Heterocyclic Building Blocks-piperidine

Synthesis and thermal reactions of 2-haloethylamine nickel(II) complexes was written by Ukraintsev, V. B.;Radzhabov, T.;Yakovlev, S. V.;Kukushkin, Yu. N.. And the article was included in Zhurnal Obshchei Khimii in 1987.Product Details of 142-64-3 This article mentions the following:

[Ni(NH₂CH₂CH₂X)₄X₂] (I; X = Cl, Br) were prepared by reaction of (XCH₂CH₂NH₃)₄[NiX₄] with NaOH. Solid-phase thermal reactions of I gave Ni(NH₂CH₂CH₂NHCH₂CH₂X)₂X₂ at 100-140° and piperazine dihydrohalide and NiX₂ at 160-210°. In the experiment, the researchers used many compounds, for example, Piperazine Dihydrochloride (cas: 142-64-3Product Details of 142-64-3).

Piperazine Dihydrochloride (cas: 142-64-3) 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.Product Details of 142-64-3

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

A single-cell nanocoating of probiotics for enhanced amelioration of antibiotic-associated diarrhea was written by Pan, Jiezhou;Gong, Guidong;Wang, Qin;Shang, Jiaojiao;He, Yunxiang;Catania, Chelsea;Dan, Birnbaum;Li, Yifei;Jia, Zhijun;Zhang, Yaoyao;Joshi, Neel S.;Guo, Junling. And the article was included in Nature Communications in 2022.Computed Properties of C17H18FN3O3 This article mentions the following:

The gut microbiota represents a large community of microorganisms that play an important role in immune regulation and maintenance of homeostasis. Living bacteria receive increasing interest as potential therapeutics for gut disorders, because they inhibit the colonization of pathogens and pos. regulate the composition of bacteria in gut. However, these treatments are often accompanied by antibiotic administration targeting pathogens. In these cases, the efficacy of therapeutic bacteria is compromised by their susceptibility to antibiotics. Here, we demonstrate that a single-cell coating composed of tannic acids and ferric ions, referred to as nanoarmor, can protect bacteria from the action of antibiotics. The nanoarmor protects both Gram-pos. and Gram-neg. bacteria against six clin. relevant antibiotics. The multiple interactions between the nanoarmor and antibiotic mols. allow the antibiotics to be effectively absorbed onto the nanoarmor. Armored probiotics have shown the ability to colonize inside the gastrointestinal tracts of levofloxacin-treated rats, which significantly reduced antibiotic-associated diarrhea (AAD) resulting from the levofloxacin-treatment and improved some of the pre-inflammatory symptoms caused by AAD. This nanoarmor strategy represents a robust platform to enhance the potency of therapeutic bacteria in the gastrointestinal tracts of patients receiving antibiotics and to avoid the neg. effects of antibiotics in the gastrointestinal tract. In the experiment, the researchers used many compounds, for example, 1-Cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (cas: 85721-33-1Computed Properties of C17H18FN3O3).

1-Cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (cas: 85721-33-1) 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. Computed Properties of C17H18FN3O3

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

Bevacizumab augments the antitumor efficacy of infigratinib in hepatocellular carcinoma was written by Le, Thi Bich Uyen;Vu, Thanh Chung;Ho, Rebecca Zhi Wen;Prawira, Aldo;Wang, Lingzhi;Goh, Boon Cher;Huynh, Hung. And the article was included in International Journal of Molecular Sciences in 2020.Formula: C26H31Cl2N7O3 This article mentions the following:

The fibroblast growth factor (FGF) signaling cascade is one of the key signaling pathways in hepatocellular carcinoma (HCC). FGF has been shown to augment vascular endothelial growth factor (VEGF)-mediated HCC development and angiogenesis, as well as to potentially lead to resistance to VEGF/VEGF receptor (VEGFR)-targeted agents. Thus, novel agents targeting FGF/FGF receptor (FGFR) signalling may enhance and/or overcome de novo or acquired resistance to VEGF-targeted agents in HCC. Mice bearing high- and low-FGFR tumors were treated with Infigratinib (i.e., a pan-FGFR kinase inhibitor) and/or Bevacizumab (i.e., an angiogenesis inhibitor). The antitumor activity of both agents was assessed individually or in combination. Tumor vasculature, intratumoral hypoxia, and downstream targets of FGFR signaling pathways were also investigated. Infigratinib, when combined with Bevacizumab, exerted a synergistic inhibitory effect on tumor growth, invasion, and lung metastasis, and it significantly improved the overall survival of mice bearing FGFR-dependent HCC. Infigratinib/Bevacizumab promoted apoptosis, inhibited cell proliferation concomitant with upregulation of p27, and reduction in the expression of FGFR2-4, p-FRS-2, p-ERK1/2, p-p70S6K/4EBP1, Cdc25C, survivin, p-Cdc2, and p-Rb. Combining Infigratinib/Bevacizumab may provide therapeutic benefits for a subpopulation of HCC patients with FGFR-dependent tumors. A high level of FGFR-2/3 may serve as a potential biomarker for patient selection to Infigratinib/Bevacizumab. In the experiment, the researchers used many compounds, for example, 3-(2,6-Dichloro-3,5-dimethoxyphenyl)-1-(6-((4-(4-ethylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)-1-methylurea (cas: 872511-34-7Formula: C26H31Cl2N7O3).

