Tag: M.W=200-250

Yuan, Xinrui published the artcileDesign, synthesis and biological evaluation of pyridone-aminal derivatives as MNK1/2 inhibitors, Quality Control of 73874-95-0, the main research area is pyridone aminal derivative preparation MNK1 MNK2 inhibitor colon cancer; MNK1/2; Pyridone–aminal; eFT508; eIF4E.

Excessive phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) plays a major role in the dysregulation of mRNA translation and the activation of tumor cell signaling. eIF4E is exclusively phosphorylated by mitogen-activated protein kinase interacting kinases 1 and 2 (MNK1/2) on Ser209. So, MNK1/2 inhibitors could decrease the level of p-eIF4E and regulate tumor-associated signaling pathways. A series of pyridone-aminal derivatives were synthesized and evaluated as MNK1/2 inhibitors. Several compounds exhibited great inhibitory activity against MNK1/2 and selected compounds showed moderate to excellent anti-proliferative potency against hematol. cancer cell lines. In particular, compound 42i (MNK1 IC50 = 7.0 nM; MNK2 IC50 = 6.1 nM) proved to be the most potent compound against TMD-8 cell line with IC50 value of 0.91 μM. Furthermore, 42i could block the phosphorylation level of eIF4E in CT-26 cell line, and 42i inhibited the tumor growth of CT-26 allograft model significantly. These results indicated that compound 42i was a promising MNK1/2 inhibitor for the potent treatment of colon cancer.

Bioorganic & Medicinal Chemistry published new progress about Antiproliferative agents. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Quality Control of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Wang, Xinran published the artcileDesign, synthesis and biological evaluation of 2-aminopyrimidine-based LSD1 inhibitors, HPLC of Formula: 73874-95-0, the main research area is human liver microsome cell proliferation LSD1 inhibitor; 2-Aminopyrimidine; LSD1 inhibitors; Molecular docking; Structure-activity relationships.

AZD9291, with excellent pharmaceutical properties, has been reported to have certain LSD1 inhibitory activity. Therefore, we carried out structural optimization based on the AZD9291 skeleton to increase the LSD1 inhibitory potential of the compound Then, a series of 2-aminopyrimidine derivatives were designed and synthesized as LSD1 inhibitors, and their structure-activity relationships were studied. The most promising compound, X43, with an IC50 of 0.89 μM showed remarkable LSD1 selectivity not only to EGFRwt (>100-fold) but also to MAO-A/B (>50-fold). Further studies showed that X43 inhibited LSD1 activity and induced the apoptosis of A549 cells in a dose-dependent manner. Meanwhile, compound X43 showed a superior ability to inhibit the proliferation of A549 and THP-1 cells, with IC50 values of 1.62 μM and 1.21 μM, resp. Then, analyses of the stability of human liver microsomes, CYP inhibition and in vivo pharmacokinetics in rats showed that X43 had favorable profiles in vitro and in vivo and the potential for further study. Our findings suggested that a 2-aminopyrimidine-based LSD1 inhibitor deserves further investigation as a treatment for LSD1-overexpressing cancer.

Bioorganic Chemistry published new progress about Antiproliferative agents. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, HPLC of Formula: 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Bu, Hong published the artcileDesign, synthesis and biological evaluation of imidazopyridazine derivatives containing isoquinoline group as potent MNK1/2 inhibitors, Product Details of C10H20N2O2, the main research area is eIF4E MNK inhibitor ETC 206; ETC-206; MNK1/2 kinases; MNKs inhibitor; eIF4E.

Mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are located at the meeting-point of ERK and p38 MAPK signaling pathways, which can phosphorylate eukaryotic translation initiation factor 4E (eIF4E) at the conserved serine 209 exclusively. MNKs modulate the translation of mRNA involved in tumor-associated signaling pathways. Consequently, selective inhibitors of MNK1/2 could reduce the level of phosphorylated eIF4E. Series of imidazopyrazines, imidazopyridazines and imidazopyridines derivatives were synthesized and evaluated as MNK1/2 inhibitors. Several compounds exhibited great inhibitory activity against MNK1/2 and selected compounds showed moderate to excellent anti-proliferative potency against diffuse large B-cell lymphoma (DLBCL) cell lines. In particular, compound II-5 (MNK1 IC50 = 2.3 nM; MNK2 IC50 = 3.4 nM) exhibited excellent enzymic inhibitory potency and proved to be the most potent compound against TMD-8 and DOHH-2 cell lines with IC50 value of 0.3896μM and 0.4092μM resp. These results demonstrated that compound II-5 could be considered as a potential MNK1/2 inhibitor for further investigation.

Bioorganic & Medicinal Chemistry published new progress about Antiproliferative agents. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Product Details of C10H20N2O2.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Motika, Stephen E. published the artcileGram-Negative Antibiotic Active Through Inhibition of an Essential Riboswitch, Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is antibiotic riboswitch ribocil.

