic interactions of the ABL P-loop appear poorly satisfied by DDR1-IN-1 suggesting a structural basis for its DDR1 selectivity. Such inhibitors may have applications in clin. indications of DDR1 and DDR2 overexpression or mutation, including lung cancer. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Computed Properties of C14H20F3N3).

4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) 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.Computed Properties of C14H20F3N3

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

Structure-Activity Relationship Studies of Mitogen Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 and BCR-ABL1 Inhibitors Targeting Chronic Myeloid Leukemic Cells was written by Cherian, Joseph;Nacro, Kassoum;Poh, Zhi Ying;Guo, Samantha;Jeyaraj, Duraiswamy A.;Wong, Yun Xuan;Ho, Melvyn;Yang, Hai Yan;Joy, Joma Kanikadu;Kwek, Zekui Perlyn;Liu, Boping;Wee, John Liang Kuan;Ong, Esther HQ;Choong, Meng Ling;Poulsen, Anders;Lee, May Ann;Pendharkar, Vishal;Ding, Li Jun;Manoharan, Vithya;Chew, Yun Shan;Sangthongpitag, Kanda;Lim, Sharon;Ong, S. Tiong;Hill, Jeffrey;Keller, Thomas H.. And the article was included in Journal of Medicinal Chemistry in 2016.Name: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline This article mentions the following:

Clin. used BCR-ABL1 inhibitors for the treatment of chronic myeloid leukemia do not eliminate leukemic stem cells (LSC). It has been shown that MNK1 and 2 inhibitors prevent phosphorylation of eIF4E and eliminate the self-renewal capacity of LSCs. Herein, the authors describe the identification of novel dual MNK1 and 2 and BCR-ABL1 inhibitors, starting from the known kinase inhibitor. Initial structure-activity relationship studies resulted in a compound with loss of BCR-ABL1 inhibition. Further modification led to orally bioavailable dual MNK1 and 2 and BCR-ABL1 inhibitors I and II, which are efficacious in a mouse xenograft model and also reduce the level of phosphorylated eukaryotic translation initiation factor 4E in the tumor tissues. Kinase selectivity of these compounds is also presented. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Name: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline).

4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. 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.Name: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline

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

Discovery of 2-(1H-imidazo-2-yl)piperazines as a new class of potent and non-cytotoxic inhibitors of Trypanosoma brucei growth in vitro was written by Ferrigno, Federica;Biancofiore, Ilaria;Malancona, Savina;Ponzi, Simona;Paonessa, Giacomo;Graziani, Rita;Bresciani, Alberto;Gennari, Nadia;Di Marco, Annalise;Kaiser, Marcel;Summa, Vincenzo;Harper, Steven;Ontoria, Jesus M.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2018.Formula: C18H24N2O6 This article mentions the following:

The identification of a new series of growth inhibitors of Trypanosoma brucei rhodesiense, causative agent of Human African Trypanosomiasis (HAT), is described. A selection of compounds from our inhouse compound collection was screened in vitro against the parasite leading to the identification of compounds with nanomolar inhibition of T. brucei growth. Preliminary SAR on the hit compound led to the identification of compound 34 that shows low nanomolar parasite growth inhibition (T. brucei EC₅₀ 5 nM), is not cytotoxic (HeLa CC₅₀ > 25,000 nM) and is selective over other parasites, such as Trypanosoma cruzi and Plasmodium falciparum (T. cruzi EC₅₀ 8120 nM, P. falciparum EC₅₀ 3624 nM). In the experiment, the researchers used many compounds, for example, 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (cas: 149057-19-2Formula: C18H24N2O6).

4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (cas: 149057-19-2) 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. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Formula: C18H24N2O6

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

A Putative Single-Photon Emission CT Imaging Tracer for Erythropoietin-Producing Hepatocellular A2 Receptor was written by Furukawa, Takenori;Kimura, Hiroyuki;Torimoto, Hanae;Yagi, Yusuke;Kawashima, Hidekazu;Arimitsu, Kenji;Yasui, Hiroyuki. And the article was included in ACS Medicinal Chemistry Letters in 2021.COA of Formula: C14H20F3N3 This article mentions the following:

Erythropoietin-producing hepatocellular (Eph) receptors are receptor tyrosine kinases involved in cell-cell contact. The EphA2 receptor is associated with cancer proliferation and migration. Therefore, EphA2 receptor imaging has the potential for cancer diagnosis. Here, we synthesized N-(5-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)-2-methylphenyl)-5-[¹²³I]iodonicotinamide ([¹²³I]ETB) and evaluated it as an imaging tracer for single-photon emission computed tomog. (SPECT) imaging of the EphA2 receptor. [¹²³I]ETB was designed on the basis of ALW-II-41-27, an inhibitor of EphA2 receptor kinase. Nonradioactive ETB was also synthesized and has been shown to efficiently inhibit EphA2 receptor kinase activity in vitro (IC₅₀: ETB, 90.2 ± 18.9 nM). A cell-binding assay demonstrated that [¹²⁵I]ETB binds specifically to the EphA2 receptor. The ex vivo biodistribution study of [¹²⁵I]ETB in U87MG tumor-bearing mice also revealed tumor uptake (2.2% ID/g at 240 min). In addition, [¹²³I]ETB uptake in tumors was visualized via SPECT/CT imaging. On the basis of the above, [¹²³I]ETB can be considered a potential SPECT imaging tracer for the EphA2 receptor. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6COA of Formula: C14H20F3N3).

4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) 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. COA of Formula: C14H20F3N3

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