3-(2,6-Dichloro-3,5-dimethoxyphenyl)-1-(6-((4-(4-ethylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)-1-methylurea (cas: 872511-34-7) 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 formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Formula: C26H31Cl2N7O3

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

Application of in vitro drug metabolism studies in chemical structure optimization for the treatment of fibrodysplasia ossificans progressiva (FOP) was written by Padilha, Elias C.;Wang, Jianyao;Kerns, Ed;Lee, Arthur;Huang, Wenwei;Jiang, Jian-kang;McKew, John;Abdul Mutlib;Peccinini, Rosangela G.;Yu, Paul B.;Sanderson, Philip;Xu, Xin. And the article was included in Frontiers in Pharmacology in 2019.Electric Literature of C25H22N6 This article mentions the following:

Currently no approved treatment exists for fibrodysplasia ossificans progressiva (FOP) patients, and disease progression results in severe restriction of joint function and premature mortality. LDN-193189 has been demonstrated to be efficacious in a mouse FOP disease model after oral administration. To support species selection for drug safety evaluation and to guide structure optimization for back-up compounds, in-vitro metabolism of LDN-193189 was investigated in liver microsome and cytosol fractions of mouse, rat, dog, rabbit, monkey and human. Metabolism studies included anal. of reactive intermediate formation using glutathione and potassium cyanide (KCN) and anal. of non-P 450 mediated metabolites in cytosol fractions of various species. Metabolite profiles and metabolic soft spots of LDN-193189 were elucidated using LC/UV and mass spectral techniques. The in-vitro metabolism of LDN-193189 was significantly dependent on aldehyde oxidase, with formation of the major NIH-Q55 metabolite. The piperazinyl moiety of LDN-193189 was liable to NADPH-dependent metabolism which generated reactive iminium intermediates, as confirmed through KCN trapping experiments, and aniline metabolites (M337 and M380), which brought up potential drug safety concerns. Subsequently, strategies were employed to avoid metabolic liabilities leading to the synthesis of Quinoline, 2-methyl-4-6-[[4-(1-piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-; 6-({[2-(piperidin-1-yl)ethoxy]pyridin-3-yl}pyrazolo[1,5-a]pyrimidin-3-yl)quinoline and 2-methyl-4-(6-{6-[2-(piperidin-1-yl)ethoxy]pyridin-3-yl}pyrazolo[1,5-a]pyrimidin-3-yl)quinoline. This study demonstrated the importance of metabolite identification for the discovery of novel and safe drug candidates for the treatment of FOP and helped medicinal chemists steer away from potential metabolic liabilities. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Electric Literature of C25H22N6).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Electric Literature of C25H22N6

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

Development of predictive retention-activity relationship models of antipsychotic drugs by micellar liquid chromatography was written by Martin-Biosca, Y.;Molero-Monfort, M.;Sagrado, S.;Villanueva-Camanas, R. M.;Medina-Hernandez, M. J.. And the article was included in Biomedical Chromatography in 1999.Name: N,N-Dimethyl-10-(3-(4-methylpiperazin-1-yl)propyl)-10H-phenothiazine-2-sulfonamide This article mentions the following:

The predictive and interpretative capability of quant. chromatog. retention-biol. activity models is supported by the fact that in adequate exptl. conditions the solute partitioning into the chromatog. system can emulate the solute partitioning into lipid bilayers of biol. membranes, which is the basis of drug and metabolite uptake, passive transport across membranes and bioaccumulation. The use of micellar solutions of Brij35 as mobile phases in reversed liquid chromatog. has proven to be valid in predicting some biol. activities of different kinds of drugs. In this paper, the correlations between the logarithm of capacity factors and pharmacokinetic, preclin. pharmacol. and therapeutic efficacy parameters of phenothiazines are studied. Parabolic quant. retention-activity relationship models with predictive and interpretative ability have been obtained. 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: 316-81-4Name: 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. 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.Name: N,N-Dimethyl-10-(3-(4-methylpiperazin-1-yl)propyl)-10H-phenothiazine-2-sulfonamide

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

Polyimides containing nonaromatic nitrogen linkages was written by Feld, William A.;Le, Tieu Binh. And the article was included in Journal of Polymer Science, Part A: Polymer Chemistry in 1992.COA of Formula: C16H20N4 This article mentions the following:

Six polyimides were prepared by a 2-step polycondensation of 2,5-bis(4-aminophenyl)-2,5-diazahexane (I) and 1,4-bis(4-aminophenyl)-1,4-diazacyclohexane (II) with pyromellitic dianhydride (III), benzophenonetetracarboxylic dianhydride, and 5,5′-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]bis-1,3-isobenzofurandione. The effect of structure on the glass transition was studied by DSC, and DSC thermograms failed to indicate any distinct transitions <450°; however, I–III polyimide showed a slight break in its DSC curve at 233°. The m.p. of model compounds (prepared from phthalic anhydride) did not differ by as much as those of the free amines, 303-304 and 386° (DSC), resp. In the experiment, the researchers used many compounds, for example, 4,4′-(Piperazine-1,4-diyl)dianiline (cas: 7479-12-1COA of Formula: C16H20N4).

4,4′-(Piperazine-1,4-diyl)dianiline (cas: 7479-12-1) 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.COA of Formula: C16H20N4

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

Brexpiprazole Pharmacokinetics in CYP2D6 Poor Metabolizers: Using Physiologically Based Pharmacokinetic Modeling to Optimize Time to Effective Concentrations was written by Elmokadem, Ahmed;Bruno, Christopher D.;Housand, Conrad;Jordie, Eric Burroughs;Chow, Christina R.;Lesko, Lawrence J.;Greenblatt, David J.. And the article was included in Journal of Clinical Pharmacology in 2022.Category: piperazines This article mentions the following:

Brexpiprazole is an oral antipsychotic agent indicated for use in patients with schizophrenia, or as adjunctive treatment for major depressive disorder. As cytochrome P 450 (CYP) 2D6 contributes significantly to brexpiprazole metabolism, there is a label-recommended 50% reduction in dose among patients with the CYP2D6 poor metabolizer phenotype. This study uses a whole-body physiol. based pharmacokinetic (PBPK) model to compare the pharmacokinetics of brexpiprazole in patients known to be extensive metabolizers (EMs) and poor metabolizers (PMs). A PBPK model was constructed, verified, and validated against brexpiprazole clin. data, and simulations of 500 subjects were performed to establish the median time to effective concentrations in EMs and PMs. The PBPK simulations captured brexpiprazole PK well and demonstrated significant differences in the time to effective concentrations between EMs and PMs according to the label-recommended titration Addnl., these simulations suggest that CYP2D6 PMs consistently achieve lower min. concentrations during the dosing interval than CYP2D6 EMs. Simulations using an alternative dosing strategy of twice-daily dosing (as opposed to once daily) in PMs during the first week of brexpiprazole dosing yielded more consistent plasma concentrations between EMs and PMs, without exceeding the area under the plasma concentration-time curve observed in the EMs. Taken together, the results of these PBPK simulations suggest that product labeling for brexpiprazole titration in CYP2D6 PMs likely overcompensates for the decreased clearance seen in this population. We propose an alternative dosing strategy that decreases the time to effective concentrations and recommend a reevaluation of steady-state PK in this population to potentially allow for higher daily doses in CYP2D6 PMs. 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: 913611-97-9Category: piperazines).

7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one (cas: 913611-97-9) 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. 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

Discovery of DA-1229: A potent, long acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes was written by Kim, Heung Jae;Kwak, Woo Young;Min, Jong Pil;Lee, Jae Young;Yoon, Tae Hyun;Kim, Ha Dong;Shin, Chang Yell;Kim, Mi Kyung;Choi, Song Hyen;Kim, Hae Sun;Yang, Eun Kyoung;Cheong, Ye Hwang;Chae, Yu Na;Park, Kyung Jin;Jang, Ji Myun;Choi, Soo Jung;Son, Moon Ho;Kim, Soon Hoe;Yoo, Moohi;Lee, Bong Jin. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2011.SDS of cas: 78551-60-7 This article mentions the following:

A series of β-amino amide containing substituted piperazine-2-one derivatives was synthesized and evaluated as inhibitors of dipeptidyl peptidase-4 (DPP-4) for the treatment of type 2 diabetes. As results of intensive SAR study of the series, (R)-4-[(R)-3-amino-4-(2,4,5-trifluorophenyl)-butanoyl]-3-(t-butoxymethyl)-piperazin-2-one (DA-1229, I) displayed potent DPP-4 inhibition pattern in several animal models, was selected for clin. development. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate (cas: 78551-60-7SDS of cas: 78551-60-7).

tert-Butyl 4-benzyl-3-oxopiperazine-1-carboxylate (cas: 78551-60-7) 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.SDS of cas: 78551-60-7

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

Assessment of cytochrome P450 3A4-mediated drug-drug interactions for ipatasertib using a fit-for-purpose physiologically based pharmacokinetic model was written by Jing, Jing;Chen, Yuan;Musib, Luna;Jin, Jin Y.;Cheung, Kit Wun Kathy;Yoshida, Kenta;Sane, Rucha. And the article was included in Cancer Chemotherapy and Pharmacology in 2022.Electric Literature of C24H29N7O2 This article mentions the following:

Ipatasertib, a potent and highly selective small-mol. inhibitor of AKT, is currently under investigation for treatment of cancer. Ipatasertib is a substrate and a time-dependent inhibitor of CYP3A4. It exhibits non-linear pharmacokinetics at subclin. doses in the clin. dose escalation study. To assess the DDI risk of ipatasertib at the intended clin. dose of 400 mg with CYP3A4 inhibitors, inducers, and substrates, a fit-for-purpose physiol. based pharmacokinetic (PBPK) model of ipatasertib was developed. The PBPK model was constructed in Simcyp using in silico, in vitro, and clin. data and was optimized and verified using clin. data. The PBPK model described non-linear pharmacokinetics of ipatasertib and captured the magnitude of the observed clin. DDIs. Following repeated doses of 400 mg ipatasertib once daily (QD), the PBPK model predicted a 3.3-fold increase of ipatasertib exposure with itraconazole; a 2-2.5-fold increase with moderate CYP3A4 inhibitors, erythromycin and diltiazem; and no change with a weak CYP3A4 inhibitor, fluvoxamine. Addnl., in the presence of strong or moderate CYP3A4 inducers, rifampicin and efavirenz, ipatasertib exposures were predicted to decrease by 86% and 74%, resp. As a perpetrator, the model predicted that ipatasertib (400 mg) caused a 1.7-fold increase in midazolam exposure. This study demonstrates the value of using a fit-for-purpose PBPK model to assess the clin. DDIs for ipatasertib and to provide dosing strategies for the concurrent use of other CYP3A4 perpetrators or victims. 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: 571190-30-2Electric Literature of C24H29N7O2).

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. 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. Electric Literature of C24H29N7O2

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

Metabolism of ketoconazole and deacetylated ketoconazole by rat hepatic microsomes and flavin-containing monooxygenases was written by Rodriguez, Rosita J.;Acosta, Daniel Jr.. And the article was included in Drug Metabolism and Disposition in 1997.Product Details of 67914-61-8 This article mentions the following:

Ketoconazole (KT) has been reported to cause hepatotoxicity, which is probably not mediated through an immunoallergic mechanism. Although KT is extensively metabolized by hepatic microsomal enzymes, the nature, route of formation, and toxicity suspected metabolites are largely unknown. Recent reports indicate that N-deacetyl ketoconazole (DAK) is a major initial metabolite in mice, which, like lipophilic-4-alkylpiperazines, is susceptible to successive oxidative attacks on the N-1 position producing ring-opened dialdehydes. The rate of formation of DAK from hepatic rat microsomal incubations of KT was determined by HPLC. The rate of disappearance for KT was almost equal to the rate of DAK formation: 5.96 and 5.88 μM/h, resp. Also, the potential bioactivation of DAK was evaluation by measuring substrate activity of DAK with purified pig liver flavin-containing monooxygenase (FMO) and rat liver microsomes. Activity was measured by following DAK-dependent oxygen uptake polarog. at 37°C in pyrophosphate buffer (pH 8.8) containing the glucose-6-phosphate NADPH-generating system. The K_M‘s of DAK were 34.6 and 77.4 μM for the purified FMO and rat microsomal FMO, resp. Lastly, DAK was found to be metabolized by an NADPH-dependent rat liver microsomal monooxygenases at pH 8.8 to two metabolites as determined by HPLC. Heat inactivation of rat liver microsomal FMO abolished the formation of these metabolites from DAK. SKF-525A and anti-rat NADPH cytochrome P 450 reductase did not inhibit this reaction. These results suggest that deacetylation of KT yields a major product, DAK, for further metabolism by microsomal monooxygenases that seem to be FMO-related. In the experiment, the researchers used many compounds, for example, rel-1-(4-(((2R,4S)-2-((1H-Imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine (cas: 67914-61-8Product Details of 67914-61-8).

rel-1-(4-(((2R,4S)-2-((1H-Imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine (cas: 67914-61-8) 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 67914-61-8

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