Heterocyclic Building Blocks-piperazine

《Fragment-based modification of 2,4-diarylaminopyrimidine derivatives as ALK and ROS1 dual inhibitors to overcome secondary mutants》 was published in Bioorganic & Medicinal Chemistry in 2020. These research results belong to Zhu, Minglin; Li, Wei; Zhao, Tianming; Chen, Yuxiang; Li, Tong; Wei, Shangfei; Guo, Ming; Zhai, Xin. Related Products of 109-01-3 The article mentions the following:

The ALK and ROS1 dual inhibitors had capable of overcoming crizotinib-resistant mutants, two series of 2,4-diarylaminopyrimidine derivatives were designed, synthesized and evaluated for their in-vitro cytotoxic activity. The 2,4-diarylaminopyrimidine scaffold and derivatize the DAAP scaffold with sulfonyl and acrylamide moieties to extend the structure-activity relationship (SAR) study was retained. Some compounds exhibited excellent inhibitory activity with a double-digit nanomolar level in MTT assay. Four compounds were selected for enzymic assays further, the results led to the identification of a potent ALK and ROS1 dual inhibitor I [R = 4-ethylpiperazinyl], with IC50 values of 3.7 nM, 2.3 nM, 8.9 nM and 1.9 nM against ALK, ALKL1196M, ALKG1202R and ROS1, resp. Ultimately, the mol. docking studies on I [R = 4-ethylpiperazinyl] clearly disclosed reasonable and optimal binding interactions with ALK. In the experimental materials used by the author, we found 1-Methylpiperazine(cas: 109-01-3Related Products of 109-01-3)

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..Related Products of 109-01-3

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

In 2022,Ashworth, Ian W.; Frodsham, Lianne; Moore, Peter; Ronson, Thomas O. published an article in Journal of Organic Chemistry. The title of the article was 《Evidence of Rate Limiting Proton Transfer in an SNAr Aminolysis in Acetonitrile under Synthetically Relevant Conditions》.Application In Synthesis of 1-Methylpiperazine The author mentioned the following in the article:

An early synthetic step in the synthesis of adavosertib, AZD1775, is the SNAr reaction between 4-fluoronitrobenzene and 1-methylpiperazine in acetonitrile. A simple kinetics-based design of four reaction profiling experiments was used to investigate the kinetics of the reaction for the purpose of building a kinetic model. Fitting of the reaction profile data from two experiments conducted at 70°C with a different excess of 1-methylpiperazine showed the reaction to follow a third-order rate law with a second-order dependence upon 1-methylpiperazine. This was rationalized in terms of the reaction following a rate-limiting proton transfer mechanism (base catalyzed) in which the progress to product is driven by a proton transfer involving a second mol. of 1-methylpiperazine. The exptl. determined entropy of activation of -180 J K-1 is consistent with this mechanism. The formation of a low level impurity was found to be due to the presence of traces of piperazine in the 1-methylpiperazine, which was shown to react approx. 15 times faster than 1-methylpiperazine at 70°C. The rate constants for the 1-methylpiperazine catalyzed reaction of piperazine, 1-methylpiperazine, and the piperazine derived impurity were found to correlate in a Bronsted type anal. with the pKa’s (acetonitrile) of the amine nucleophile. In the experiment, the researchers used 1-Methylpiperazine(cas: 109-01-3Application In Synthesis 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..Application In Synthesis of 1-Methylpiperazine

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

Application In Synthesis of 1-MethylpiperazineIn 2020 ,《Design, synthesis, molecular docking and antiproliferative activity of some novel benzothiazole derivatives targeting EGFR/HER2 and TS》 was published in Bioorganic Chemistry. The article was written by Abdellatif, Khaled R. A.; Belal, Amany; El-Saadi, Mohamed T.; Amin, Noha H.; Said, Eman G.; Hemeda, Loah R.. The article contains the following contents:

