Heterocyclic Building Blocks-piperazine

Combined serotonin (5-HT)_1A agonism, 5-HT_2A and dopamine D₂ receptor antagonism reproduces atypical antipsychotic drug effects on phencyclidine-impaired novel object recognition in rats was written by Oyamada, Yoshihiro;Horiguchi, Masakuni;Rajagopal, Lakshmi;Miyauchi, Masanori;Meltzer, Herbert Y.. And the article was included in Behavioural Brain Research in 2015.Electric Literature of C27H37N5O9 This article mentions the following:

Subchronic administration of an N-methyl-D-aspartate receptor (NMDAR) antagonist, e.g. phencyclidine (PCP), produces prolonged impairment of novel object recognition (NOR), suggesting they constitute a hypoglutamate-based model of cognitive impairment in schizophrenia (CIS). Acute administration of atypical, e.g. lurasidone, but not typical antipsychotic drugs (APDs), e.g. haloperidol, are able to restore NOR following PCP (acute reversal model). Furthermore, atypical APDs, when co-administered with PCP, have been shown to prevent development of NOR deficits (prevention model). Most atypical, but not typical APDs, are more potent 5-HT_2A receptor inverse agonists than dopamine (DA) D₂ antagonists, and have been shown to enhance cortical and hippocampal efflux and to be direct or indirect 5-HT_1A agonists in vivo. To further clarify the importance of these actions to the restoration of NOR by atypical APDs, sub-effective or non-EDs of combinations of the 5-HT_1A partial agonist (tandospirone), the 5-HT_2A inverse agonist (pimavanserin), or the D₂ antagonist (haloperidol), as well as the combination of all three agents, were studied in the acute reversal and prevention PCP models of CIS. Only the combination of all three agents restored NOR and prevented the development of PCP-induced deficit. Thus, this triple combination of 5-HT_1A agonism, 5-HT_2A antagonism/inverse agonism, and D₂ antagonism is able to mimic the ability of atypical APDs to prevent or ameliorate the PCP-induced NOR deficit, possibly by stimulating signaling cascades from D₁ and 5-HT_1A receptor stimulation, modulated by D₂ and 5-HT_2A receptor antagonism. 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: 112457-95-1Electric Literature of C27H37N5O9).

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. 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 C27H37N5O9

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

Effects of KB-2796, a new diphenylpiperazine calcium antagonist, on renal hemodynamics and urine formation in anesthetized dogs was written by Iwamoto, Takahiro;Morita, Tominori;Sukamoto, Takayuki;Ito, Keizo. And the article was included in Japanese Journal of Pharmacology in 1992.Computed Properties of C27H32Cl2F2N2O3 This article mentions the following:

The effects of KB-2796, a new calcium antagonist with a diphenylpiperazine moiety, on renal hemodynamics and urine formation were investigated in anesthetized dogs. I.v. infusion of KB-2796 (10, 30, and 100 μg/kg/min) decreased mean blood pressure (MBP) and renal vascular resistance (RVR) in a dose-dependent manner, but did not change renal blood flow (RBF). At the highest dose, glomerular filtration rate (GFR) and urine flow (UF) tended to decrease. Nicardipine (0.1, 0.3, and 1 μg/kg/min) also dose-dependently decreased MBP, RVR, GFR, and UF. When KB-2796 was infused into the renal artery at lower doses of 3 and 10 μg/kg/min, UF and urinary excretion of electrolytes increased without a significant change in RBF and GFR. Intrarenal infusion of KB-2796 at 30 μg/kg/min and nicardipine at 0.3 μg/kg/min produced a significant increase in GFR, RBF, UF, urinary excretion of electrolytes, and renin secretion rate. These results suggest that KB-2796 administered intrarenally exerts a diuretic action via tubular effects and the alteration of renal hemodynamics. However, its diuretic action might be masked by diminished urine formation via a reflex activation of the sympathetic nerves and/or via a reduction of renal perfusion pressure when it is administered systemically. In the experiment, the researchers used many compounds, for example, 1-(Bis(4-fluorophenyl)methyl)-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride (cas: 101477-54-7Computed Properties of C27H32Cl2F2N2O3).

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

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

Structure-Activity Relationship Studies of Sulfonylpiperazine Analogues as Novel Negative Allosteric Modulators of Human Neuronal Nicotinic Receptors was written by Henderson, Brandon J.;Carper, Daniel J.;Gonzalez-Cestari, Tatiana F.;Yi, Bitna;Mahasenan, Kiran;Pavlovicz, Ryan E.;Dalefield, Martin L.;Coleman, Robert S.;Li, Chenglong;McKay, Dennis B.. And the article was included in Journal of Medicinal Chemistry in 2011.Formula: C10H14N2O2S This article mentions the following:

Neuronal nicotinic receptors have been implicated in several diseases and disorders such as autism, Alzheimer’s disease, Parkinson’s disease, epilepsy, and various forms of addiction. To understand the role of nicotinic receptors in these conditions, it would be beneficial to have selective mols. that target specific nicotinic receptors in vitro and in vivo. Our laboratory has previously identified novel neg. allosteric modulators of human α4β2 (Hα4β2) and human α3β4 (Hα3β4) nicotinic receptors. The effects of novel sulfonylpiperazine analogs that act as neg. allosteric modulators in both Hα4β2 nAChRs and Hα3β4 nAChRs were investigated. This work, through structure-activity relationship (SAR) studies, describes the chem. features of these mols. that are important for both potency and selectivity on Hα4β2 nAChRs. In the experiment, the researchers used many compounds, for example, 1-(Phenylsulfonyl)piperazine (cas: 14172-55-5Formula: C10H14N2O2S).

1-(Phenylsulfonyl)piperazine (cas: 14172-55-5) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. 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.Formula: C10H14N2O2S

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

Re: 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 Altundag, Kadri. And the article was included in European Journal of Cancer in 2022.SDS of cas: 571190-30-2 This article mentions the following:

A polemic in response to Martin et al. (Eur J Cancer 2022;168:12e24) is given. In a recent publication by Martin et al. concluded that Overall survival with palbociclib plus endocrine therapy vs. capecitabine in postmenopausal patients with hormone receptor-pos., HER2-neg. metastatic breast cancer. Specifically, the visceral metastatic burden was not described. It would be expected that tumors with a higher visceral tumor burden are less likely to be responsive to treatment. Second, weak estrogen receptor status (close similarity to triple-neg. breast cancer) has not been reported. The author concluded that these tumors seem to be more likely to be responsive to capecitabine than the palbociclib combination. In the experiment, the researchers used many compounds, for example, 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (cas: 571190-30-2SDS of cas: 571190-30-2).

6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (cas: 571190-30-2) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. 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: 571190-30-2

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

Design and synthesis of C-12 dithiocarbamate andrographolide analogues as an anticancer agent was written by Arsakhant, Patcharee;Sirion, Uthaiwan;Chairoungdua, Arthit;Suksen, Kanoknetr;Piyachaturawat, Pawinee;Suksamrarn, Apichart;Saeeng, Rungnapha. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2020.Application of 27469-60-9 This article mentions the following:

A series of 21 new analogs of C-12 dithiocarbamate andrographolide, I (R = morpholino, 4-phenylpiperazino, dibenzylamino, etc.), was designed and synthesized from natural andrographolide isolated from a common Thai plant, Andrographis paniculata. The reaction used to manipulate the andrographolide scaffold was conducted in one pot under mild reaction conditions. This avoided toxic catalysts and gave nearly quant. yields of the new analogs, generally without byproducts and can be easily scaled up for industrial processing. All new analogs were evaluated against nine cancer cell lines; some analogs exhibited greater selective cytotoxic activity to MCF-7 cancer cell than that of the parent andrographolide and cancer drugs. In the experiment, the researchers used many compounds, for example, 4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9Application of 27469-60-9).

4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. 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 of 27469-60-9

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

Hydroxyzine-induced priapism. was written by Olson, Christopher;Jhawar, Archana;Elfessi, Zane;Doyle, Richard. And the article was included in The American journal of emergency medicine in 2021.Computed Properties of C21H27ClN2O2 This article mentions the following:

Priapism is a severe urologic condition requiring emergency management. Ischemic priapism is the most common subtype which is characterized by a long-lasting, painful, and rigid erection which can be caused by medications with alpha-adrenergic properties such as hydroxyzine. Typically, medication-induced priapism is reported at therapeutic doses and few case reports exist implicating medication overdose as the cause. We report a case of a patient taking hypercompliant doses of hydroxyzine hydrochloride for worsening insomnia (200-600 mg), including the night before admission. Blood-gas analysis of blood from the right corpora was completed and revealed a pH of 6.736, pCO₂ of 147, HCO₃ of 18.6 and a base excess of 17.7. The patient required aspiration and 560 μg of intracavernosal phenylephrine to achieve sustained detumescence. Emergency physicians should be aware of this risk as priapism is a medical emergency and this is the first report with hydroxyzine after an intentional overdose to our knowledge. In the experiment, the researchers used many compounds, for example, 2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol (cas: 68-88-2Computed Properties of C21H27ClN2O2).

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. 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 C21H27ClN2O2

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

TFAM downregulation promotes autophagy and ESCC survival through mtDNA stress-mediated STING pathway was written by Li, Yujia;Yang, Qi;Chen, Hui;Yang, Xiaotian;Han, Jingru;Yao, Xiaojuan;Wei, Xiajie;Si, Jiaoyang;Yao, Huanling;Liu, Hongliang;Wan, Lixin;Yang, Hushan;Wang, Yanming;Bao, Dengke. And the article was included in Oncogene in 2022.Application of 2086257-77-2 This article mentions the following:

The dynamics of mitochondrial biogenesis regulation is critical in maintaining cellular homeostasis for immune regulation and tumor prevention. Here, we report that mitochondrial biogenesis disruption through TFAM reduction significantly impairs mitochondrial function, induces autophagy, and promotes esophageal squamous cell carcinoma (ESCC) growth. We found that TFAM protein reduction promotes mitochondrial DNA (mtDNA) release into the cytosol, induces cytosolic mtDNA stress, subsequently activates the cGAS-STING signaling pathway, thereby stimulating autophagy and ESCC growth. STING depletion or mtDNA degradation by DNase I abrogates mtDNA stress response, attenuates autophagy, and decreases the growth of TFAM depleted cells. In addition, autophagy inhibitor also ameliorates mitochondrial dysfunction-induced activation of the cGAS-STING signaling pathway and ESCC growth. In conclusion, our results indicate that mtDNA stress induced by mitochondria biogenesis perturbation activates the cGAS-STING pathway and autophagy to promote ESCC growth, revealing an underappreciated therapeutic strategy for ESCC. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-hydroxy-3-(4-(4-(trifluoromethoxy)phenyl)piperazin-1-yl)butanamide (cas: 2086257-77-2Application of 2086257-77-2).

N-(4-Chlorophenyl)-4-hydroxy-3-(4-(4-(trifluoromethoxy)phenyl)piperazin-1-yl)butanamide (cas: 2086257-77-2) 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).Application of 2086257-77-2

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

Inhibitory effects of antipsychotic and anxiolytic agents on stress-induced degranulation of mouse dermal mast cells. was written by Shimoda, T;Liang, Z;Suzuki, H;Kawana, S. And the article was included in Clinical and experimental dermatology in 2010.Formula: C27H37N5O9 This article mentions the following:

BACKGROUND: Various psychological stresses induce degranulation of mast cells. It has been confirmed by animal experiments that stress induced by restraint promotes mast-cell degranulation in various organs, and that the degranulation is inhibited by pretreatment with corticotropin-releasing factor (CRF)-neutralizing antibodies, CRF receptor antagonists, and neurotensin (NT) antagonists. Previous studies have suggested that anxiety and fear induced in animals by psychological stressors promote the production and release of various neuropeptides and neurotransmitters, and induce degranulation of mast cells in several organs. AIM: To evaluate the effect of prior treatment with antipsychotic and anxiolytic agents to inhibit foot-shock (FS) stress-induced degranulation of mouse dermal mast cells. METHODS: Using a communication box system, FS was administered to mice and the degranulated dermal mast cells were counted. Chlorpromazine (2 or 4 mg/kg body weight), tandospirone (10 mg/kg body weight) or CRA1000, a selective non-peptidic CRF receptor type 1 antagonist (10 or 100 mg/kg body weight) was injected intraperitoneally 1 h before exposure to FS. RESULTS: After FS was administered, the number of dermal mast cells did not change. However, FS significantly increased the proportion of degranulated mast cells. Pretreatment of mice with chlorpromazine hydrochloride, an antipsychotic agent (2 or 4 mg/kg), or the anxiolytic agents tandospirone citrate (10 mg/kg) or CRA1000 (10 or 100 mg/kg), significantly inhibited the FS-induced mast-cell degranulation (P < 0.05, P < 0.01, P < 0.05, P < 0.05, and P < 0.05, respectively). CONCLUSIONS: Antipsychotic and anxiolytic agents may be effective treatments for stress-aggravated inflammatory skin diseases by inhibition of mast-cell degranulation. 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: 112457-95-1Formula: C27H37N5O9).

