Tag: M.W=200-250

Yang, Tao published the artcileDiscovery of Potent and Orally Effective Dual Janus Kinase 2/FLT3 Inhibitors for the Treatment of Acute Myelogenous Leukemia and Myeloproliferative Neoplasms, HPLC of Formula: 73874-95-0, the main research area is pyrazolyl pyrimidine arylamino preparation kinase inhibitor myelogenous leukemia.

Herein, the design, synthesis, and structure-activity relationships of a series of unique 4-(1H-pyrazol-4-yl)-pyrimidin-2-amine derivatives that selectively inhibit Janus kinase 2 (JAK2) and FLT3 kinases is described. These screening cascades revealed that I was a preferred compound with IC50 values of 0.7 and 4 nM for JAK2 and FLT3, resp. Moreover, I was a potent JAK2 inhibitor with 37-fold and 56-fold selectivity over JAK1 and JAK3, resp., and possessed an excellent selectivity profile over the other 100 representative kinases. In a series of cytokine-stimulated cell-based assays, I exhibited a higher JAK2 selectivity over other JAK isoforms. The oral administration of 60 mg/kg of I could significantly inhibit tumor growth, with a tumor growth inhibition rate of 93 and 85% in MV4-11 and SET-2 xenograft models, resp. Addnl., I showed an excellent bioavailability (F = 58%), a suitable half-life time (T1/2 = 4.1 h), a satisfactory metabolic stability, and a weak CYP3A4 inhibitory activity, suggesting that I might be a potential drug candidate for JAK2-driven myeloproliferative neoplasms and FLT3-internal tandem duplication-driven acute myelogenous leukemia.

Journal of Medicinal Chemistry published new progress about Antitumor 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

Tikhomirov, Alexander S. published the artcileAmides of pyrrole- and thiophene-fused anthraquinone derivatives: a role of the heterocyclic core in antitumor properties, Category: piperidines, the main research area is naphthoindole carboxamide preparation human SAR antitumor mol docking; anthrathiophene carboxamide preparation human SAR antitumor mol docking; Anthraquinone; Antitumor activity; Apoptosis; DNA binding; Indole; Multidrug resistance; Reactive oxygen species; Structure-activity relationship; Thiophene; Topoisomerase 1.

A new series of naphtho[2,3-f]indole-3-carboxamides I [R1 = Me; R2 = (3S)-3-aminopyrrolidin-1-yl, ((3S)-pyrrolidin-3-yl)amino, 4-amino-1-piperidyl, etc.; X = NH, NMe, NBn, etc.;] and anthra[2,3-b]thiophene-3-carboxamides I [R1 = H, X = S] was synthesized via coupling the resp. acids with cyclic diamines and dissected the role of the heterocyclic core in antitumor properties. New compounds demonstrated a submicromolar antiproliferative potency close to doxorubicin (Dox) against five tumor cell lines of various tissue origin. In contrast to Dox, the new compounds were similarly cytotoxic for HCT116 colon carcinoma cells (wild type p53) and their isogenic p53 knockout counterparts. Compound I [R1 = Me; R2 = (3S)-3-aminopyrrolidin-1-yl; X = NH] formed more affine complexes with DNA duplex than furan and thiophene analogs, a property that could be translated into a stronger inhibition of topoisomerase 1 mediated DNA unwinding. At tolerable doses the water soluble derivative I [R1 = Me; R2 = (3S)-3-aminopyrrolidin-1-yl; X = NH] significantly inhibited tumor growth (up to 79%) and increased the lifespan (153%) of mice bearing P388 lymphoma transplants.

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

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Qin, Qiaohua published the artcileDiscovery of 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4: Biological evaluation and docking studies, Product Details of C10H20N2O2, the main research area is diaminopyrimidine synthesis anticancer structure activity PAK4 cancer; PAK4; anticancer; docking study; inhibitors.

In this study, novel 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4 (PAK4) were discovered and evaluated for their biol. activity against PAK4. Among the derivatives studied, promising compounds A2, B6, and B8 displayed the highest inhibitory activities against PAK4 (IC50 = 18.4, 5.9, and 20.4 nM, resp.). From the cellular assay, compound B6 exhibited the highest potency with an IC50 value of 2.533μM against A549 cells. Some compounds were selected for computational ADME (absorption, distribution, metabolism, and elimination) properties and mol. docking studies against PAK4. The detailed structure-activity relationship based on the biochem. activities and mol. docking studies were explored. According to the docking studies, compound B6 had the lowest docking score (docking energy: -7.593 kcal/mol). The mol. docking simulation indicated the binding mode between compound B6 and PAK4. All these results suggest compound B6 as a useful candidate for the development of a PAK4 inhibitor.

Archiv der Pharmazie (Weinheim, Germany) published new progress about Antitumor 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

Plewe, Michael B. published the artcileDiscovery of Adamantane Carboxamides as Ebola Virus Cell Entry and Glycoprotein Inhibitors, Application of tert-Butyl piperidin-4-ylcarbamate, the main research area is ebola virus glycoprotein cell entry adamantane carboxamide SAR.

We identified and explored the structure-activity-relationship (SAR) of an adamantane carboxamide chem. series of Ebola virus (EBOV) inhibitors. Selected analogs exhibited half-maximal inhibitory concentrations (EC50 values) of ~10-15 nM in vesicular stomatitis virus (VSV) pseudotyped EBOV (pEBOV) infectivity assays, low hundred nanomolar EC50 activity against wild type EBOV, aqueous solubility >20 mg/mL, and attractive metabolic stability in human and nonhuman liver microsomes. X-ray cocrystallog. characterizations of a lead compound with the EBOV glycoprotein (GP) established the EBOV GP as a target for direct compound inhibitory activity and further provided relevant structural models that may assist in identifying optimized therapeutic candidates.

ACS Medicinal Chemistry Letters published new progress about Antiviral agents. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Application of tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Lei, Ning published the artcileElectrochemical Iodoamination of Indoles Using Unactivated Amines, Formula: C10H20N2O2, the main research area is green electrochem iodoamination indole unactivated amine amino acid benzotriazole.

An environmentally friendly electrochem. approach for iodoamination of various indole derivatives with a series of unactivated amines, amino acid derivatives, and benzotriazoles (more than 80 examples) has been developed. This strategy was further applied in late-stage functionalization of natural products and pharmaceuticals and gram-scale synthesis and radiosynthesis of 131I-labeled compounds Fundamental insights into the mechanism of the reaction based on control experiments, d. functional theory calculation, and cyclic voltammetry are provided.

Organic Letters published new progress about Amination (iodo). 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

Zhao, Min published the artcileSynthesis and evaluation of new compounds bearing 3-(4-aminopiperidin-1-yl)methyl magnolol scaffold as anticancer agents for the treatment of non-small cell lung cancer via targeting autophagy, COA of Formula: C10H20N2O2, the main research area is magnolol aminopiperidinylmethyl preparation anticancer non small cell lung cancer; Autophagy; Magnolia officinalis; Magonolol; Non-small cell lung cancer.

Magnolol and honokiol are the two major active ingredients with similar structure and anticancer activity from traditional Chinese medicine Magnolia officinalis, and honokiol is now in a phase I clin. trial (CTR20170822) for advanced non-small cell lung cancer (NSCLC). In search of potent lead compounds with better activity, our previous study has demonstrated that magnolol derivative 3-(4-aminopiperidin-1-yl)methyl magnolol has better activity than honokiol. Here, based on the core of 3-(4-aminopiperidin-1-yl)methyl magnolol, we synthesized fifty-one magnolol derivatives Among them, compound I exhibited the most potent antiproliferative activities on H460, HCC827, H1975 cell lines with the IC50 values of 0.63-0.93μM, which were approx. 10- and 100-fold more potent than those of C2 and magnolol, resp. Besides, oral administration of I and C2 on an H460 xenograft model also demonstrated that I has better activity than C2. Mechanism study revealed that I induced G0/G1 phase cell cycle arrest, apoptosis and autophagy in cancer cells. Moreover, blocking autophagy by the autophagic inhibitor enhanced the anticancer activity of I in vitro and in vivo, suggesting autophagy played a cytoprotective role on I-induced cancer cell death. Taken together, our study implied that compound I combined with autophagic inhibitor could be another choice for NSCLC treatment in further investigation.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 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

Liu, Yang published the artcileExtensive investigation of benzylic N-containing substituents on the pyrrolopyrimidine skeleton as Akt inhibitors with potent anticancer activity, Application In Synthesis of 73874-95-0, the main research area is anticancer Akt docking mantle cell lymphoma cytotoxicities antiproliferative; Akt; Anticancer; Docking; Mantle cell lymphoma; Pyrrolopyrimidines.

Continuous optimization of benzylic substituents on 1-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl)-2-phenylethan-1-one structure as Akt inhibitors was described in this paper. Particularly, compounds 8 and 14g exhibited high enzymic potency against all Akt isoforms and antiproliferative effects in mantle cell lymphoma cell lines, as well as favorable cytotoxicities in patient primary cancer cells. Low micromolar doses of both 8 and 14g dose-dependently induced cell apoptosis and G2/M cell cycle arrest, also suppressed the phosphorylation level of Akt downstream targets GSK3β and S6.

Bioorganic Chemistry published new progress about Antitumor agents. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Application In Synthesis of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Pan, Chenghao published the artcileDesign, synthesis and biological evaluation of quinazoline derivatives as potent and selective FGFR4 inhibitors, SDS of cas: 73874-95-0, the main research area is hepatocellular carcinoma FGFR4 inhibitor quinazoline derivative anticancer; FGFR4 inhibitors; Hepatocellular carcinoma (HCC); Solvent region modification.

Aberrant activation of the fibroblast growth factor 19-fibroblast growth factor receptor 4 (FGF19-FGFR4) signaling pathway has been proved to promote hepatocellular carcinoma (HCC) proliferation. It is assumed that the first FGFR4 inhibitor BLU9931 did not enter clin. studies, presumably due to its rapid metabolism in liver microsomes. Here, we report the development of series of quinazoline derivatives based on FGFR4 inhibitor BLU9931 through structural modification of its solvent region pocket to minimize its potential metabolic liability. Among them, compound 35a exhibited comparable or superior kinase inhibitory activity (IC50 = 8.5 nM) and selectivity in cells. More importantly, compound 35a improved liver microsomes stability compared to BLU9931. Cellular mechanistic studies demonstrated that 35a induced apoptosis via the FGFR4 signaling pathway blockage. In addition, the computational simulation revealed the possible binding mode to FGFR4 protein, which provides a plausible explanation of high potent and metabolic stability.

European Journal of Medicinal Chemistry published new progress about Antitumor 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

Yu, Jiang published the artcileStructure-based design, synthesis, and evaluation of inhibitors with high selectivity for PARP-1 over PARP-2, Quality Control of 73874-95-0, the main research area is azepino indolone design synthesis mol docking anticancer PARP selectivity; Cancer; PARP-1 inhibitor; Rucaparib analogues; Selectivity; Structure based design.

The poly (ADP-ribose) polymerase (PARP) inhibitors play a crucial role in cancer therapy. However, most approved PARP inhibitors have lower selectivity to PARP-1 than to PARP-2, so they will inevitably have side effects. Based on the different catalytic domains of PARP-1 and PARP-2, we developed a strategy to design and synthesize highly selective PARP-1 inhibitors. A few selected compounds (labeled Y17, Y29, Y31 and Y49) showed excellent PARP-1 inhibition, and their IC50 values were 0.61, 0.66, 0.41 and 0.96 nM, resp. Then, Y49 (PARP-1 IC50 = 0.96 nM, PARP-2 IC50 = 61.90 nM, selectivity PARP-2/PARP-1 = 64.5) was proved to be the most selective inhibitor of PARP-1. Compounds Y29 and Y49 showed stronger inhibitory effect on proliferation in BRCA1 mutant MX-1 cells than in other cancer cells. In the MDA-MB-436 xenotransplantation model, Y49 was well tolerated and showed remarkable single dose activity. The design strategy proposed in this paper is of far-reaching significance for the further construction of the next generation of selective PARP-1 inhibitors.

European Journal of Medicinal Chemistry published new progress about Antitumor 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

Zhou, Zhe published the artcileTargeted degradation of CD147 proteins in melanoma, Safety of tert-Butyl piperidin-4-ylcarbamate, the main research area is CD147 PROTAC pseudolaric acid B derivative; CD147; Degradation; Melanoma; PROTAC; Pseudolaric Acid B.

CD147 is a transmembrane glycoprotein and a member of Ig superfamily, is strongly expressed in melanoma cells. CD147 has a pivotal role in tumor development. Therefore, it is a potential drug target for melanoma. In this article, we report the discovery of the first CD147 protein proteolysis targeting chimeras (PROTACs) derived from the natural product pseudolaric acid B (PAB). The representative compound 6a (I) effectively induced degradation of CD147 and inhibited melanoma cells in vitro and in vivo. 6A could be used as the novel type of anticancer agent or as a part of the mol. biol. research toolkit used in the gain-of-function study of the dynamic roles of CD147 in cancer networks.

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

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem