Category: piperazines

Hitting a Moving Target: Simulation and Crystallography Study of ATAD2 Bromodomain Blockers was written by Dolbois, Aymeric;Batiste, Laurent;Wiedmer, Lars;Dong, Jing;Brutsch, Manuela;Huang, Danzhi;Deerain, Nicholas M.;Spiliotopoulos, Dimitrios;Cheng-Sanchez, Ivan;Laul, Eleen;Nevado, Cristina;Sledz, Pawel;Caflisch, Amedeo. And the article was included in ACS Medicinal Chemistry Letters in 2020.Name: 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid This article mentions the following:

Small mol. ligand binding to the ATAD2 bromodomain is investigated here through the synergistic combination of mol. dynamics and protein crystallog. A previously unexplored conformation of the binding pocket upon rearrangement of the gatekeeper residue Ile1074 has been found. Further, our investigations reveal how minor structural differences in the ligands result in binding with different plasticity of the ZA loop for this difficult-to-drug bromodomain. In the experiment, the researchers used many compounds, for example, 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (cas: 149057-19-2Name: 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid).

4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (cas: 149057-19-2) 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. 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-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid

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

Synthesis and polymerization of active ester monomers based on 4-vinylbenzoic acid was written by Nilles, Katja;Theato, Patrick. And the article was included in European Polymer Journal in 2007.Name: 1-Propylpiperazine This article mentions the following:

Nine active ester monomers based on 4-vinylbenzoic acid have been synthesized. Under free radical polymerization conditions these monomers could successfully be polymerized yielding reactive polymers with mol. weights of around M_n = 20.000-50.000 g/mol and mol. weight distributions M_w/M_n of around or below 2 in good yields. Polymer analogous reactions with amines have been investigated by time-resolved FT-IR spectroscopy and it was found that especially poly(pentafluorophenyl 4-vinylbenzoate) featured a significant reactivity, such that polymer analogous reactions proceeded quant. with amines within less than 5 min at 0°. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Name: 1-Propylpiperazine).

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 formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Name: 1-Propylpiperazine

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

Synthesis and cytotoxicity evaluation of (tetrahydro-β-carboline)-1,3,5-triazine hybrids as anticancer agents was written by Kumar, Ravi;Gupta, Leena;Pal, Pooja;Khan, Shahnawaz;Singh, Neetu;Katiyar, Sanjay Babu;Meena, Sanjeev;Sarkar, Jayanta;Sinha, Sudhir;Kanaujiya, Jitendra Kumar;Lochab, Savita;Trivedi, Arun Kumar;Chauhan, Prem M. S.. And the article was included in European Journal of Medicinal Chemistry in 2010.Electric Literature of C7H16N2 This article mentions the following:

A series of tetrahydro-β-carbolines and 1,3,5-triazine hybrids have been synthesized and evaluated for their cytotoxicity against a panel of eight human cancer cell lines and normal human fibroblasts (NIH3T3). It led us to discovery of three racemic compounds which are selectively cytotoxic towards KB (oral cancer) cell line with IC₅₀ values of 105.8, 664.7 and 122.2 nM, resp.; their enantiopure forms are less active and not selective. Enantiopure compound I (R = N-methylpiperazine) showed 2.5 times more selectivity towards MCF7 cells over normal fibroblast NIH3T3 cells with an IC₅₀ value of 740 nM, also arrests cell cycle in G₁ phase and induces apoptosis in MCF7 and MDA MB231cell lines. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Electric Literature of C7H16N2).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. 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 C7H16N2

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

Quinoxalinone inhibitors of the lectin DC-SIGN was written by Mangold, Shane L.;Prost, Lynne R.;Kiessling, Laura L.. And the article was included in Chemical Science in 2012.Reference of 21867-64-1 This article mentions the following:

The C-type lectin dendritic cell-specific intercellular adhesion mol. 3-grabbing nonintegrin (DC-SIGN) can serve as a docking site for pathogens on the surface of dendritic cells. Pathogen binding to DC-SIGN can have diverse consequences for the host. DC-SIGN can facilitate HIV-1 dissemination, but the interaction of Mycobacterium tuberculosis with DC-SIGN is important for host immunity. The ability of pathogens to target DC-SIGN provides impetus to identify ligands that can perturb these interactions. Here, we describe the first stable small mol. inhibitors of DC-SIGN. These inhibitors were derived from a collection of quinoxalinones, which were assembled using a tandem cross metathesis-hydrogenation sequence. To assess the ability of these small mols. to block DC-SIGN-mediated glycan adhesion and internalization, we developed a sensitive flow cytometry assay. Our results reveal that the quinoxalinones are effective inhibitors of DC-SIGN-glycan interactions. These compounds block both glycan binding to cells and glycan internalization. We anticipate that these non-carbohydrate inhibitors can be used to elucidate the role of DC-SIGN in pathogenesis and immune function. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Reference of 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) 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. Reference of 21867-64-1

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

Synthesis and SAR of piperazinyl-N-phenylbenzamides as inhibitors of hepatitis C virus RNA replication in cell culture was written by Conte, Immacolata;Giuliano, Claudio;Ercolani, Caterina;Narjes, Frank;Koch, Uwe;Rowley, Michael;Altamura, Sergio;De Francesco, Raffaele;Neddermann, Petra;Migliaccio, Giovanni;Stansfield, Ian. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2009.Computed Properties of C16H22N2O4 This article mentions the following:

The RNA replication machinery of HCV is a multi-subunit membrane-associated complex. NS5A has emerged as an active component of HCV replicase, possibly involved in regulation of viral replication and resistance to the antiviral effect of interferon. Substituted piperazinyl-N-(aryl)benzamides were prepared as potent inhibitors of HCV replication exerted via modulation of the dimerization of NS5A. 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).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) 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.Computed Properties of C16H22N2O4

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

Ruthenium catalyzed β-C(sp³)-H functionalization on the ‘privileged’ piperazine nucleus was written by Murugesh, V.;Bruneau, Christian;Achard, Mathieu;Sahoo, Apurba Ranjan;Sharma, Gangavaram V. M.;Suresh, Surisetti. And the article was included in Chemical Communications (Cambridge, United Kingdom) in 2017.HPLC of Formula: 21867-64-1 This article mentions the following:

β-C(sp³)-H functionalization on the ‘privileged’ piperazine nucleus was disclosed using ruthenium catalysis. The ruthenium catalyzed synthesis of a variety of piperazine fused indoles I [R = Me, Et, n-Pr; R¹ = H, 9-Cl, 7-CF₃, etc.] from ortho-piperazinyl (hetero)aryl aldehydes was presented. This transformation was not limited to only ortho-piperazinyl aromatic aldehydes as N-heteroaryl piperazine like 8-methyl-2-(4-methyl-piperazin-1-yl)quinoline-3-carbaldehyde also served as a good substrate in this transformation to afford the corresponding piperazine fused aza-indole system in good yield. This transformation took place via the dehydrogenation of piperazine followed by an intramol. nucleophilic addition of the transient enamine moiety onto the carbonyl group and aromatization cascade. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1HPLC of Formula: 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) 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.HPLC of Formula: 21867-64-1

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

Piperazine compounds. III. Syntheses of 1-piperazinylalkyltheophylline derivatives was written by Ikeda, Yoshiaki. And the article was included in Yakugaku Zasshi in 1969.Application of 21867-64-1 This article mentions the following:

The following I were prepared by known methods (R, X, % yield, and b.p./mm. or m.p. given): Pr, H, 42, 45.5-7°/10 (dipicrate, m. 234-6.5°); p-ClC6H4CH2, CH2CH(OH)CHCl, 83, 78-9°. Theophylline (II) (10.9 g.), 2.3 g. NaOH, and 42 ml. H2O treated at 80-5° with 12.5 ml. BrCH2CH2Br in 20 ml. iso-PrOH over 1 hr. and refluxed 7-8 hrs. gave 48% QCH2CH2Br (Q = 7-theophyllinyl in this abstract) (III), m. 144-5°. The following IV were prepared by heating III with 2 moles I (X = H) 7-8 hrs. in EtOH (R, % yield, and m.p. given): Et, 98, 93-4°; Pr, 70, – (2HCl salt m. 278-80°); allyl, 82, 87-8°; Bu, 95, 77-9°; HOCH2CH2, 68, – (2HCl.H2O salt m. 268-9°); HO(CH2)3, 47, 114-15°; Ph-CH2 (IVa), 95, 120-1°; p-ClC6H4CH2, 70, 152-2.5°; o-ClC6H4-CH2, 72, 159.5-60.5; m-ClC6H4CH2, 71, 127.5-9.5°; PhCH2CH2, 73, – (2HCl salt m. 264-6°); EtO2C, 84, 135.5-7.5°; Ac, 71, 140-1°; Bz, 90, 184-5°. Similarly prepared were V.2HCl (same data given): Pr, 96, 302-3°; allyl, 73, 269-70°; Bu, 61, – (base m. 70-1°); HOCH2CH2, 92, – (base m. 80-2°); HO(CH2)3, 82, 108-11°; PhCH2, 95, 285-6°. The following VI were prepared by heating 7-(2,3-epoxypropyl)theophylline with 1.2 moles I (X = H) in EtOH (besides a little QCH2CH(OH)CH2Q, m. 267-8°) (same data given): Et, 30, 145-5.5°; Pr, 65, 153-4°; allyl, 45, 140.5-1°; Bu, 74, 146-7°; HOCH2CH2, 82, 153.5-4.5°; HO(CH2)3, 85, 164-5°; PhCH2, 76, 175-5.5°; p-ClC6H4CH2, 80, 156-7°; o-ClC6H4CH2, 84, 169-70°; m-Cl-C6H4CH2 (VIa), 75, 160-60.5°; p-MeOC6H4CH2, 71, 151.5-2.5°; p-MeC6H4CH2, 73, 156.5-7.5°; p-iso-PrC6H4CH2, 80, 175-6°; PhCH2CH2, 70, 148.5-9.5°; HCO, 75, 107-10; EtO2C (VIb), 84, 178-9°; Ac, 88, 174.5-6.5°; Bz, 80, 155-6°. O-Acylation gave VII (Z = Ac or Bz) (R and m.p. of acetate and of benzoate given): PhCH2, 153-4°, 148-9.5°; p-ClC6H4CH2, 145-7°, 155-7°; o-ClC6H4CH2, 158-9°, 141-2°; m-ClC6H4CH2, 152-3°, 139.5-40°; p-MeC6H4CH2, -, 122-3°; p-iso-PrC6H4-CH2, 134-5°, 90.5-1.5°; PhCH2CH2, 133-4°, 155.5-6.5°; EtO2C, 128-9°, 176-7°. Piperazine hexahydrate (33 g.) and 5.9 g. K2CO3 in 200 ml. EtOH treated at reflux over 2 hrs. with 24.5 g. III, clarified, and treated with p-MeC6H4SO3H (Ts) gave 80% IV.2Ts (R = H) (IVb), m. 223-4°, and 15% VIII.2Ts (Y = CH2CH2), m. 289-90°. Also prepared were 81% VI.2Ts (R = H) (VIc), m. 250-1.5°, and 10% VIII.2Ts (Y = CH2CHOHCH2), m. 274-6°, converted to VIII.2Ts (Y = CH2CHOAcCH2), m. 264-5°. IVa was also prepared in 70 or 75% yield by heating II, I (R = PhCH2, X = CH2CH2Cl), and K2CO3 in EtOH or by heating IVb, PhCH2Cl, and Et3N in EtOH, resp. Similar alkylation of VIc gave 79% VIa or the following VI (R, % yield, and m.p. given): α-naphthylmethyl, 62, – (2HCl salt, m. 272-4°); 2-pyridylethyl, 76 (heated with 2-vinylpyridine and AcOH in EtOH), 169.5-70.5°. Hydrolysis of VIb in 35% HBr-AcOH 4 hrs. at 60° also gave 90% VIc. Similarly, hydrolysis with concentrated HCl 20-5 hrs. at reflux removed Ac and Bz groups and gave 68-75% VIc. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Application of 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Application of 21867-64-1

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

Discovery of BAY-985, a Highly Selective TBK1/IKKε Inhibitor was written by Lefranc, Julien;Schulze, Volker Klaus;Hillig, Roman Christian;Briem, Hans;Prinz, Florian;Mengel, Anne;Heinrich, Tobias;Balint, Jozsef;Rengachari, Srinivasan;Irlbacher, Horst;Stoeckigt, Detlef;Boemer, Ulf;Bader, Benjamin;Gradl, Stefan Nikolaus;Nising, Carl Friedrich;von Nussbaum, Franz;Mumberg, Dominik;Panne, Daniel;Wengner, Antje Margret. And the article was included in Journal of Medicinal Chemistry in 2020.Reference of 21867-64-1 This article mentions the following:

The serine/threonine kinase TBK1 (TANK-binding kinase 1) and its homolog IKKε are noncanonical members of the inhibitor of the nuclear factor κB (IκB) kinase family. These kinases play important roles in multiple cellular pathways and, in particular, in inflammation. Herein, we describe our investigations on a family of benzimidazoles and the identification of the potent and highly selective TBK1/IKKε inhibitor BAY-985. BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 and displays antiproliferative efficacy in the melanoma cell line SK-MEL-2 but showed only weak antitumor activity in the SK-MEL-2 human melanoma xenograft model. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Reference of 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. 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.Reference of 21867-64-1

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

gem-Difluoromethylene Alkyne-Enabled Diverse C-H Functionalization and Application to the on-DNA Synthesis of Difluorinated Isocoumarins was written by Gao, Hui;Lin, Shuang;Zhang, Shuning;Chen, Weijie;Liu, Xiawen;Yang, Guang;Lerner, Richard A.;Xu, Hongtao;Zhou, Zhi;Yi, Wei. And the article was included in Angewandte Chemie, International Edition in 2021.Computed Properties of C16H22N2O4 This article mentions the following:

Using gem-difluoromethylene alkynes as effectors, unprecedented diverse C-H activation/[4+2] annulations of simple benzoic acids are reported. The chemodivergent reaction outcomes are well-tuned by Rh/Ir-catalyzed system; in the Rh^III catalysis, 3-alkenyl-1H-isochromen-1-one and 3,4-dialkylideneisochroman-1-one skeletons are afforded in a solvent-dependent manner (e.g., benzoic acid + I → II (in MeOH)/III (in TFE)) under whereas difluoromethylene-substituted 1H-isochromen-1-ones (IV) are generated under the Ir^III-catalyzed system. Mechanistic studies revealed that unusually double β-F eliminations and fluorine effect-induced regioselective reductive elimination are independently involved to enable distinct reaction modes for divergent product formations. Besides, synthetic application in both the derivatization of obtained diene products and the on-DNA synthesis of DNA-tagged difluorinated isocoumarin have been demonstrated, which manifested great potential for synthetic utility of the developed protocols. 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).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) 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.Computed Properties of C16H22N2O4

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

Fragment-Based Design of Symmetrical Bis-benzimidazoles as Selective Inhibitors of the Trimethoprim-Resistant, Type II R67 Dihydrofolate Reductase was written by Bastien, Dominic;Ebert, Maximilian C. C. J. C.;Forge, Delphine;Toulouse, Jacynthe;Kadnikova, Natalia;Perron, Florent;Mayence, Annie;Huang, Tien L.;Vanden Eynde, Jean Jacques;Pelletier, Joelle N.. And the article was included in Journal of Medicinal Chemistry in 2012.Synthetic Route of C16H22N2O4 This article mentions the following:

The continuously increasing use of trimethoprim as a common antibiotic for medical use and for prophylactic application in terrestrial and aquatic animal farming has increased its prevalence in the environment. This has been accompanied by increased drug resistance, generally in the form of alterations in the drug target, dihydrofolate reductase (DHFR). The most highly resistant variants of DHFR are known as type II DHFR, among which R67 DHFR is the most broadly studied variant. We report the first attempt at designing specific inhibitors to this emerging drug target by fragment-based design. The detection of inhibition in R67 DHFR was accompanied by parallel monitoring of the human DHFR, as an assessment of compound selectivity. By those means, small aromatic mols. of 150-250 g/mol (fragments) inhibiting R67 DHFR selectively in the low millimolar range were identified. More complex, sym. bis-benzimidazoles and a bis-carboxyphenyl were then assayed as fragment-based leads, which procured selective inhibition of the target in the low micromolar range (K_i = 2-4 μM). The putative mode of inhibition is discussed according to mol. modeling supported by in vitro tests. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Synthetic Route of C16H22N2O4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) 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. 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.Synthetic Route of C16H22N2O4

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