Tag: M.W=150-200

Guo, Ming published the artcileDual potent ALK and ROS1 inhibitors combating drug-resistant mutants: Synthesis and biological evaluation of aminopyridine-containing diarylaminopyrimidine derivatives, Formula: C10H16N4, the publication is European Journal of Medicinal Chemistry (2018), 322-333, database is CAplus and MEDLINE.

To identify ALK and ROS1 dual inhibitors conferring resistance to ALK secondary mutations, especially ‘gatekeeper’ L1196 M and the most predominant ceritinib-resistant G1202R mutations, a series of novel 2,4-diarylaminopyrimidine analogs were designed and synthesized by incorporating 2-alkoxy-6-alicyclic aminopyridinyl motifs. The biol. evaluations on cellular and enzymic assays led to identification of compound F-1, which turned out to be effective against ALKWT, ROS1WT, ALKL1196M and ALKG1202R kinases with IC50 of 2.1 nM, 2.3 nM, 1.3 nM and 3.9 nM, resp., superior to crizotinib and ceritinib. Moreover, F-1 exhibited significant cytotoxicity on ALK-addicted Karpas299, H2228, and Ba/F3 cell expressing G1202R mutant, as well as ROS1-pos. HCC78 cell with IC50 values ranging from 10 nM to 43 nM. Notably, F-1 was capable of suppressing phospho-ALK and its relative downstream signaling pathways, and eventually, inducing cell apoptosis in a dose-dependent manner in Karpas-299 cell. Together, F-1 is validated as a promising ALK/ROS1 dual inhibitor great potential for G1202R ALK mutation cancers.

European Journal of Medicinal Chemistry published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C10H16N4, Formula: C10H16N4.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Li, Xiang published the artcileSynthesis, Biological Evaluation, and Molecular Docking Studies of Xanthone Sulfonamides as ACAT Inhibitors, Safety of 1-(3-Cyanophenyl)piperazine, the publication is Chemical Biology & Drug Design (2015), 85(3), 394-403, database is CAplus and MEDLINE.

Three series of xanthone sulfonamides were synthesized, and their inhibitory activities against acyl-Co-A: cholesterol acyltransferase (ACAT) were evaluated. Results showed that most of the title compounds exhibited strong inhibitory activity against ACAT, and several compounds were proved to be more active than the pos. control Sandoz 58-035. Computational docking experiments indicated that the interaction between inhibitors and ACAT contained the H-bond interaction, the hydrophobic interaction, and the narrow hydrophobic cleft.

Chemical Biology & Drug Design published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Safety of 1-(3-Cyanophenyl)piperazine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Yang, Shyh-Ming published the artcileDiscovery of NCT-501, a Potent and Selective Theophylline-Based Inhibitor of Aldehyde Dehydrogenase 1A1 (ALDH1A1), Category: piperazines, the publication is Journal of Medicinal Chemistry (2015), 58(15), 5967-5978, database is CAplus and MEDLINE.

Aldehyde dehydrogenases (ALDHs) metabolize reactive aldehydes and possess important physiol. and toxicol. functions in areas such as CNS, metabolic disorders, and cancers. Increased ALDH (e.g., ALDH1A1) gene expression and catalytic activity are vital biomarkers in a number of malignancies and cancer stem cells, highlighting the need for the identification and development of small mol. ALDH inhibitors. A new series of theophylline-based analogs as potent ALDH1A1 inhibitors is described. The optimization of hits identified from a quant. high throughput screening (qHTS) campaign led to analogs with improved potency and early ADME properties. This chemotype exhibits highly selective inhibition against ALDH1A1 over ALDH3A1, ALDH1B1, and ALDH2 isoenzymes as well as other dehydrogenases such as HPGD and HSD17β4. Moreover, the pharmacokinetic evaluation of selected analog (NCT-501) is also highlighted.

