Month: February 2023

Synthesis, molecular docking and biological evaluation of metronidazole derivatives containing piperazine skeleton as potential antibacterial agents was written by Wang, She-Feng;Yin, Yong;Qiao, Fang;Wu, Xun;Sha, Shao;Zhang, Li;Zhu, Hai-Liang. And the article was included in Bioorganic & Medicinal Chemistry in 2014.Related Products of 27469-60-9 This article mentions the following:

Metronidazole has a broad-spectrum antibacterial activity. Hereby a series of novel metronidazole derivatives were designed and synthesized based on nitroimidazole scaffold in order to find some more potent antibacterial drugs. For these compounds which were reported for the first time, their antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus were tested. These compounds showed good antibacterial activities against Gram-pos. strains. One compound represented the most potent antibacterial activity against S. aureus ATCC 25923 with MIC of 0.003 渭g/mL and it showed the most potent activity against S. aureus TyrRS with IC₅₀ of 0.0024 渭M. Mol. docking of one compound into S. aureus tyrosyl-tRNA synthetase active site were also performed to determine the probable binding mode. In the experiment, the researchers used many compounds, for example, 4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9Related Products of 27469-60-9).

4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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. Related Products of 27469-60-9

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

Homo-PROTAC mediated suicide of MDM2 to treat non-small cell lung cancer was written by He, Shipeng;Ma, Junhui;Fang, Yuxin;Liu, Ying;Wu, Shanchao;Dong, Guoqiang;Wang, Wei;Sheng, Chunquan. And the article was included in Acta Pharmaceutica Sinica B in 2021.Product Details of 548472-68-0 This article mentions the following:

The dose-related adverse effects of MDM2-P53 inhibitors have caused significant concern in the development of clin. safe anticancer agents. Herein we report an unprecedented homo-PROTAC strategy for more effective disruption of MDM2-P53 interaction. The design concept is inspired by the capacity of sub-stoichiometric catalytic PROTACs enabling to degrade an unwanted protein and the dual functions of MDM2 as an E3 ubiquitin ligase and a binding protein with tumor suppressor P53. The new homo-PROTACs are designed to induce self-degradation of MDM2. The results of the investigation have shown that PROTAC 11a efficiently dimerizes MDM2 with highly competitive binding activity and induces proteasome-dependent self-degradation of MDM2 in A549 non-small cell lung cancer cells. Furthermore, markedly, enantiomer 11a-1 exhibits potent in vivo antitumor activity in A549 xenograft nude mouse model, which is the first example of homo-PROTAC with in vivo therapeutic potency. This study demonstrates the potential of the homo-PROTAC as an alternative chem. tool for tumorigenic MDM2 knockdown, which could be developed into a safe therapy for cancer treatment. In the experiment, the researchers used many compounds, for example, 4-(cis-4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one (cas: 548472-68-0Product Details of 548472-68-0).

4-(cis-4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one (cas: 548472-68-0) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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 548472-68-0

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

Reduction of 2,5-dioxopiperazines with lithium aluminum hydride was written by Langenbeck, Wolfgang;Augustin, Manfred;Boehm, Ralf;Hoffmann, Siegfried. And the article was included in Journal fuer Praktische Chemie (Leipzig) in 1964.Synthetic Route of C4H12Cl2N2 This article mentions the following:

2,5-Di-oxopiperazines added to excess LiAlH₄ in dry tetrahydrofuran, the mixture refluxed 165 hrs., the excess LiAlH₄ decomposed with dilute H₂SO₄, the solution extracted with Et₂O, the raffinate alkalinized with KOH and steam-distilled, the distillate acidified with HCl and evaporated, and the residue crystallized from EtOH or EtOH-Et₂O gave the piperazine hydrochlorides (substituents and % yield given): none, 40; 1,4-dimethyl, 62; 1,4-dibenzyl (free base m. 92掳), 57; 3,6-dimethyl, 55; 3,6-dimethyl, 38; 3,6-diisopropyl, 38; and 3,6-diisobutyl, 48 (250 hrs. reflux). In the experiment, the researchers used many compounds, for example, Piperazine Dihydrochloride (cas: 142-64-3Synthetic Route of C4H12Cl2N2).

Piperazine Dihydrochloride (cas: 142-64-3) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Synthetic Route of C4H12Cl2N2

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

A multi-residue method by supercritical fluid chromatography coupled with tandem mass spectrometry method for the analysis of chiral and non-chiral chemicals of emerging concern in environmental samples was written by Rice, Jack;Lubben, Anneke;Kasprzyk-Hordern, Barbara. And the article was included in Analytical and Bioanalytical Chemistry in 2020.Synthetic Route of C23H32N6O4S This article mentions the following:

Abstract: This manuscript presents the development, validation and application of a multi-residue supercritical fluid chromatog. coupled with tandem mass spectrometry method for the anal. of 140 chiral and non-chiral chems. of emerging concern in environmental samples, with 81 compounds being fully quant., 14 semi-quant. and 45 qual., validated according to European Medicine Agency (EMA) guidelines (European Medicines Agency 2019). One unified LC-MS method was used to analyze all analytes, which were split into three injection methods to ensure sufficient peak resolution The unified method provided an average of 113% accuracy and 4.5% precision across the analyte range. Limits of detection were in the range of 35 pg L^-1-0.7 渭g L^-1, in both river water and wastewater, with an average LOD of 33 ng L^-1. The method was combined with solid-phase extraction and applied in environmental samples, showing very good accuracy and precision, as well as excellent chromatog. resolution of a range of chiral enantiomers including beta-blockers, benzodiazepines and antidepressants. The method resulted in quantification of 75% of analytes in at least two matrixes, and 56% in the trio of environmental matrixes of river water, effluent wastewater and influent wastewater, enabling its use in monitoring compounds of environmental concern, from their sources of origin through to their discharge into the environment. 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: 224785-90-4Synthetic Route of C23H32N6O4S).

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. 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. 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.Synthetic Route of C23H32N6O4S

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

Volume changes in the proton ionization of amines in water. 1. Morpholines and piperazines was written by Cabani, S.;Mollica, V.;Lepori, L.;Lobo, S. T.. And the article was included in Journal of Physical Chemistry in 1977.Application In Synthesis of Piperazine Dihydrochloride This article mentions the following:

Apparent molar volumes, 桅v, at various concentrations in water at 25掳 of some cyclic bifunctional amines [morpholine, 4-methylmorpholine, piperazine, 1-methyl- and 1,4-dimethylpiperazine, 1,4-diazabicyclo[2.2.2]octane (triethylenediamine)] and their mono- and dihydrochlorides were determined The volume changes 螖V1掳 and 螖V2掳, involved in the 1st and 2nd proton ionizations from the protonated amines, were calculated from the limiting partial molar volumes V虆2掳. The volumes of ionization for the bifunctional cyclic amines were compared with those for the monofunctional amines ad the relationship between entropies and volumes of ionization was examined In the experiment, the researchers used many compounds, for example, Piperazine Dihydrochloride (cas: 142-64-3Application In Synthesis of Piperazine Dihydrochloride).

Piperazine Dihydrochloride (cas: 142-64-3) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 掳C and boils at 125鈥?30 掳C. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Application In Synthesis of Piperazine Dihydrochloride

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

Single-cell proteomic profiling identifies combined AXL and JAK1 inhibition as a novel therapeutic strategy for lung cancer was written by Taverna, Josephine A.;Hung, Chia-Nung;DeArmond, Daniel T.;Chen, Meizhen;Lin, Chun-Lin;Osmulski, Pawel A.;Gaczynska, Maria E.;Wang, Chiou-Miin;Lucio, Nicholas D.;Chou, Chih-Wei;Chen, Chun-Liang;Nazarullah, Alia;Lampkin, Shellye R.;Qiu, Lianqun;Bearss, David J.;Warner, Steven;Whatcott, Clifford J.;Mouritsen, Lars;Wade, Mark;Weitman, Steven;Mesa, Ruben A.;Kirma, Nameer B.;Chao, Wei-Ting;Huang, Tim H.-M.. And the article was included in Cancer Research in 2020.Reference of 1341200-45-0 This article mentions the following:

Cytometry by time-of-flight (CyTOF) simultaneously measures multiple cellular proteins at the single-cell level and is used to assess intertumor and intratumor heterogeneity. Integrative transcriptome analyses were used to investigate how TP-0903, an AXL kinase inhibitor, influences redundant oncogenic pathways in metastatic lung cancer cells. CyTOF profiling revealed that AXL inhibition suppressed SMAD4/TGF尾 signaling and induced JAK1-STAT3 signaling to compensate for the loss of AXL. Interestingly, high JAK1-STAT3 was associated with increased levels of AXL in treatment-naive tumors. Tumors with high AXL, TGF尾, and JAK1 signaling concomitantly displayed CD133-mediated cancer stemness and hybrid epithelial-to-mesenchymal transition features in advanced-stage patients, suggesting greater potential for distant dissemination. Diffusion pseudotime anal. revealed cell-fate trajectories among four different categories that were linked to clinicopathol. features for each patient. Patient-derived organoids (PDO) obtained from tumors with high AXL and JAK1 were sensitive to TP-0903 and ruxolitinib (JAK inhibitor) treatments, supporting the CyTOF findings. This study shows that single-cell proteomic profiling of treatment-naive lung tumors, coupled with ex vivo testing of PDOs, identifies continuous AXL, TGF尾, and JAK1-STAT3 signal activation in select tumors that may be targeted by combined AXL-JAK1 inhibition. In the experiment, the researchers used many compounds, for example, 2-((5-Chloro-2-((4-((4-methylpiperazin-1-yl)methyl)phenyl)amino)pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide (cas: 1341200-45-0Reference of 1341200-45-0).

2-((5-Chloro-2-((4-((4-methylpiperazin-1-yl)methyl)phenyl)amino)pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide (cas: 1341200-45-0) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. 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.Reference of 1341200-45-0

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

Tandospirone suppresses impulsive action by possible blockade of the 5-HT_1A receptor was written by Ohmura, Yu;Kumamoto, Haruko;Tsutsui-Kimura, Iku;Minami, Masabumi;Izumi, Takeshi;Yoshida, Takayuki;Yoshioka, Mitsuhiro. And the article was included in Journal of Pharmacological Sciences (Tokyo, Japan) in 2013.Recommanded Product: 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 This article mentions the following:

Higher impulsivity is observed in several psychiatric disorders and could be a risk factor for drug addiction, criminal involvement, and suicide. Although the involvement of the 5-HT_1A receptor in impulsive behavior has been indicated, the effects of clin. relevant drugs have been rarely tested. In the present study, we examined whether (3aR,4S,7R,7aS)-rel-hexahydro-2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-4,7-methano-1H-isoindole-1,3(2H)-dione hydrochloride (tandospirone), an anxiolytic and a partial agonist of the 5-HT_1A receptor, could affect impulsive action in the 3-choice serial reaction time task. Rats were acutely administered tandospirone (0, 0.1, and 1 mg/kg, i.p.). Tandospirone decreased the number of premature responses, an index of impulsive action, in a dose-dependent manner. N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY100635; 0.3 mg/kg, s.c.), a 5-HT_1A receptor antagonist, did not reverse the suppressing effects of tandospirone on impulsive action. Moreover, a higher dose of WAY100635 (1 mg/kg, s.c.) suppressed impulsive action without tandospirone. Thus the effects of tandospirone on impulsivity might be due to the antagonistic action. Tandospirone could be a therapeutic candidate for impulsivity-related disorders. 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: 112457-95-1Recommanded Product: 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).

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. 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.Recommanded Product: 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

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

An MDM2 inhibitor achieves synergistic cytotoxic effects with adenoviruses lacking E1B55kDa gene on mesothelioma with the wild-type p53 through augmenting NFI expression was written by Nguyen, Thao Thi Thanh;Shingyoji, Masato;Hanazono, Michiko;Zhong, Boya;Morinaga, Takao;Tada, Yuji;Shimada, Hideaki;Hiroshima, Kenzo;Tagawa, Masatoshi. And the article was included in Cell Death & Disease in 2021.Computed Properties of C30H30Cl2N4O4 This article mentions the following:

A majority of mesothelioma specimens were defective of p14 and p16 expression due to deletion of the INK4A/ARF region, and the p53 pathway was consequently inactivated by elevated MDM2 functions which facilitated p53 degradaton. We investigated a role of p53 elevation by MDM2 inhibitors, nutlin-3a and RG7112, in cytotoxicity of replication-competent adenoviruses (Ad) lacking the p53-binding E1B55kDa gene (Ad-delE1B). We found that a growth inhibition by p53-activating Ad-delE1B was irrelevant to p53 expression in the infected cells, but combination of Ad-delE1B and the MDM2 inhibitor produced synergistic inhibitory effects on mesothelioma with the wild-type but not mutated p53 genotype. The combination augmented p53 phosphorylation, activated apoptotic but not autophagic pathway, and enhanced DNA damage signals through ATM-Chk2 phosphorylation. The MDM2 inhibitors facilitated production of the Ad progenies through augmented expression of nuclear factor I (NFI), one of the transcriptional factors involved in Ad replications. Knocking down of p53 with siRNA did not increase the progeny production or the NFI expression. We also demonstrated anti-tumor effects by the combination of Ad-delE1B and the MDM2 inhibitors in an orthotopic animal model. These data collectively indicated that upregulation of wild-type p53 expression contributed to cytotoxicity by E1B55kDa-defective replicative Ad through NFI induction and suggested that replication-competent Ad together with augmented p53 levels was a therapeutic strategy for p53 wild-type mesothelioma. In the experiment, the researchers used many compounds, for example, 4-(cis-4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one (cas: 548472-68-0Computed Properties of C30H30Cl2N4O4).

4-(cis-4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one (cas: 548472-68-0) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. 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 C30H30Cl2N4O4

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

Separation of the main impurity demethylgatifloxacin from gatifloxacin and its synthesis and identification was written by Wang, Xiuzhen;Wang, Xintu;Wang, Erhua. And the article was included in Zhongguo Yaoke Daxue Xuebao in 2003.Recommanded Product: 1-Cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid This article mentions the following:

The main impurity of gatifloxacin was identified. Demethylgatifloxacin was synthesized in four steps from Et 2-(3-methoxy-2,4,5-trifluorobenzoyl)-3-(cyclopropylamino)acrylate through cyclization, chelation, N-piperazination, and hydrolysis, and identified by LC/MS, UV, ¹HNMR, ¹³CNMR, MS. 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: 112811-57-1Recommanded Product: 1-Cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid).

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. Simple N-substituted piperazines have been found in many drug molecules. 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: 1-Cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid

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

The relative bioavailability of paracetamol after rectal administration of suppositories containing a mixture of paracetamol, codeine phosphate and buclizine hydrochloride in healthy volunteers was written by Burgess, H. A.;Merrington, D. M.;Oliver, W. J.;Thomson, A.;Rogers, H. J.. And the article was included in Current Medical Research and Opinion in 1985.Reference of 129-74-8 This article mentions the following:

The bioavailability of paracetamol (I) [103-90-2] from suppositories containing I, codeine聽phosphate聽聽[52-28-8], and buclizine-HCl聽聽[129-74-8] was studied in healthy volunteers. No significant difference in bioavailability between suppositories stored 6 and 30 mo. was found. Mean peak plasma concentrations for 6 and 30 mo old suppositories were 4.75 mg/L and 4.6 mg/L, resp., mean elimination half-life was 4.4 h and 3.73 h, resp. and areas under the concentration-time curve were 2273 mg L^-1 min and 2338 mg L^-1 min, resp. These bioavailability data were similar to those obtained in a study where suppositories containing only I were used, indicating that the presence of codeine and buclizine in the suppository formulation did not affect the absorption of I. In the experiment, the researchers used many compounds, for example, 1-(4-(tert-Butyl)benzyl)-4-((4-chlorophenyl)(phenyl)methyl)piperazine dihydrochloride (cas: 129-74-8Reference of 129-74-8).

1-(4-(tert-Butyl)benzyl)-4-((4-chlorophenyl)(phenyl)methyl)piperazine dihydrochloride (cas: 129-74-8) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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).Reference of 129-74-8

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