A new series of benzothiazoles hybridized with a pyrimidine moiety, e.g., I (R = Cl), was designed and synthesized using the lead compound II (R1 = Ph). Various chem. modifications on the pyrimidine ring of II (R1 = Ph) at four different positions were done in a trial to get new multi-targeted anticancer agents. The structures of the newly synthesized compounds were established by their elemental analyses and spectral data. All final synthesized derivatives were submitted to the National Cancer Institute (NCI), USA, to be screened for their in vitro anticancer activity. Further evaluation for the cytotoxic activity of the most active compounds was performed using the MTT assay method. Compounds I [R = (4-acetylphenyl)amino, morpholin-4-yl, 4-methylpiperazin-1-yl], II (R1 = 4-oxo-4H-chromen-3-yl), and III were then selected for examination of their in vitro inhibitory activities against EGFR, HER2 and TS enzymes using lapatinib and 5FU as standards Furthermore, cell cycle anal. and apoptosis induction detection were also evaluated. Finally, mol. docking studies were carried out for compounds I [R = (4-acetylphenyl)amino, morpholin-4-yl, 4-methylpiperazin-1-yl], II (R1 = 4-oxo-4H-chromen-3-yl), and III to interpret their observed enzymic activities based on the ligand-protein interactions. The results came from multiple reactions, including the reaction of 1-Methylpiperazine(cas: 109-01-3Application In Synthesis 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..Application In Synthesis of 1-Methylpiperazine

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

Naylor, Alan; Judd, Duncan B.; Lloyd, Jane E.; Scopes, David I. C.; Hayes, Ann G.; Birch, Philip J. published an article in Journal of Medicinal Chemistry. The title of the article was 《A potent new class of κ-receptor agonist: 4-substituted 1-(arylacetyl)-2-[(dialkylamino)methyl]piperazines》.Application In Synthesis of (4-Benzylpiperazin-2-yl)methanol The author mentioned the following in the article:

The synthesis of 4-substituted 1-(arylacetyl)-2-[(alkylamino)methyl]piperazines I [R = CO2Me, R1 = R2 = Me; R = CO2Me, R1R2 = CH2CH:CHCH2CH2; R = COR3, R1R2 = (CH2)4, R3 = H, Me, Et, Pr, CH2OMe, CH:CH2, Ph, PhCH2; R = CO2R4, R1R2 = (CH2)4, R4 = Me, Et, Pr, Ph, PhCH2] and II [X = CHOH, CO, C:CHCO2Me-(E), -(Z)] and their activities as κ-opioid receptor agonists are described. This includes a range of 4-acyl and 4-carboalkoxy derivatives with the latter series showing the greatest κ-agonist activity. In particular, Me 4-[3,4-dichlorophenyl)acetyl]-3-[(1-pyrrolidinyl)methyl]-1-piperazinecarboxylate [I; R = CO2Me; R1R2 = (CH2)4] displays exceptional potency and selectivity. It showed the following activities in functional in vitro assays: rabbit vas deferens (κ-specific tissue) IC50 = 0.041 nM, rat vas deferens (μ-specific tissue) IC50 > 10 000 nM, and hamster vas deferens (δ-specific tissue) IC50 > 10 000 nM. Compound I [R = CO2Me; R1R2 = (CH2)4] is also a highly potent antinociceptive agent, as determined in the mouse acetylcholine-induced abdominal constriction test: ED50 = 0.000 52 mg/kg, s.c. The activity of I resides solely in its 3(R)-enantiomer. The κ-agonist activity in both the 4-acyl and the 4-carbamate series is sensitive to the size of the 4-substituent. In addition, it would appear that an appreciable neg. electrostatic potential in this region of the mol. is an important requirement for optimal potency.(4-Benzylpiperazin-2-yl)methanol(cas: 85817-34-1Application In Synthesis of (4-Benzylpiperazin-2-yl)methanol) was used in this study.

(4-Benzylpiperazin-2-yl)methanol(cas: 85817-34-1) 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 (4-Benzylpiperazin-2-yl)methanol

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

Raja Sekhara Reddy, B.; Pratap Reddy Gajulapalli, V.; Madhu Rekha, Estharla; Siva Krishna, Vagolu; Sriram, Dharmarajan; Sudakar Babu, K.; Kim, Eunha published an article on January 31 ,2022. The article was titled 《Design, synthesis, and in vitro biological evaluation of dehydroaripiprazole derivatives as antituberculosis agents and molecular docking study》, and you may find the article in Results in Chemistry.Recommanded Product: 34352-59-5 The information in the text is summarized as follows:

In this study, we describe the synthesis of novel piperazine-substituted 7-(4-chlorobutoxy) quinolin-2(1H) derivatives 5a-z, which were designed through specific structural modifications of aripiprazole. Furthermore, the synthesized derivatives were described as potent in vitro inhibitors of Mycobacterium tuberculosis (MTB) H37Rv strain growth. Among these compounds, 5c, 5 h, and 5r were found to be the most active ones with a MIC of 0.78 μg/mL. This activity is better compared to that of ethambutol (MIC = 1.56 μg/mL). These compounds failed to inhibit normal RAW 264.7 macrophages. Moreover, in vitro findings were supported by mol. docking studies with the known anti-TB target (InhA). The mol. docking studies on 5c, 5 h, and 5r hit compounds clearly validated hydrogen bonds interactions with the Enoyl-acp reductase (INHA). Therefore, these results indicate that this class of compounds may provide candidates for future development, and hopefully provide drug alternatives for tuberculosis treatment. In the experimental materials used by the author, we found 1-Methylpiperazine dihydrochloride(cas: 34352-59-5Recommanded Product: 34352-59-5)

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..Recommanded Product: 34352-59-5

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

Zhao, Yujun; Aguilar, Angelo; Bernard, Denzil; Wang, Shaomeng published an article on February 12 ,2015. The article was titled 《Small-Molecule Inhibitors of the MDM2-p53 Protein-Protein Interaction (MDM2 Inhibitors) in Clinical Trials for Cancer Treatment》, and you may find the article in Journal of Medicinal Chemistry.Name: 1-(3-(Methylsulfonyl)propyl)piperazine dihydrochloride The information in the text is summarized as follows:

A review. Design of small-mol. inhibitors (MDM2 inhibitors) to block the MDM2-p53 protein-protein interaction has been pursued as a new cancer therapeutic strategy. In recent years, potent, selective, and efficacious MDM2 inhibitors have been successfully obtained and seven such compounds have been advanced into early phase clin. trials for the treatment of human cancers. Here, we review the design, synthesis, properties, preclin., and clin. studies of these clin.-stage MDM2 inhibitors. In the part of experimental materials, we found many familiar compounds, such as 1-(3-(Methylsulfonyl)propyl)piperazine dihydrochloride(cas: 939983-66-1Name: 1-(3-(Methylsulfonyl)propyl)piperazine dihydrochloride)

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 and structure-activity relationships for tetrahydroisoquinoline-based inhibitors of Mycobacterium tuberculosis》 was written by Lu, Guo-Liang; Tong, Amy S. T.; Conole, Daniel; Sutherland, Hamish S.; Choi, Peter J.; Franzblau, Scott G.; Upton, Anna M.; Lotlikar, Manisha U.; Cooper, Christopher B.; Denny, William A.; Palmer, Brian D.. COA of Formula: C5H12N2 And the article was included in Bioorganic & Medicinal Chemistry in 2020. The article conveys some information:

A series of 5,8-disubstituted tetrahydroisoquinolines e.g., 2-((5-(4-chlorophenyl)pyridin-2-yl)methyl)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydroisoquinoline were shown to be effective inhibitors of M. tb in culture and modest inhibitors of M. tb ATP synthase. There was a broad general trend of improved potency with higher lipophilicity. Large substituents (e.g., Bn) at the tetrahydroquinoline 5-position were well-tolerated, while N-methylpiperazine was the preferred 8-substituent. Structure-activity relationships for 7-linked side chains showed that the nature of the 7-linking group was important; -CO- and -COCH2- linkers were less effective than -CH2- or -CONH- ones. This suggests that the positioning of a terminal aromatic ring is important for target binding. Selected compounds showed much faster rates of microsomal clearance than the clin. ATP synthase inhibitor bedaquiline, and modest inhibition of mycobacterial ATP synthase. The experimental part of the paper was very detailed, including the reaction process of 1-Methylpiperazine(cas: 109-01-3COA of Formula: 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..COA of Formula: C5H12N2

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

《An exit beyond the pharmacophore model for 5-HT6R agents – a new strategy to gain dual 5-HT6/5-HT2A action for triazine derivatives with procognitive potential》 was written by Kucwaj-Brysz, Katarzyna; Ali, Wesam; Kurczab, Rafal; Sudol-Talaj, Sylwia; Wilczynska-Zawal, Natalia; Jastrzebska-Wiesek, Magdalena; Satala, Grzegorz; Mordyl, Barbara; Zeslawska, Ewa; Agnieszka-Olejarz-Maciej; Czarnota, Kinga; Latacz, Gniewomir; Partyka, Anna; Wesolowska, Anna; Nitek, Wojciech; Handzlik, Jadwiga. Quality Control of 1-Methylpiperazine dihydrochloride And the article was included in Bioorganic Chemistry on April 30 ,2022. The article conveys some information:

Herein, the first highly potent 5-HT6/5-HT2A receptor (5-HT6/5-HT2AR) dual antagonists in a group of 1,3,5-triazine compounds have been discovered as a result of an exit beyond the hydrophobic feature of the pharmacophore model for 5-HT6R antagonists. Design and synthesis of the series I (X = O, S; R1 = 4-PhOC6H4, 4-PhC6H4, 2-naphthyl, 1-naphthyl; R2 = H, Me, Et, n-Bu, R3 = H; R2 = R3 = Me) of ether and thioether derivatives of 1,3,5-triazines with the double-ring aromatic region have been performed. The new compounds I were examined within the comprehensive pharmacol. screening, including: radioligand binding assays, functional and ADMET studies in vitro as well as behavioral tests in rats. Crystallog. aspects and computer-aided structure-activity relationship were analyzed as well. This comprehensive approach led to selection of the compound I [X = S; R1 = 2-naphthyl; R2 = R3 = Me; (II)] with the most significant dual 5-HT6/5-HT2AR antagonistic action (5-HT6R Ki = 11 nM, 5-HT2AR Ki = 39 nM). Moreover, the compound II has satisfactory ADMETox properties in vitro, i.e.: the high permeability through biol. membranes, high metabolic stability, neither mutagenic nor hepatotoxic effects and moderate ability to inhibit CYP3A4. Above all, the compound II showed ability to reverse the pharmacol.-induced (MK-801) memory impairment at low doses (1-3 mg/kg) in Novel Object Recognition (NOR) test in rats. These results indicate a promising potency of dual 5-HT6/5-HT2AR antagonism in the search for novel strategy to fight Alzheimer’s disease, which remains an unmet clin. need. In the experiment, the researchers used 1-Methylpiperazine dihydrochloride(cas: 34352-59-5Quality Control of 1-Methylpiperazine dihydrochloride)

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..Quality Control of 1-Methylpiperazine dihydrochloride

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

Synthetic Route of C5H11ClN2O2SOn March 11, 2013, Moukha-chafiq, Omar; Reynolds, Robert C. published an article in ACS Combinatorial Science. The article was 《Parallel Solution-Phase Synthesis of an Adenosine Antibiotic Analog Library》. The article mentions the following:

A library of eighty one adenosine antibiotic analogs was prepared under the Pilot Scale Library Program of the NIH Roadmap initiative from 5′-amino-5′-deoxy-2′,3′-O-isopropylidene-adenosine (I). Diverse aldehyde, sulfonyl chloride and carboxylic acid reactant sets were condensed to I, in solution-phase fashion, leading after acid-mediated hydrolysis to the targeted compounds in good yields and high purity. No marked antituberculosis or anticancer activity was noted on preliminary cellular testing, but these nucleoside analogs should be useful candidates for other types of biol. activity.4-Methyl-1-piperazinesulfonyl Chloride(cas: 1688-95-5Synthetic Route of C5H11ClN2O2S) was used in this study.

4-Methyl-1-piperazinesulfonyl Chloride(cas: 1688-95-5) is a member of sulfamide. Sulfamide was used in the synthesis of: Schiff bases of the type ArCH=NSO2NH2; 1H,3H-2,1,3-benzothiadiazin-4-one-2,2-dioxide (BTDD); sulfamide analogs of oleoylethanolamide analogs in a study of PPARα activation.Synthetic Route of C5H11ClN2O2S

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

Cheng, Chuanjie; Sun, Jianwei; Xing, Lixin; Xu, Jimin; Wang, Xinyan; Hu, Yuefei published their research in Journal of Organic Chemistry on August 7 ,2009. The article was titled 《Highly Chemoselective Pd-C Catalytic Hydrodechlorination Leading to the Highly Efficient N-Debenzylation of Benzylamines》.Application of 34352-59-5 The article contains the following contents:

In the presence of 1,1,2-trichloroethane, a novel procedure for the Pd-C catalytic N-debenzylation of benzylamines was established. The method proceeded in a synergistic catalytic system and directly gave the products as crystalline amine hydrochlorides in practically quant. yields. In the experiment, the researchers used many compounds, for example, 1-Methylpiperazine dihydrochloride(cas: 34352-59-5Application of 34352-59-5)

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..Application of 34352-59-5

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