Category: piperazines

A Phase I Pharmacokinetic and Pharmacodynamic Study of TKI258, an Oral, Multitargeted Receptor Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors was written by Sarker, Debashis;Molife, Rhoda;Evans, T. R. Jeffrey;Hardie, Maryon;Marriott, Cheryl;Butzberger-Zimmerli, Priska;Morrison, Rosemary;Fox, Judith A.;Heise, Carla;Louie, Sharianne;Aziz, Natasha;Garzon, Felix;Michelson, Glenn;Judson, Ian R.;Jadayel, Dalal;Braendle, Edgar;de Bono, Johann S.. And the article was included in Clinical Cancer Research in 2008.Formula: C24H27FN6O4 This article mentions the following:

To determine the maximum tolerated dose (MTD) dose-limiting toxicity, and pharmacokinetic and pharmacodynamic profile of TKI258 (formerly CHIR-258). A phase I dose escalating trial in patients with advanced solid tumors was performed. Treatment was initially as single daily doses on an intermittent 7-day on/7-day off schedule. Following a protocol amendment, a second schedule comprised, during cycle 1, 7-day on/7-day off treatment followed by 14 days of continuous daily dosing; subsequent cycles comprised 28 days of daily dosing. Pharmacokinetics and evaluation of phosphorylated extracellular signal-regulated kinase (ERK) in peripheral blood mononuclear cells were done during the first 28 days of each schedule. Thirty-five patients were treated in four intermittent (25-100 mg/d) and three continuous (100-175 mg/d) dosing cohorts. Observed drug-related toxicities were nausea and vomiting, fatigue, headache, anorexia, and diarrhea. Dose-limiting toxicities were grade 3 hypertension in one patient at 100 mg continuous dosing, grade 3 anorexia in a second patient at 175 mg, and grade 3 alk. phosphatase elevation in a third patient at 175 mg. One patient had a partial response (melanoma) and two patients had stable disease >6 mo. TKI258 pharmacokinetics were linear over the dose range of 25 to 175 mg. Five of 14 evaluable patients had modulation of phosphorylated ERK levels. The MTD was defined as 125 mg/d. Evidence of antitumor activity in melanoma and gastrointestinal stromal tumors warrants further investigation, and other phase I studies are ongoing. Further pharmacodynamic evaluation is required in these studies to evaluate the biol. effects of TKI258. In the experiment, the researchers used many compounds, for example, 4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7Formula: C24H27FN6O4).

4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. 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.Formula: C24H27FN6O4

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

Design, Synthesis and Screening Studies of Potent Thiazol-2-Amine Derivatives as Fibroblast Growth Factor Receptor 1 Inhibitors was written by Suneel Kumar, B. V. S.;Lakshmi, Narasu;Kumar, M. Ravi;Rambabu, Gundla;Manjashetty, Thimmappa H.;Arunasree, Kalle M.;Sriram, Dharmarajan;Ramkumar, Kavya;Neamati, Nouri;Dayam, Raveendra;Sarma, J. A. R. P.. And the article was included in Current Topics in Medicinal Chemistry (Sharjah, United Arab Emirates) in 2014.Formula: C24H27FN6O4 This article mentions the following:

Fibroblast growth factor receptor 1 (FGFR1) a tyrosine kinase receptor, plays important roles in angiogenesis, embryonic development, cell proliferation, cell differentiation, and wound healing. The FGFR isoforms and their receptors (FGFRs) considered as a potential targets and under intense research to design potential anticancer agents. Fibroblast growth factors (FGF’s) and its growth factor receptors (FGFR) plays vital role in one of the critical pathway in monitoring angiogenesis. In the current study, quant. pharmacophore models were generated and validated using known FGFR1 inhibitors. The pharmacophore models were generated using a set of 28 compounds (training). The top pharmacophore model was selected and validated using a set of 126 compounds (test set) and also using external validation. The validated pharmacophore was considered as a virtual screening query to screen a database of 400,000 virtual mols. and pharmacophore model retrieved 2800 hits. The retrieved hits were subsequently filtered based on the fit value. The selected hits were subjected for docking studies to observe the binding modes of the retrieved hits and also to reduce the false positives. One of the potential hits (thiazole-2-amine derivative) was selected based the pharmacophore fit value, dock score, and synthetic feasibility. A few analogs of the thiazole-2-amine derivative were synthesized. These compounds were screened for FGFR1 activity and anti-proliferative studies. The top active compound showed 56.87% inhibition of FGFR1 activity at 50 渭M and also showed good cellular activity. Further optimization of thiazole-2-amine derivatives is in progress. In the experiment, the researchers used many compounds, for example, 4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7Formula: C24H27FN6O4).

4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7) 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. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Formula: C24H27FN6O4

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

A simple and efficient synthesis of the antimigraine drug lomerizine was written by Narsaiah, A. Venkat;Kumar, J. Kranthi. And the article was included in Synthesis in 2010.SDS of cas: 27469-60-9 This article mentions the following:

The synthesis of the antimigraine drug 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine was carried out in very good yields. The 5-step synthesis started from bis(4-fluorophenyl)methanone. This route can be applied for large-scale preparation of lomerizine. In the experiment, the researchers used many compounds, for example, 4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9SDS of cas: 27469-60-9).

4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.SDS of cas: 27469-60-9

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

Prevalence, Antimicrobial Susceptibility and Resistance Gene Detection in Bacteria Isolated from Goldfish and Tiger Barb from Ornamental Fish Farms of Tamil Nadu was written by Hemamalini, Nallaiah;Shanmugam, Seerappalli Aran;Kathirvelpandian, Ayyathurai;Deepak, Agarwal;Kaliyamurthi, Venkatachalam;Suresh, Eswaran;Ezhilmathi, Selvaram. And the article was included in Indian Journal of Microbiology in 2022.Application of 62893-19-0 This article mentions the following:

This study aims to determine the antimicrobial resistance (AMR) pattern in freshwater ornamental cyprinids, such as Goldfish and Tiger barb. Mol. characterization of bacterial isolates confirmed the presence of 7 bacterial isolates in Goldfish and 6 in Tiger barb. Antimicrobial susceptibility test using 36 antibiotics revealed a higher resistance pattern for bacitracin, rifampicin, trimethoprim, cefalexin, ampicillin, amoxicillin, nalidixic acid and nitrofurantoin. Sulphafurazole, norfloxacin and ciprofloxacin were effective against all the bacterial isolates derived from Goldfish and Tiger barb. Most bacterial isolates exhibited > 0.2 multi-drug resistance index (MDR), indicating the severity of antibiotic use in the culture system. The finding of the present study suggests that ornamental fish may act as the reservoir of MDR bacteria and dissemination of resistance genes to clin. and human commensal bacteria through horizontal gene transfer. In the experiment, the researchers used many compounds, for example, (6R,7R)-7-((R)-2-(4-Ethyl-2,3-dioxopiperazine-1-carboxamido)-2-(4-hydroxyphenyl)acetamido)-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (cas: 62893-19-0Application of 62893-19-0).

(6R,7R)-7-((R)-2-(4-Ethyl-2,3-dioxopiperazine-1-carboxamido)-2-(4-hydroxyphenyl)acetamido)-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (cas: 62893-19-0) 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. Application of 62893-19-0

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

Effect of transient blockade of N-methyl-D-aspartate receptors at neonatal stage on stress-induced lactate metabolism in the medial prefrontal cortex of adult rats: Role of 5-HT1A receptor agonism was written by Uehara, Takashi;Itoh, Hiroko;Matsuoka, Tadasu;Rujescu, Dan;Genius, Just;Seo, Tomonori;Sumiyoshi, Tomiki. And the article was included in Synapse (Hoboken, NJ, United States) in 2012.Quality Control of 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 This article mentions the following:

Decreased activity of the medial prefrontal cortex (mPFC) has been considered a basis for core symptoms of schizophrenia, an illness associated with a neurodevelopmental origin. Evidence from preclin. and clin. studies indicates that serotonin (5-HT)1A receptors play a crucial role in the energy metabolism of the mPFC. This study was undertaken to determine (1) if transient blockade of N-methyl-D-aspartate receptors during the neonatal stage inhibit energy demands in response to stress, as measured by extracellular lactate concentrations, in the mPFC at the young adult stage, and (2) if tandospirone, a 5-HT1A partial agonist, reverses the effect of the neonatal insult on energy metabolism Male pups received MK-801 (0.20 mg/kg) on postnatal days (PDs) 7-10. On PD 63, footshock stress-induced lactate levels were measured using in vivo microdialysis technique. Tandospirone (0.1, 1.0, and 5.0 mg/kg) was administered once daily for 14 days before the measurement of lactate levels. Neonatal MK-801 treatment suppressed footshock stress-induced lactate production in the mPFC, but not caudate-putamen, whereas basal lactate levels were not significantly changed in either brain region. The MK-801-induced suppression of footshock stress-induced lactate production in the mPFC was attenuated by tandospirone at 1.0mg/kg/day, but not 0.1 or 5.0 mg/kg/day, which is an effect antagonized by coadministration of WAY-100635, a selective 5-HT1A antagonist. These results suggest a role for impaired lactate metabolism in some of the core symptoms of schizophrenia, for example, neg. symptoms and cognitive deficits. The implications for the ability of 5-HT1A agonism to ameliorate impaired lactate production in the mPFC of this animal model are discussed. Synapse, 2012. 漏 2011 Wiley Periodicals, Inc. 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: 112457-95-1Quality Control of 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).

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. 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.Quality Control of 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

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

Dual specificity phosphatase (DUSP)-4 is induced by platelet-derived growth factor -BB in an Erk1/2-, STAT3- and p53-dependent manner was written by Yin, Runting;Eger, Glenda;Sarri, Niki;Rorsman, Charlotte;Heldin, Carl-Henrik;Lennartsson, Johan. And the article was included in Biochemical and Biophysical Research Communications in 2019.Computed Properties of C30H30Cl2N4O4 This article mentions the following:

Dual specificity phosphatase (DUSP) 4 has been described as a neg. regulator of MAP kinase signaling, in particular for the ERK1/2 and JNK pathways. We found that DUSP4 expression was upregulated in response to prolonged platelet-derived growth factor (PDGF)-BB stimulation. The PDGF-BB-induced DUSP4 expression was dependent on ERK1/2, STAT3 and p53. We found that inhibition of ERK1/2 effectively reduced DUSP4 mRNA levels, whereas STAT3 was necessary for maintaining p53 expression. P53 has binding sites in the DUSP4 promoter and was found to promote DUSP4 expression. In the experiment, the researchers used many compounds, for example, 4-(cis-4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one (cas: 548472-68-0Computed Properties of C30H30Cl2N4O4).

4-(cis-4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one (cas: 548472-68-0) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Computed Properties of C30H30Cl2N4O4

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

Design, synthesis and antitubercular evaluation of novel series of N-[4-(piperazin-1-yl)phenyl]cinnamamide derivatives was written by Patel, Kavitkumar N.;Telvekar, Vikas N.. And the article was included in European Journal of Medicinal Chemistry in 2014.Formula: C15H20FN3O4 This article mentions the following:

The analogs of N-[4-(piperazin-1-yl)phenyl]cinnamamide were designed and synthesized by a mol. hybridization approach in which part C of the designed mol. was linked through amide and carbamate functionality that improves the physicochem. properties and govern the pharmacokinetic and pharmacodynamic behavior. The systematic modification was done around the Part C to explore the structure activity relationship of antitubercular cinnamamides. All 52 compounds were evaluated for antitubercular activity against Mycobacterium tuberculosis (M. tb) using Resazurin microtitre plate assay (REMA). Compound I with trifluoromethyl substitution exhibited good antitubercular activity of 3.125 渭g/mL. The synthesized N-[4-(piperazin-1-yl)phenyl]cinnamamide derivatives showed promising activity against M. tb. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate (cas: 154590-34-8Formula: C15H20FN3O4).

tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate (cas: 154590-34-8) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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: C15H20FN3O4

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

Substrate profiling of Finegoldia magna SufA protease, inhibitor screening and application to prevent human fibrinogen degradation and bacteria growth in vitro was written by Burchacka, Ewa;Sienczyk, Marcin;Frick, Inga-Maria;Wysocka, Magdalena;Lesner, Adam;Oleksyszyn, Jozef. And the article was included in Biochimie in 2014.Product Details of 27913-99-1 This article mentions the following:

SufA, which belongs to the subtilisin-like serine protease family, contains a non-canonical Asp-His-Ser catalytic triad. Under in vitro conditions, SufA is capable of human fibrinogen hydrolysis leading to inhibition of fibrin network formation, thus suggesting its important role in the development and progression of Finegoldia magna infections. In addition, it has been demonstrated that SufA can hydrolyze antibacterial peptides such as LL-37 and the chemokine MIG/CXCL 9, hence evading host defense mechanisms. Although the SufA protease from F. magna was discovered several years ago, its optimal substrate preference has not yet been identified. Considering the role of SufA, we have focused on the profiling of its substrate sequence preference spanning S1-S3 binding pockets using the FRET (fluorescence resonance energy transfer) approach. Next, based on the structure of the P1 residue of the developed substrate, we narrowed the inhibitor screening to the phosphonic analogs of amino acids containing an arginine-like side chain. Among all the compounds tested, only Cbz-6-AmNphth^P(OPh)₂ showed any inhibitory activity against SufA displaying k₂/K_i value of 10 800 M^-1 s^-1. In addition, it prevented SufA-mediated human fibrinogen hydrolysis in vitro and exhibited potent antibacterial activity against F. magna, Staphylococcus aureus and Escherichia coli.Herein, we report on the substrate specificity, synthesis and kinetic evaluation of phosphonic inhibitors of SufA protease from F. magna which could help to establish its function in pathogenesis development and may lead to the elaboration of new antibacterial drugs. In the experiment, the researchers used many compounds, for example, 4-(4-Methylpiperazin-1-yl)benzaldehyde (cas: 27913-99-1Product Details of 27913-99-1).

4-(4-Methylpiperazin-1-yl)benzaldehyde (cas: 27913-99-1) 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.Product Details of 27913-99-1

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

Overall survival in patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer treated with a cyclin-dependent kinase 4/6 inhibitor plus fulvestrant: a US Food and Drug Administration pooled analysis was written by Gao, Jennifer J.;Cheng, Joyce;Prowell, Tatiana M.;Bloomquist, Erik;Tang, Shenghui;Wedam, Suparna B.;Royce, Melanie;Krol, Danielle;Osgood, Christy;Ison, Gwynn;Sridhara, Rajeshwari;Pazdur, Richard;Beaver, Julia A.;Amiri-Kordestani, Laleh. And the article was included in Lancet Oncology in 2021.COA of Formula: C23H30N8O This article mentions the following:

Cyclin-dependent kinase 4/6 inhibitors (CDKIs) are oral targeted agents approved for use in combination with endocrine therapy as first-line or second-line treatment of patients with hormone receptor-pos., HER2-neg., advanced or metastatic breast cancer. We previously reported the pooled analyses of progression-free survival in patients in specific clinicopathol. subgroups, all of whom received consistent benefit from the addition of a CDKI to hormonal therapy. Here, we report the pooled overall survival results in patients treated with a CDKI and fulvestrant. In this exploratory anal., we pooled individual patient data from three phase 3 randomised trials of CDKI or placebo in combination with fulvestrant in patients with breast cancer submitted to the US Food and Drug Administration and approved before Aug 1, 2020, in support of marketing applications. All analyzed patients were aged at least 18 years, had an Eastern Cooperative Oncol. Group performance status of 0-1, had hormone receptor-pos., HER2-neg. advanced or metastatic breast cancer, and received at least one dose of CDKI or placebo in combination with fulvestrant. The median overall survival was estimated using Kaplan-Meier methods, and hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression models. Patients were analyzed collectively, by number of previous lines of systemic endocrine therapy in any disease setting (first-line or endocrine naive vs second-line and later), and in various clinicopathol. subgroups of interest. The estimated median overall survival was not reported by group when the pooled population included patients treated across lines of therapy because of potential patient heterogeneity. All results presented are considered exploratory and hypothesis generating. Across the three pooled trials, 1960 patients were randomly assigned between Oct 7, 2013, and June 10, 2016 (12 patients were not treated and 1296 [66%] patients were randomly assigned to CDKI and 652 [33%] to placebo). In all treated patients (n = 1948), the estimated HR for overall survival was 0路77 (95% CI 0路68-0路88), with a median follow-up of 43路7 mo (IQR 37路 8-47路7) and deaths in 935 (48%) of the 1948 patients. The difference in estimated median overall survival was 7路 1 mo, favoring CDKIs. In patients who received CDKIs or placebo in combination with fulvestrant as first-line systemic endocrine therapy (two trials; n=396), the estimated HR for overall survival was 0路74 (95% CI 0路52-1路07), with a median follow-up of 39路4 mo (IQR 37路0-42路2). 123 (31%) of these patients died. The difference in estimated median overall survival could not be calculated because median overall survival was not estimable (95% CI 50路9-not estimable) in the CDKI group and was 45路7 mo (95% CI 41路7-not estimable) in the placebo group. In patients who received CDKIs or placebo in combination with fulvestrant as second-line or later systemic endocrine therapy (three trials; n=1552), the estimated HR for overall survival was 0路77 (95% CI 0路67-0路89), with a median follow-up of 45路1 mo (95% CI 39路2-48路5). 812 (52%) of these patients died. The difference in estimated median overall survival was 7路0 mo, favoring CDKIs. The addition of CDKIs to fulvestrant resulted in a consistent overall survival benefit in all pooled patients and within most clinicopathol. subgroups of interest. These findings support the existing standard of care of CDKIs plus fulvestrant for the treatment of patients with hormone receptor-pos., HER2-neg., advanced breast cancer.None. 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. Simple N-substituted piperazines have been found in many drug molecules. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.COA of Formula: C23H30N8O

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

Discovery of 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amines as potent, selective and orally bioavailable LRRK2 inhibitors was written by Ding, Xiao;Stasi, Luigi Piero;Ho, Ming-Hsun;Zhao, Baowei;Wang, Hailong;Long, Kai;Xu, Qiongfeng;Sang, Yingxia;Sun, Changhui;Hu, Huan;Yu, Haihua;Wan, Zehong;Wang, Lizhen;Edge, Colin;Liu, Qian;Li, Yi;Dong, Kelly;Guan, Xiaoming;Tattersall, F. David;Reith, Alastair D.;Ren, Feng. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2018.Product Details of 93643-24-4 This article mentions the following:

Inhibition of LRRK2 kinase activity with small mols. has emerged as a potential novel therapeutic treatment for Parkinson’s disease. Herein the authors disclose the discovery of a 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine series as potent LRRK2 inhibitors identified through a kinase-focused set screening. Optimization of the physicochem. properties and kinase selectivity led to the discovery of compound 7 ((4-((4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone), which exhibited potent in vitro inhibition of LRRK2 kinase activity, good physicochem. properties and kinase selectivity across the kinome. Moreover, compound 7 was able to penetrate into the CNS, and in vivo pharmacol. studies revealed significant inhibition of Ser 935 phosphorylation in the brain of both rats (30 and 100 mg/kg) and mice (45 mg/kg) following oral administration. In the experiment, the researchers used many compounds, for example, (S)-1,4-Diazabicyclo[4.3.0]nonane (cas: 93643-24-4Product Details of 93643-24-4).

(S)-1,4-Diazabicyclo[4.3.0]nonane (cas: 93643-24-4) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. 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.Product Details of 93643-24-4

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