Journal of Medicinal Chemistry published new progress about 71260-16-7. 71260-16-7 belongs to piperazines, auxiliary class Piperazine, name is 2-Methyl-1-(piperazin-1-yl)propan-1-one, and the molecular formula is C12H10FeO4, Category: piperazines.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Xu, Feng published the artcileSynthesis, antitumor evaluation and molecular docking studies of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives, COA of Formula: C8H16N2O, the publication is Bioorganic & Medicinal Chemistry Letters (2016), 26(13), 3042-3047, database is CAplus and MEDLINE.

A series of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives were synthesized and evaluated for their antitumor activities. These compounds exhibited potent antiproliferative activities against MCF-7, Bewo and HL-60 cells and c-Met kinase inhibitory activities. Three compounds were highly effective against MCF-7, Bewo and HL-60 cells with IC₅₀ values in 1.09-2.24 μM. Mol. docking was further performed to study the inhibitor-c-Met kinase interactions, and compound 4-([1,2,4]Triazolo[4,3-b][1,2,4,5]tetrazin-3-yl)morpholine was potently bound to the c-Met kinase with three hydrogen bonds. The further research on acute toxicity and in vivo antitumor activity of compound 4-([1,2,4]Triazolo[4,3-b][1,2,4,5]tetrazin-3-yl)morpholine to ICR (Institute of Cancer Research) mice were carried out, and found 4-([1,2,4]Triazolo[4,3-b][1,2,4,5]tetrazin-3-yl)morpholine with a certain toxicity but good efficacy in vivo. Based on the preliminary results, compound 4-([1,2,4]Triazolo[4,3-b][1,2,4,5]tetrazin-3-yl)morpholine with potent c-Met kinase inhibitory activity may be a potential anticancer agent.

Bioorganic & Medicinal Chemistry Letters published new progress about 71260-16-7. 71260-16-7 belongs to piperazines, auxiliary class Piperazine, name is 2-Methyl-1-(piperazin-1-yl)propan-1-one, and the molecular formula is C25H23NO4, COA of Formula: C8H16N2O.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Chen, Xing published the artcileDiscovery and In Vivo Anti-inflammatory Activity Evaluation of a Novel Non-peptidyl Non-covalent Cathepsin C Inhibitor, Application of 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, the publication is Journal of Medicinal Chemistry (2021), 64(16), 11857-11885, database is CAplus and MEDLINE.

Cathepsin C (Cat C) participates in inflammation and immune regulation by affecting the activation of neutrophil serine proteases (NSPs). Therefore, cathepsin C is an attractive target for treatment of NSP-related inflammatory diseases. Here, the complete discovery process of the first potent “non-peptidyl non-covalent cathepsin C inhibitor” was described with hit finding, structure optimization, and lead discovery. Starting with hit 14, structure-based optimization and structure-activity relationship study were comprehensively carried out, and lead compound 54 was discovered as a potent drug-like cathepsin C inhibitor both in vivo and in vitro. Also, compound 54 (with cathepsin C Enz IC₅₀ = 57.4 nM) exhibited effective anti-inflammatory activity in an animal model of chronic obstructive pulmonary disease. These results confirmed that the non-peptidyl and non-covalent derivative could be used as an effective cathepsin C inhibitor and encouraged us to continue further drug discovery on the basis of this finding.

Journal of Medicinal Chemistry published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C10H16N4, Application of 6-(4-Methylpiperazin-1-yl)pyridin-3-amine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Tang, Haifeng published the artcileDesign and synthesis of a new class of malonyl-CoA decarboxylase inhibitors with anti-obesity and anti-diabetic activities, COA of Formula: C11H13N3, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(20), 6088-6092, database is CAplus and MEDLINE.

A new series of thiazole-substituted 1,1,1,3,3,3-hexafluoro-2-propanols, e.g. I, were prepared and evaluated as malonyl-CoA decarboxylase (MCD) inhibitors. Key analogs caused dose-dependent decreases in food intake and body weight in obese mice. Acute treatment with these compounds also led to a drop in elevated blood glucose in a murine model of type II diabetes.