Multidrug-resistant Gram-neg. (GN) infections for which there are few available treatment options are increasingly common. The development of new antibiotics for these pathogens is challenging because of the inability of most small mols. to accumulate inside GN bacteria. Using recently developed predictive guidelines for compound accumulation in Escherichia coli, we have converted the antibiotic Ribocil C, which targets the FMN (FMN) riboswitch, from a compound lacking whole-cell activity against wild-type GN pathogens into a compound that accumulates to a high level in E. coli, is effective against Gram-neg. clin. isolates, and has efficacy in mouse models of GN infections. This compound allows for the first assessment of the translational potential of FMN riboswitch binders against wild-type Gram-neg. bacteria.

Journal of the American Chemical Society published new progress about Acinetobacter baumannii. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Name: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Kamakolanu, Uma Gayathri published the artcileDiscovery and Structure-Activity Relationships of Nociceptin Receptor Partial Agonists That Afford Symptom Ablation in Parkinson’s Disease Models, SDS of cas: 73874-95-0, the main research area is piperdinylindole synthesis antiparkinson SAR nociceptin opioid receptor Parkinsons dyskinesia.

A novel series of C(3)-substituted piperdinylindoles were developed as nociceptin opioid receptor (NOP) partial agonists to explore a pharmacol. hypothesis that NOP partial agonists would afford a dual pharmacol. action of attenuating Parkinson’s disease (PD) motor symptoms and development of levodopa-induced dyskinesias. SAR around the C-3 substituents investigated effects on NOP binding, intrinsic activity, and selectivity and showed that while the C(3)-substituted indoles are selective, high affinity NOP ligands, the steric, polar, and cationic nature of the C-3 substituents affected intrinsic activity to afford partial agonists with a range of efficacies. Compounds 4, 5, and 9 with agonist efficacies between 25% and 35% significantly attenuated motor deficits in the 6-OHDA-hemilesioned rat model of PD. Further, unlike NOP antagonists, which appear to worsen dyskinesia expression, these NOP partial agonists did not attenuate or worsen dyskinesia expression. The NOP partial agonists and their SAR reported here may be useful to develop nondopaminergic treatments for PD.

Journal of Medicinal Chemistry published new progress about Antiparkinsonian agents. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, SDS of cas: 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Martinez-Gonzalez, Sonia published the artcileDiscovery of novel triazolo[4,3-b]pyridazin-3-yl-quinoline derivatives as PIM inhibitors, COA of Formula: C10H20N2O2, the main research area is triazolopyridazinylquinoline derivative PIM kinase inhibition antiproliferative anticancer; Anticancer agents; Antiproliferative activity; Chemical probes; PIM-1 inhibitors; Selective PIM-1/PIM-3 inhibitors; Synergistic effects; pan-PIM inhibitors.

PIM kinase family (PIM-1, PIM-2 and PIM-3) is an appealing target for the discovery and development of selective inhibitors, useful in various disease conditions in which these proteins are highly expressed, such as cancer. The significant effort put, in the recent years, towards the development of small mols. exhibiting inhibitory activity against this protein family has ended up with several mols. entering clin. trials. As part of our ongoing exploration for potential drug candidates that exhibit affinity towards this protein family, we have generated a novel chem. series of triazolo[4,3-b]pyridazine based tricycles by applying a scaffold hopping strategy over our previously reported potent pan-PIM inhibitor ETP-47453 (compound 2). The structure-activity relationship studies presented herein demonstrate a rather selective PIM-1/PIM-3 biochem. profile for this novel series of tricycles, although pan-PIM and PIM-1 inhibitors have also been identified. Selected examples show significant inhibition of the phosphorylation of BAD protein in a cell-based assay. Moreover, optimized and highly selective compounds, such as 42, did not show significant hERG inhibition at 20 μM concentration, and proved its antiproliferative activity and utility in combination with particular antitumoral agents in several tumor cell lines.

European Journal of Medicinal Chemistry published new progress about Acute myeloid leukemia. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, COA of Formula: C10H20N2O2.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Dolbois, Aymeric published the artcile1,4,9-Triazaspiro[5.5]undecan-2-one Derivatives as Potent and Selective METTL3 Inhibitors, HPLC of Formula: 73874-95-0, the main research area is prostate cancer AML anticancer METTL3 inhibitors optimization crystallog ADME.

N6-methyladenosine (m6A) is the most frequent of the 160 RNA modifications reported so far. Accumulating evidence suggests that the METTL3/METTL14 protein complex, part of the m6A regulation machinery, is a key player in a variety of diseases including several types of cancer, type 2 diabetes, and viral infections. Here we report on a protein crystallog.-based medicinal chem. optimization of a METTL3 hit compound that has resulted in a 1400-fold potency improvement (IC50 of 5 nM for the lead compound 22 (UZH2)(I) in a time-resolved Forster resonance energy transfer (TR-FRET) assay). The series has favorable ADME properties as physicochem. characteristics were taken into account during hit optimization. UZH2 shows target engagement in cells and is able to reduce the m6A/A level of polyadenylated RNA in MOLM-13 (acute myeloid leukemia) and PC-3 (prostate cancer) cell lines.

Journal of Medicinal Chemistry published new progress about Acute myeloid leukemia. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, HPLC of Formula: 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Kanouni, Toufike published the artcileDiscovery of CC-90011: A Potent and Selective Reversible Inhibitor of Lysine Specific Demethylase 1 (LSD1), Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is CC90011 inhibitor lysine specific demethylase 1 LSD1.

Histone demethylase LSDl (KDMlA) belongs to the FAD dependent family of monoamine oxidases and is vital in regulation of mammalian biol. Dysregulation and overexpression of LSD1 are hallmarks of a number of human diseases, particularly cancers that are characterized as morphol. poorly differentiated. As such, inhibitors of LSD1 have potential to be beneficial as a cancer therapy. The most clin. advanced inhibitors of LSDl are covalent inhibitors derived from tranylcypromine (TCP). Herein, we report the discovery of a novel series of reversible and selective LSDl inhibitors. Exploration of structure-activity relationships (SARs) and optimization of ADME properties resulted in the identification of clin. candidate CC-90011. CC-90011 exhibits potent on-target induction of cellular differentiation in acute myeloid leukemia (AML) and small cell lung cancer (SCLC) cell lines, and antitumor efficacy in patient-derived xenograft (PDX) SCLC models. CC-90011 is currently in phase 2 trials in patients with first line, extensive stage SCLC (ClinicalTrials.gov identifier: NCT03850067).

Journal of Medicinal Chemistry published new progress about Acute myeloid leukemia. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Name: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Zhang, Shengrui published the artcileMerocyanine-based turn-on fluorescent probe for the sensitive and selective determination of thiophenols via a pKa shift mechanism, Formula: C10H20N2O2, the main research area is merocyanine fluorescent probe thiophenol acid dissociation constant shift mechanism; Fluorescent probe; Merocyanine; Thiophenol; pK(a) shift.

The development of fluorescent probes for the sensitive and selective determination of highly toxic thiophenols is considerably important in the fields of biol. and environmental sciences. Herein, a turn-on fluorescent probe for thiophenol, named MCSH, was constructed based on a pKa shift mechanism, employing merocyanine dye as the fluorophore and 2,-4-dinitrobenzenesulfonamide (DNBS) group as the recognition unit. The imine nitrogen of MCSH has a pKa value of 4.12, which renders its non-fluorescent Schiff base form exclusively under neutral conditions. However, after reacting with thiophenols, its DNBS group was removed to afford a merocyanine dye as the final product, whose pKa value upshifts to 8.11, and was present mainly as the fluorescent protonated Schiff base form under neutral media. Such drastic change in pKa values leads to a significant fluorescence enhancement and can be utilized for the detection of thiophenols. The fluorescence intensity at 627 nm increases linearly with thiophenol concentration in the range of 0.2-3μM with a detection limit of 15 nM (S/N = 3). MCSH displays high selectivity for the detection of thiophenols over a wide range of other analytes, including aliphatic thiols. Furthermore, the preliminary applications of MCSH for monitoring thiophenols in living cells and environmental have been carried out.

Talanta published new progress about Analytical test strips. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Formula: C10H20N2O2.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Rossino, Giacomo published the artcileNew Insights into the Opening of the Occluded Ligand-Binding Pocket of Sigma1 Receptor: Binding of a Novel Bivalent RC-33 Derivative, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is human Sigma1 receptor ligand binding pocket opening RC33 derivative.

Significant progresses have been made to understand the mol. basis of the Sigma1 receptor (S1R) operating in normal and pathol. conditions. S1R is a transmembrane protein that participates in a wide variety of processes at the central nervous system; hence, its function has been associated with mental and neurol. disorders. Several ligands have been proposed to regulate the function of S1R revealing a high plasticity of the ligand-binding pocket. Previous drug-design studies have been mainly based on pharmacophore models; however, the recently revealed crystal structure of S1R provides an excellent opportunity for verifying previous predictions and for evaluating the binding of novel compounds Interestingly, the crystal structure shows that the binding pocket of S1R is highly occluded from solvent; therefore, it is not clear how ligands access this site. In the present work, we applied steered mol. dynamics (SMD) simulations to open the occluded ligand-binding pocket in the S1R crystal structure and to determine the preferred ligand pathway to enter and exit the binding site. The intracellular surface of the β-barrel ligand-binding region was found the most favorable route to accommodate ligands. This route supports the binding of RC-33 (our inhouse-developed S1R modulator) and a new bivalent derivative that constitutes the first divalent structure showed to interact with S1R. Free energy calculations of these compounds associated to S1R agree with exptl. Ki values and provide mol. insights of the binding mode of modulators that could access the S1R ligand-binding pocket through the cytoplasmic region.

Journal of Chemical Information and Modeling published new progress about Central nervous system. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem