Month: October 2022

HPLC of Formula: 109-01-3In 2022 ,《Structural and PK-guided identification of indole-based non-acidic autotaxin (ATX) inhibitors exhibiting high in vivo anti-fibrosis efficacy in rodent model》 was published in European Journal of Medicinal Chemistry. The article was written by Lei, Hongrui; Cao, Zhi; Wu, Huinan; Li, Tong; Wang, Xinyu; Chen, Yuxiang; Ma, Enlong; Sun, Lixin; Zhai, Xin. The article contains the following contents:

In recent decades, pharmacol. targeting of the autotaxin (ATX)/lysophosphatidic acid (LPA) axis accounted for excellent disease management benefits. Herein, to extend the scope of structure-activity relationships (SARs), fifteen indole-based carbamate derivatives I [R = 4-Me, 3,4-difluoro, 2,3-dichloro; R1 = pyrrolidin-1-yl, (4-methyl-1-piperidyl), (4-methylpiperazin-1-yl); R2 = H, CH3, etc] were prepared to evaluate the ATX inhibitory potency. Among them, compound I [R = 3,5-dichloro; R1 = morpholino; R2 = H] bearing morpholine moiety was identified as the optimal ATX inhibitor (0.41 nM), superior to the pos. control GLPG1690 (2.90 nM). To resolve the intractable issue of poor pharmacokinetic (PK) property, urea moiety was introduced as a surrogate of carbamate which furnished compounds II [R3 = morpholino, (4-hydroxy-1-piperidyl), [2-(hydroxymethyl)pyrrolidin-1-yl]; R4 = H, 4-Cl, 4-F, etc]. The dedicated modification identified the diethanolamine entity II [R3 = [bis(2-hydroxyethyl)amino]; R4 = (3-chloro-4-methoxy-phenyl)] with satisfactory water solubility and PK profiles with a min. sacrifice of ATX inhibition (2.17 nM). The most promising candidate II [R3 = [bis(2-hydroxyethyl)amino]; R4 = (3-chloro-4-methoxy-phenyl)] was evaluated for anti-fibrosis effect in a bleomycin challenged mice lung fibrosis model. Upon treatment with II [R3 = [bis(2-hydroxyethyl)amino]; R4 = (3-chloro-4-methoxy-phenyl)], the in vivo ATX activity in both lung homogenate and broncheoalveolar fluid (BALF) sample was significantly down-regulated. Furthermore, the gene expression of pro-fibrotic cytokines transforming growth factor-β (TGF-β), interleukin- 6 (IL-6) and tumor necrosis factor-α (TNF-α) in lung tissue was reduced to normal level. Collectively, the promising biol. effects may advocate potential application of II [R3 = [bis(2-hydroxyethyl)amino]; R4 = (3-chloro-4-methoxy-phenyl)] in fibrosis relevant diseases. In the part of experimental materials, we found many familiar compounds, such as 1-Methylpiperazine(cas: 109-01-3HPLC of Formula: 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..HPLC of Formula: 109-01-3

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

Category: piperazinesIn 2022 ,《Design and synthesis of novel quinazolinone derivatives as anti-HBV agents with TLR8 agonist effect》 appeared in European Journal of Medicinal Chemistry. The author of the article were Qiu, Jingying; Zhou, Qingqing; Zou, Yueting; Li, Shuqiong; Yang, Lihua; Chen, Wang; Gao, Jian; Gu, Xiaoke. The article conveys some information:

In this work, a series of novel quinazolinone derivatives I [R1 = benzyl, 2-furylmethyl, 2-thienylmethyl, etc.; R2 = H, 2-MeO, 3-F, etc.; R3 = (4-methylpiperazin-1-yl), (4-hydroxy-1-piperidyl), (2-aminopyrimidin-4-yl)oxy, etc.] were synthesized and evaluated as novel anti-HBV agents. Among them, compound I [R1 = 2-furylmethyl; R2 = 2-MeO; R3 = (2-aminopyrimidin-4-yl)oxy] exhibited potent inhibitory effect on HBV DNA replication in both wild type and drug resistant (lamivudine and entecavir) HBV strains with IC50 values of 0.15 and 0.10μM, resp. Notably, the selective index value of I [R1 = 2-furylmethyl; R2 = 2-MeO; R3 = (2-aminopyrimidin-4-yl)oxy] was high above 66.67, indicating the favorable safety profile. Mol. docking study indicated that compound I [R1 = 2-furylmethyl; R2 = 2-MeO; R3 = (2-aminopyrimidin-4-yl)oxy] well fitted into the binding pocket of TLR8 protein-protein interface. Dual-luciferase reporter gene assay further confirmed that compound I [R1 = 2-furylmethyl; R2 = 2-MeO; R3 = (2-aminopyrimidin-4-yl)oxy] could dose-dependently activate TLR8, thus effectively inducing the activity of TLR8-dependent NF-κB. Collectively, compound I [R1 = 2-furylmethyl; R2 = 2-MeO; R3 = (2-aminopyrimidin-4-yl)oxy] displayed potent anti-HBV activities and TLR8 agonist effect in vitro, and might be a potential immunomodulatory anti-HBV agent to warrant further investigation. In the part of experimental materials, we found many familiar compounds, such as 1-Methylpiperazine(cas: 109-01-3Category: piperazines)

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..Category: piperazines

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

《2,5-Disubstituted pyridines as potent GPR119 agonists》 was written by Wu, Yulin; Kuntz, Judith D.; Carpenter, Andrew J.; Fang, Jing; Sauls, Howard R.; Gomez, Daniel J.; Ammala, Carina; Xu, Yun; Hart, Shane; Tadepalli, Sarva. Electric Literature of C7H16N2O2S And the article was included in Bioorganic & Medicinal Chemistry Letters on April 15 ,2010. The article conveys some information:

A series of 2-piperazinyl-5-alkoxypyridines were synthesized and screened against human GPR119 receptor. Through SAR anal., compounds containing 2-alkylsulfonylpiperazinyl-5-alkoxypyridines were discovered and found to be potent agonists of the human GPR119 receptor. The experimental process involved the reaction of 1-(Isopropylsulfonyl)piperazine(cas: 534615-34-4Electric Literature of C7H16N2O2S)

1-(Isopropylsulfonyl)piperazine(cas: 534615-34-4) 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.Electric Literature of C7H16N2O2S

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

《Synthesis and evaluation of 2-anilinopyrimidines bearing 3-aminopropamides as potential epidermal growth factor receptor inhibitors》 was written by Han, Chun; Wan, Ledong; Ji, Hongbin; Ding, Ke; Huang, Zhangjian; Lai, Yisheng; Peng, Sixun; Zhang, Yihua. Quality Control of 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine And the article was included in European Journal of Medicinal Chemistry on April 22 ,2014. The article conveys some information:

Novel compounds were synthesized and biol. evaluated. Several ones exhibited stronger inhibitory activity than gefitinib against EGFR L858R/T790M and antiproliferative effects on H1975 and HCC827 cells. The 3-aminopropamide in some compoundslike compound I could be converted to the active acrylamide in the presence of arginine. Importantly, compound I showed improved stability relative to compound WZ4002 whose structure is same to I excepting an acrylamide moiety. Interestingly, compound II, a NO donating compound of I, showed more potent and selective inhibition than compound I on H1975 cells. Significantly, compound II produced high levels of NO in H1975 cells but not in non-tumorous 16HBE cells, and its inhibition was diminished by NO scavenger. Furthermore, compound II dose-dependently produced inhibitory effects on EGFR downstream signaling in H1975 cells. In the experiment, the researchers used 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1Quality Control 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.Quality Control 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

Product Details of 34352-59-5On October 25, 2012 ,《Optimization of Imidazo[4,5-b]pyridine-Based Kinase Inhibitors: Identification of a Dual FLT3/Aurora Kinase Inhibitor as an Orally Bioavailable Preclinical Development Candidate for the Treatment of Acute Myeloid Leukemia》 was published in Journal of Medicinal Chemistry. The article was written by Bavetsias, Vassilios; Crumpler, Simon; Sun, Chongbo; Avery, Sian; Atrash, Butrus; Faisal, Amir; Moore, Andrew S.; Kosmopoulou, Magda; Brown, Nathan; Sheldrake, Peter W.; Bush, Katherine; Henley, Alan; Box, Gary; Valenti, Melanie; Brandon, Alexis de Haven; Raynaud, Florence I.; Workman, Paul; Eccles, Suzanne A.; Bayliss, Richard; Linardopoulos, Spiros; Blagg, Julian. The article contains the following contents:

Optimization of the imidazo[4,5-b]pyridine-based series of Aurora kinase inhibitors led to the identification of 6-chloro-7-(4-(4-chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine (I), a potent inhibitor of Aurora kinases (Aurora-A Kd = 7.5 nM, Aurora-B Kd = 48 nM), FLT3 kinase (Kd = 6.2 nM), and FLT3 mutants including FLT3-ITD (Kd = 38 nM) and FLT3(D835Y) (Kd = 14 nM). FLT3-ITD causes constitutive FLT3 kinase activation and is detected in 20-35% of adults and 15% of children with acute myeloid leukemia (AML), conferring a poor prognosis in both age groups. In an in vivo setting, I strongly inhibited the growth of a FLT3-ITD-pos. AML human tumor xenograft (MV4-11) following oral administration, with in vivo biomarker modulation and plasma free drug exposures consistent with dual FLT3 and Aurora kinase inhibition. Compound I, an orally bioavailable dual FLT3 and Aurora kinase inhibitor, was selected as a preclin. development candidate for the treatment of human malignancies, in particular AML, in adults and children.1-Methylpiperazine dihydrochloride(cas: 34352-59-5Product Details of 34352-59-5) was used in this study.

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..Product Details of 34352-59-5

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

Application of 84807-09-0On May 9, 2013 ,《Biophysical Fragment Screening of the β1-Adrenergic Receptor: Identification of High Affinity Arylpiperazine Leads Using Structure-Based Drug Design》 appeared in Journal of Medicinal Chemistry. The author of the article were Christopher, John A.; Brown, Jason; Dore, Andrew S.; Errey, James C.; Koglin, Markus; Marshall, Fiona H.; Myszka, David G.; Rich, Rebecca L.; Tate, Christopher G.; Tehan, Benjamin; Warne, Tony; Congreve, Miles. The article conveys some information:

Biophys. fragment screening of a thermostabilized β1-adrenergic receptor (β1AR) using surface plasmon resonance (SPR) enabled the identification of moderate affinity, high ligand efficiency (LE) arylpiperazine hits 7 and 8. Subsequent hit to lead follow-up confirmed the activity of the chemotype, and a structure-based design approach using protein-ligand crystal structures of the β1AR resulted in the identification of several fragments that bound with higher affinity, including indole 19 and quinoline 20. In the first example of GPCR crystallog. with ligands derived from fragment screening, structures of the stabilized β1AR complexed with 19 and 20 were determined at resolutions of 2.8 and 2.7 Å, resp. After reading the article, we found that the author used 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

Name: 4-(Piperazin-1-yl)-1H-indoleOn May 9, 2013 ,《Structure-Based Fragment Screening Is Demonstrated To Be a Practical Lead Discovery Method for a Representative G-Protein-Coupled Receptor》 appeared in Journal of Medicinal Chemistry. The author of the article were Stevens, Benjamin D.. The article conveys some information:

A review. In this paper the author discusses the work of Christopher et al. who described a successful approach leading to the discovery of structurally novel β1 adrenoreceptor ligands driven exclusively by biophys. methods. A work that highlights the promise of such technol. for utilization in future GPCR lead discovery programs andprovides an appealing alternative to traditional approaches forreceptors where structural stabilization is possible. The experimental part of the paper was very detailed, including the reaction process of 4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0Name: 4-(Piperazin-1-yl)-1H-indole)

4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0) 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: 4-(Piperazin-1-yl)-1H-indole

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

Scapecchi, Serena; Martini, Elisabetta; Manetti, Dina; Ghelardini, Carla; Martelli, Cecilia; Dei, Silvia; Galeotti, Nicoletta; Guandalini, Luca; Romanelli, Maria Novella; Teodori, Elisabetta published an article in Bioorganic & Medicinal Chemistry. The title of the article was 《Structure-activity relationship studies on unifiram (DM232) and sunifiram (DM235), two novel and potent cognition enhancing drugs》.Safety of 1-(Isopropylsulfonyl)piperazine The author mentioned the following in the article:

Structure-activity relationships on two novel potent cognition enhancing drugs, unifiram and sunifiram, are reported. Although none of the compounds synthesized reached the potency of the parent drugs, some fairly active compounds have been identified that may represent new leads to develop other cognition enhancing drugs. An interesting result of this research is the identification of two compounds that are endowed with amnesing activity (the opposite of the activity of the original mols.) and are nearly equipotent to scopolamine. Moreover, two other compounds of the series were found endowed with analgesic activity on a rat model of neuropathic pain at the dose of 1 mg/kg. In the experimental materials used by the author, we found 1-(Isopropylsulfonyl)piperazine(cas: 534615-34-4Safety of 1-(Isopropylsulfonyl)piperazine)

1-(Isopropylsulfonyl)piperazine(cas: 534615-34-4) 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.Safety of 1-(Isopropylsulfonyl)piperazine

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

The author of 《Synthesis, crystal structure, vibrational, optical properties, and a theoretical study of a new Pb(II) complex with bis(1-methylpiperazine-1,4-diium): [C5H14N2]2PbCl6·3H2O》 were Mrad, Mohamed Lahbib; Belhajsalah, Souhir; Abdelbaky, Mohammed Said M.; Garcia-Granda, Sergio; Essalah, Khaled; Ben Nasr, C.. And the article was published in Journal of Coordination Chemistry in 2019. Name: 1-Methylpiperazine The author mentioned the following in the article:

A study of the solid-state x-ray structure of the new organic-inorganic compound [C5H14N2]2PbCl6·3H2O shows a layered organization of the (PbCl6)4- anions, with (R2NH2)+ groups and water mols. developed in the [001] plane at x = (2n + 1)/4. The crystal structure is stabilized by N – H···Cl, N – H···O, O – H···Cl, O – H···O, and C – H···Cl hydrogen bonds. The powder x-ray diffraction and X-ray photoelectron spectroscopic (XPS) analyses confirm the phase purity of the crystal sample. The intermol. contacts are quantified using the Hirshfeld surfaces computational method. The major inter-contacts contributing to the Hirshfeld surfaces are H…Cl, H…H, and O…H. The vibrational modes were identified and assigned by IR and Raman spectroscopies. The optical properties were studied by UV-visible and photoluminescence spectroscopic studies. The compound was characterized by thermal anal. to determine its thermal behavior with respect to the temperature Finally, XPS anal. is reported for analyzing the surface chem. of [C5H14N2]2PbCl6·3H2O. In the experiment, the researchers used 1-Methylpiperazine(cas: 109-01-3Name: 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..Name: 1-Methylpiperazine

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

Zhang, Xiangyu; Huang, Hailan; Zhang, Ziheng; Yan, Jiangkun; Wu, Tianxiao; Yin, Wenbo; Sun, Yixiang; Wang, Xinran; Gu, Yanting; Zhao, Dongmei; Cheng, Maosheng published their research in European Journal of Medicinal Chemistry in 2021. The article was titled 《Design, synthesis and biological evaluation of novel benzofuran derivatives as potent LSD1 inhibitors》.HPLC of Formula: 109-01-3 The article contains the following contents:

A series of benzofurans I [R = 3-aminopropylamino, pyrrolidin-3-ylamino, piperazin-1-yl, etc.; Ar = pyrimidin-5-yl, p-tolyl, 1-methylindazol-5-yl, etc.] were designed, synthesized and biochem. evaluated as LSD1 inhibitors based on scaffold hopping and conformational restriction strategy. Most of the compounds I potently suppressed the enzymic activities of LSD1 and potently inhibited tumor cells proliferation. In particular, the representative compound I [R = (3S)-3-amino-1-piperidyl; Ar = p-tolyl] exhibited excellent LSD1 inhibition at the mol. levels with IC50 = 0.065μM, as well as anti-proliferation against MCF-7, MGC-803, H460, A549 and THP-1 tumor cells with IC50 values of 2.90 ± 0.32, 5.85 ± 0.35, 2.06 ± 0.27, 5.74 ± 1.03 and 6.15 ± 0.49μM, resp. The binding modes of these compounds I were rationalized by mol. docking. Meanwhile, a preliminary druggability evaluation showed that compound I [R = (3S)-3-amino-1-piperidyl; Ar = p-tolyl] displayed favorable liver microsomal stability and weak inhibitory activity against CYPs at 10μM. Remarkably, H460 xenograft tumors studies revealed that compound I [R = (3S)-3-amino-1-piperidyl; Ar = p-tolyl] demonstrated robust in-vivo antitumor efficacy without significant side effects. All the results demonstrated that compound I [R = (3S)-3-amino-1-piperidyl; Ar = p-tolyl] could represent a promising lead for further development. In the experimental materials used by the author, we found 1-Methylpiperazine(cas: 109-01-3HPLC of Formula: 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..HPLC of Formula: 109-01-3

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