Category: piperazines

Name: Abt-724On September 23, 2013 ,《Computational Profiling of Bioactive Compounds Using a Target-Dependent Composite Workflow》 was published in Journal of Chemical Information and Modeling. The article was written by Meslamani, Jamel; Bhajun, Ricky; Martz, Francois; Rognan, Didier. The article contains the following contents:

Computational target fishing is a chemoinformatic method aimed at determining main and secondary targets of bioactive compounds in order to explain their mechanism of action, anticipate potential side effects, or repurpose existing drugs for novel therapeutic indications. Many existing successes in this area have been based on a use of a single computational method to estimate potentially new target-ligand associations We herewith present an automated workflow using several methods to optimally browse target-ligand space according to existing knowledge on either ligand and target space under investigation. The protocol uses four ligand-based (SVM classification, SVR affinity prediction, nearest neighbors interpolation, shape similarity) and two structure-based approaches (docking, protein-ligand pharmacophore match) in series, according to well-defined ligand and target property checks. The workflow was remarkably accurate (72%) in identifying the main target of 189 clin. candidates and proposed two novel off-targets which could be exptl. validated. Rolofylline, an adenosine A1 receptor antagonist, was confirmed to inhibit phosphodiesterase 5 with a moderate affinity (IC50 = 13.8 μM). More interestingly, we describe a strong binding (IC50 = 142 nM) of a claimed selective phosphodiesterase 10 A inhibitor (PF-2545920) with the cysteinyl leukotriene type 1 G protein-coupled receptor. The results came from multiple reactions, including the reaction of Abt-724(cas: 70006-24-5Name: Abt-724)

Abt-724(cas: 70006-24-5) belongs to piperazines. 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).Name: Abt-724

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

Name: 1-(3-(Methylsulfonyl)propyl)piperazine dihydrochlorideOn November 18, 2011 ,《Application of PAT tools for the safe and reliable production of a dihydro-1H-imidazole》 appeared in Organic Process Research & Development. The author of the article were Barrios Sosa, Ana C.; Conway, Ryan; Williamson, R. Thomas; Suchy, James P.; Edwards, William; Cleary, Thomas. The article conveys some information:

The application of two Process Anal. Technol. (PAT) tools was studied and implemented for the safe and reliable synthesis of an advanced intermediate (4S,5R-7) (I) of a member of the dihydro-1H-imidazole class of compounds Real time data were generated using ReactIR to track the complete breakdown of phosgene precursors to phosgene and confirm the absence of these hazardous materials prior to batch transfer operations. In addition, the chiral resolution by crystallization of rac7 was monitored by a Lasentec FBRM probe-based system. Implementation of the latter helped to track the crystallization process to minimize the risk of cocrystn. of undesired isomer 4R,5S-7. In addition to this study using 1-(3-(Methylsulfonyl)propyl)piperazine dihydrochloride, there are many other studies that have used 1-(3-(Methylsulfonyl)propyl)piperazine dihydrochloride(cas: 939983-66-1Name: 1-(3-(Methylsulfonyl)propyl)piperazine dihydrochloride) was used in this study.

1-(3-(Methylsulfonyl)propyl)piperazine dihydrochloride(cas: 939983-66-1) is a member of sulfones.The sulfones, like the sulfonamides, are structural analogs of para-aminobenzoic acid that interfere with folic acid metabolism by acting as competitive inhibitors of dihydropteroate synthetase. All sulfones of clinical value are derivatives of dapsone, the most widely used member of this class.Name: 1-(3-(Methylsulfonyl)propyl)piperazine dihydrochloride

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

《Synthesis, characterization and carbonic anhydrase I and II inhibitory evaluation of new sulfonamide derivatives bearing dithiocarbamate》 was published in European Journal of Medicinal Chemistry in 2020. These research results belong to Saglik, Begum Nurpelin; Osmaniye, Derya; Cevik, Ulviye Acar; Levent, Serkan; Cavusoglu, Betul Kaya; Buyukemir, Oya; Nezir, Deniz; Karaduman, Abdullah Burak; Ozkay, Yusuf; Koparal, Ali Savas; Beydemir, Sukru; Kaplancikli, Zafer Asim. Quality Control of 1-Methylpiperazine The article mentions the following:

In this study, novel dithiocarbamate-sulfonamide derivatives I [R = Me, cyclohexyl, 4-O2NC6H4, etc.] were synthesized to investigate their inhibitory activity on purified human carbonic anhydrase (hCA) I and II. The IC50 and Ki values of the compounds were calculated to compare their inhibition profiles on hCA I and II isoenzymes. Acetazolamide was used as the standard inhibitor in the enzyme inhibition assay. Compounds I [R = Me, 4-MeC6H4CH2, CH2CH2NMe2, CH2CH2CH2NMe2, 2-pyridinyl, 2-pyrimidinyl] showed notable inhibitory effects against hCA I and II. Among these compounds, compound I [R = CH2CH2CH2NMe2] was found to be the most active derivate against both the hCA I and II enzymes with Ki values of 0.032 ± 0.001μM and 0.013 ± 0.0005μM, resp. The cytotoxicity of compounds I [R = Me, 4-MeC6H4CH2, CH2CH2NMe2, CH2CH2CH2NMe2, 2-pyridinyl, 2-pyrimidinyl] toward NIH/3T3 (mouse embryonic fibroblast cell line) was observed and the compounds were found to be non-cytotoxic. Furthermore, mol. docking studies were performed to investigate the interaction types between compound I [R = CH2CH2CH2NMe2] and the hCA I and II enzymes. As a result of this study a novel and potent class of CA inhibitors with good activity potential were identified. The experimental part of the paper was very detailed, including the reaction process of 1-Methylpiperazine(cas: 109-01-3Quality Control of 1-Methylpiperazine)

1-Methylpiperazine(cas: 109-01-3) can be used as mimic template in the preparation of molecularly imprinted microspheres (MIMs). It was also used to prepare the difunctional strong anion-exchange stationary phase from a 1,4-diazacyclohexane derivative..Quality Control of 1-Methylpiperazine

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

Rudolph, Dale A.; Alcazar, Jesus; Ameriks, Michael K.; Anton, Ana Belen; Ao, Hong; Bonaventure, Pascal; Carruthers, Nicholas I.; Chrovian, Christa C.; De Angelis, Meri; Lord, Brian; Rech, Jason C.; Wang, Qi; Bhattacharya, Anindya; Andres, Jose Ignacio; Letavic, Michael A. published their research in Bioorganic & Medicinal Chemistry Letters on August 15 ,2015. The article was titled 《Novel methyl substituted 1-(5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanones are P2X7 antagonists》.Application In Synthesis of (S)-tert-Butyl 2-methyl-3-oxopiperazine-1-carboxylate The article contains the following contents:

The optimization efforts that led to a novel series of Me substituted 1-(5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanones that are potent rat and human P2X7 antagonists are described. These efforts resulted in the discovery of compounds with good drug-like properties that are capable of high P2X7 receptor occupancy in rat following oral administration, including compounds I (P2X7 IC50 = 7.7 nM) and II (P2X7 IC50 = 7.7 nM). These compounds are expected to be useful tools for characterizing the effects of P2X7 antagonism in models of depression and epilepsy, and several of the compounds prepared are candidates for effective P2X7 PET tracers. The results came from multiple reactions, including the reaction of (S)-tert-Butyl 2-methyl-3-oxopiperazine-1-carboxylate(cas: 1799971-34-8Application In Synthesis of (S)-tert-Butyl 2-methyl-3-oxopiperazine-1-carboxylate)

(S)-tert-Butyl 2-methyl-3-oxopiperazine-1-carboxylate(cas: 1799971-34-8) belongs to piperazines. 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 In Synthesis of (S)-tert-Butyl 2-methyl-3-oxopiperazine-1-carboxylate

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

Evrard, Deborah A.; Zhou, Ping; Yi, Soo Y.; Zhou, Dahui; Smith, Deborah L.; Sullivan, Kelly M.; Hornby, Geoffrey A.; Schechter, Lee E.; Andree, Terrance H.; Mewshaw, Richard E. published an article on February 15 ,2005. The article was titled 《Studies towards the next generation of antidepressants. Part 4: Derivatives of 4-(5-fluoro-1H-indol-3-yl)cyclohexylamine with affinity for the serotonin transporter and the 5-HT1A receptor》, and you may find the article in Bioorganic & Medicinal Chemistry Letters.Application of 84807-09-0 The information in the text is summarized as follows:

Derivatives of the serotonin reuptake inhibitor 4-(5-fluoro-1H-indol-3-yl)cyclohexylamine, in which serotonin 1A (5-HT1A) receptor pharmacophoric elements are incorporated, are reported. Analogs exhibiting affinity for both the serotonin transporter and the 5-HT1A receptor are described. Compounds containing 1-(4-indolyl)piperazine and 2-(1H-indol-4-yloxy)ethylamine are promising leads for further SAR studies. In the experimental materials used by the author, we found 4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0Application of 84807-09-0)

4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0) belongs to piperazines. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines.Application of 84807-09-0

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

Synthetic Route of C5H14Cl2N2On October 20, 2015 ,《(2-Arylethenyl)-1,3,5-triazin-2-amines as a novel histamine H4 receptor ligands》 was published in European Journal of Medicinal Chemistry. The article was written by Kaminska, Katarzyna; Ziemba, Julia; Ner, Joanna; Schwed, Johannes Stephan; Lazewska, Dorota; Wiecek, Malgorzata; Karcz, Tadeusz; Olejarz, Agnieszka; Latacz, Gniewomir; Kuder, Kamil; Kottke, Tim; Zygmunt, Malgorzata; Sapa, Jacek; Karolak-Wojciechowska, Janina; Stark, Holger; Kiec-Kononowicz, Katarzyna. The article contains the following contents:

Within the constantly growing number of histamine H4 (H4R) receptor ligands there is a large group of azine derivatives A series of novel compounds in the group of 4-methylpiperazinyl-1,3,5-triazin-2-amines were designed and obtained. Structures were modified at the triazine 6-position by introduction of variously substituted arylethenyl moieties. Their affinities to histamine H4 receptors were evaluated in radioligand binding assays with use of Sf9 cells, transiently expressing human H4R. Pharmacol. studies identified 4-[(E)-2-(3-chlorophenyl)ethenyl]-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (Ki = 253 nM) as the most potent compound in the present series. In the experiment, the researchers used many compounds, for example, 1-Methylpiperazine dihydrochloride(cas: 34352-59-5Synthetic Route of C5H14Cl2N2)

1-Methylpiperazine dihydrochloride(cas: 34352-59-5) is used in the preparation of 2-(4-Methyl-1-piperazinylmethyl)acrylophenone(MPMAP), 1-methylpiperazine-1,4-diium tetrachloridozincate hemihydrate, 2-(4-Methyl-1-piperazinylmethyl)acrylophenone(MPMAP), an antimicrotubular drug..Synthetic Route of C5H14Cl2N2

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

《Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI》 was written by Marona-Lewicka, Danuta; Chemel, Benjamin R.; Nichols, David E.. Application In Synthesis of Abt-724 And the article was included in Psychopharmacology (Berlin, Germany) on April 30 ,2009. The article conveys some information:

Rationale: Lysergic acid diethylamide (LSD) differs from other types of hallucinogens in that it possesses direct dopaminergic effects. The exact nature of this component has not been elucidated. Objective: The present study sought to characterize the effects of several dopamine D4 agonists and antagonists on the discriminative stimulus effect of LSD at two pretreatment times and 2,5-dimethoxy-4-iodoamphetamine (DOI), a selective 5-HT2A/2C agonist. Materials and methods: Male Sprague-Dawley rats were trained in a two-lever, fixed ratio (FR) 50, food-reinforced task with LSD-30 (0.08 mg/kg, i.p., 30-min pretreatment time), LSD-90 (0.16 mg/kg, i.p., 90-min pretreatment time), and DOI (0.4 mg/kg, i.p., 30-min pretreatment time) as discriminative stimuli. Substitution and combination tests with the dopamine D4 agonists, ABT-724 and WAY 100635, were performed in all groups. Combination tests were run using the dopamine D4 antagonists A-381393 and L-745,870 and two antipsychotic drugs, clozapine and olanzapine. Results: WAY 100635 produced full substitution in LSD-90 rats, partial substitution in LSD-30 rats, and saline appropriate responding in DOI-trained rats. ABT-724 partially mimicked the LSD-90 and LSD-30 cues, but produced no substitution in DOI-trained rats. In combination tests, both agonists shifted the dose-response curve of LSD leftward, most potently for the LSD-90 cue. The D4 antagonists significantly attenuated both the LSD-90 and LSD-30 cue, but had no effect on the DOI cue. Conclusion: Dopamine D4 receptor activation plays a significant modulatory role in the discriminative stimulus effects in LSD-90-trained rats, most markedly for the later temporal phase of LSD, but has no effect on the cue produced by DOI.Abt-724(cas: 70006-24-5Application In Synthesis of Abt-724) was used in this study.

Abt-724(cas: 70006-24-5) belongs to piperazines. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines.Application In Synthesis of Abt-724

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

Onder, Ferah Comert; Sahin, Kader; Senturk, Murat; Durdagi, Serdar; Ay, Mehmet published an article in 2022. The article was titled 《Identifying highly effective coumarin-based novel cholinesterase inhibitors by in silico and in vitro studies》, and you may find the article in Journal of Molecular Graphics & Modelling.Computed Properties of C5H12N2 The information in the text is summarized as follows:

Inhibition of high cholinesterase levels including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), is one of the most important strategies for the treatment of Alzheime′s disease (AD). Clin. limited drugs are used in the treatment of AD, so there is a need to find new effective inhibitors today. Therefore, in this study, synthesized six coumarin carboxamides (A1, A2, B1-B4) were evaluated against AChE and BChE by combined in silico and in vitro studies. The in vitro assessment of studied compounds revealed that A1, A2, B3, and B4 showed highest inhibition potential against AChE and BChE. As demonstrated with our structure activity relationship (SAR) study, the promising inhibition result of AChE at nanomolar concentrations was obtained with heterocyclic amines including pyrrolidine and N-Me piperazine moieties for tertiary amide substituted coumarin compounds B3 and B4, displaying KI values of 9.78 nM and 8.07 nM, resp. Thus, compounds B3 and B4 had around 5.7- and 6.9-fold more potency compared to the reference mol., neostigmine. Moreover, coumarin-3-carboxamide derivative A1 bearing benzylmorpholine moiety on coumarin scaffold at position 3 displayed stronger inhibition potential against BChE. Furthermore, in order to better understand their mol. mechanisms in these targets, we conducted mol. docking and MD simulations. Our promising preclin. results show that the lead compounds A1, A2, B3 and B4 have high potential as effective inhibitors for the treatment of AD. The experimental process involved the reaction of 1-Methylpiperazine(cas: 109-01-3Computed Properties of C5H12N2)

1-Methylpiperazine(cas: 109-01-3) can be used as mimic template in the preparation of molecularly imprinted microspheres (MIMs). It was also used to prepare the difunctional strong anion-exchange stationary phase from a 1,4-diazacyclohexane derivative..Computed Properties of C5H12N2

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

Pullagurla, Manik; Siripurapu, Uma; Kolanos, Renata; Bondarev, Mikhail L.; Dukat, Malgorzata; Setola, V.; Roth, B. L.; Glennon, Richard A. published their research in Bioorganic & Medicinal Chemistry Letters on December 1 ,2005. The article was titled 《Binding of amine-substituted N 1-benzenesulfonylindoles at human 5-HT6 serotonin receptors》.Application In Synthesis of 4-(Piperazin-1-yl)-1H-indole The article contains the following contents:

An examination of several amine-substituted analogs of N1-benzenesulfonylindoles reveals that although they bind at human 5-HT6 serotonin receptors with high affinity, they are likely to bind in a dissimilar manner. The experimental part of the paper was very detailed, including the reaction process of 4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0Application In Synthesis of 4-(Piperazin-1-yl)-1H-indole)

4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0) belongs to piperazines. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines.Application In Synthesis of 4-(Piperazin-1-yl)-1H-indole

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

Safety of 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amineOn November 1, 2017 ,《Design, synthesis and biological evaluation of WZ4002 analogues as EGFR inhibitors》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Romu, Aireen A.; Lei, Zining; Zhou, Bin; Chen, Zhe-Sheng; Korlipara, Vijaya. The article conveys some information:

A series of thirty two anilinopyrimidines derived from WZ4002 has been synthesized and evaluated for percentage inhibition of six different EGFR kinases using LanthaScreen binding assay method (EGFR d746 – 750) or Z’LYTE assay method (EGFR-WT, EGFR d746 – 750, EGFR T790M, EGFR T790M L858R, EGFR C797S and EGFR T790M L858R C797S). Ortho-hydroxyacetamide I (R = 2′-NHCOCH2OH) exhibited complete inhibition of all the six kinases at 10 μM. Against the triple mutant, EGFR T790M C797S L858R, compounds I [R = 2′-NHCOCH2OCH2Ph, 2′-NHCOCH2OH, 2′-NHCO(CH2)2OCH2Ph, 2′-NHCO(CH2)2OH] exhibited complete inhibition at 10 μM and nearly complete inhibition at 1 μM. The target compounds were also evaluated using the MTT assay to determine their cytotoxic activity against human non-small cell lung cancer cells (PC9, PC9GR and H460) and mouse leukemic cells (Ba/F3 WT and Ba/F3T 3151). Overall, I [R = 2′-N3, 2′-NHCOCH2OCH2Ph, 2′-NHCOCH2OH, 2′-NHCO(CH2)2OCH2Ph, 2′-NHCO(CH2)2OH, 4′-NHCOCH2OCH2Ph, 4′-NHCOCH2OH] were found to be the most potent compounds across all five cell lines. In the experiment, the researchers used many compounds, for example, 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1Safety of 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine)

4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1) is a member of pyrimidine. Pyrimidine derivatives are an important class of N-heterocycles. They are well-known for their wide spectrum of promising biological activities such as antitumors, bactericidals, and fungicidal.Safety of 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine

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