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. 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: C27H37N5O9

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

QSAR and 3D-QSAR of phenothiazine type multidrug resistance modulators in P388/ADR cells was written by Tsakovska, Ivanka M.. And the article was included in Bioorganic & Medicinal Chemistry in 2003.Recommanded Product: N,N-Dimethyl-10-(3-(4-methylpiperazin-1-yl)propyl)-10H-phenothiazine-2-sulfonamide This article mentions the following:

A series of 25 phenothiazines and structurally related compounds was investigated by QSAR (quant. structure activity relationship) and 3D-QSAR methods with respect to their MDR (multidrug resistance) reversing activity in P388/ADR- murine leukemia cell line resistant to ADR (adriamycin). The objective was to outline structural properties important for the investigated activity. Different measures for MDR reversal were used and compared. Two 3D-QSAR approaches were applied-CoMFA (comparative mol. field anal.) and CoMSIA (comparative mol. similarity indexes anal.). Both, neutral and protonated forms of the compounds were investigated. Mol. models with good predictive power were derived using a hydrophobic field alone and a combination of steric, hydrophobic, and hydrogen bond acceptor fields of the compounds In the combined models highest contribution of the hydrogen bond acceptor field was noticed. Thus, the dominant role of the hydrophobic and hydrogen bond acceptor fields for MDR reversing activity of the investigated compounds was demonstrated. The structural regions responsible for the differences in anti-MDR activity were analyzed in respect to their hydrophobic, hydrogen bond acceptor and steric nature. The results may direct design of new phenothiazines and related compounds as MDR modulators. In the experiment, the researchers used many compounds, for example, N,N-Dimethyl-10-(3-(4-methylpiperazin-1-yl)propyl)-10H-phenothiazine-2-sulfonamide (cas: 316-81-4Recommanded Product: N,N-Dimethyl-10-(3-(4-methylpiperazin-1-yl)propyl)-10H-phenothiazine-2-sulfonamide).

N,N-Dimethyl-10-(3-(4-methylpiperazin-1-yl)propyl)-10H-phenothiazine-2-sulfonamide (cas: 316-81-4) 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. 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: N,N-Dimethyl-10-(3-(4-methylpiperazin-1-yl)propyl)-10H-phenothiazine-2-sulfonamide

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

Consolidation of tumorous mandibular ramus defect during denosumab treatment for rapidly progressive metastatic breast cancer was written by Friedrich, Reinhard E.;Madani, Elika. And the article was included in Anticancer Research in 2021.COA of Formula: C23H30N8O This article mentions the following:

Pharmacol. inhibition of osteoclast activity is an essential component of oncol. therapy for patients with bone metastases. In rare cases, medication-related osteonecrosis of the jaws (MRONJ) is observed MRONJ can cause bone defects not inferior to primary or metastatic jaw neoplasms. Oral examination of patients on osteoclast-inhibiting medication aims to identify risk factors at an early stage and to initiate therapy. The current focus on osteoclast-inhibiting drugs in the maxillofacial region is MRONJ. Effects of the substances other than MRONJ are rarely reported. Case Report: The female patient with metastatic breast cancer had developed extensive osteolysis of the mandibular ramus at the time of initial diagnosis. The patient was treated with denosumab. Seven months later, a significant reduction in the mandibular osteolytic zone was recorded. However, known bone metastases from other sites had increased in size during multimodal therapy, and further metastases were recorded. Conclusion: Jaw metastasis can shrink under denosumab therapy. 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: 1211441-98-3COA of Formula: C23H30N8O).

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 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.COA of Formula: C23H30N8O

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