Bioorganic & Medicinal Chemistry Letters published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C19H14Cl2, COA of Formula: C11H13N3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Guo, Jing published the artcileDiscovery of novel TrkA allosteric inhibitors: Structure-based virtual screening, biological evaluation and preliminary SAR studies, Related Products of piperazines, the publication is European Journal of Medicinal Chemistry (2022), 114022, database is CAplus and MEDLINE.

Tropomyosin receptor kinases A (TrkA) is a potential therapeutic target for the treatment of numerous tumor types and chronic pain. However, most of the reported TrkA inhibitors are ATP competitive pan-Trks inhibitors that lack subtype selectivity. A selective TrkA inhibitor may provide valuable therapeutic benefits. Here, we described the discovery of novel TrkA allosteric inhibitors by structure-based virtual screening. A promising hit (I, TrkA cell IC₅₀ = 3.32 μM) was selected for further studies. The binding free energy between TrkA and I was calculated In addition, the preliminary structure-activity relationship (SAR) studies with I were investigated. The results suggest that I can be used as a starting point for development of TrkA allosteric inhibitors.

European Journal of Medicinal Chemistry published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C10H16N4, Related Products of piperazines.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Zhao, Hong-Yi published the artcileDiscovery of Potent PROTACs Targeting EGFR Mutants through the Optimization of Covalent EGFR Ligands, Name: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, the publication is Journal of Medicinal Chemistry (2022), 65(6), 4709-4726, database is CAplus and MEDLINE.

To overcome the intractable problem of drug resistance, proteolysis targeting chimeras (PROTACs) targeting EGFR mutants were developed by optimizing covalent EGFR ligands. Covalent or reversible covalent pyrimidine- or purine-containing PROTACs were designed, synthesized, and evaluated. As a consequence, covalent PROTAC I, with a novel purine-containing EGFR ligand, was discovered as a highly potent degrader against EGFR^L858R/T790M and EGFR^del19, reaching the lowest DC₅₀ values among all reported EGFR-targeting PROTACs. Furthermore, I exhibited excellent cellular activity against the H1975 and HCC827 cell lines with high selectivity. Mechanism investigation indicated that the lysosome was involved in the degradation process. Importantly, the covalent binding strategy was proven to be an effective approach for the design of PROTACs targeting EGFR^L858R/T790M, which laid the practical foundation for further development of potent EGFR-targeting PROTACs.

Journal of Medicinal Chemistry published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C12H16BBrO2, Name: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Richard, David J. published the artcileIncorporation of water-solubilizing groups in pyrazolopyrimidine mTOR inhibitors: Discovery of highly potent and selective analogs with improved human microsomal stability, Recommanded Product: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, the publication is Bioorganic & Medicinal Chemistry Letters (2009), 19(24), 6830-6835, database is CAplus and MEDLINE.

A series of highly potent and selective pyrazolopyrimidine mTOR inhibitors which contain water-solubilizing groups attached to the 6-arylureidophenyl moiety have been prepared Such derivatives displayed superior potency to those in which these appendages were attached to alternative sites. In comparison to unfunctionalized arylureido compounds, these analogs, particularly, I, demonstrated enhanced cellular potency and significantly improved stability towards human microsomes, resulting in an mTOR inhibitor with impressive efficacy in a xenograft model with an intermittent dosing regimen.

Bioorganic & Medicinal Chemistry Letters published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C10H16N4, Recommanded Product: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Chen, Peng-Jen published the artcileDesign, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D₃ receptor ligands, Safety of 1-(3-Cyanophenyl)piperazine, the publication is Bioorganic & Medicinal Chemistry Letters (2019), 29(18), 2690-2694, database is CAplus and MEDLINE.

As part of our on-going effort to explore the role of dopamine receptors in drug addiction and identify potential novel therapies for this condition, we have a identified a series of N-(4-(4-Ph piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide D₃ ligands. Members of this class are highly selective for D₃ vs. D₂, and we have identified two compounds (13g and 13r) whose rat in vivo IV pharmacokinetic properties that indicate that they are suitable for assessment in in vivo efficacy models of substance use disorders.

Bioorganic & Medicinal Chemistry Letters published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Safety of 1-(3-Cyanophenyl)piperazine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics