Day: November 17, 2022

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

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

Liu, Ruiwu published the artcileStructure-activity relationship studies of a series of peptidomimetic ligands for α4β1 integrin on Jurkat T-leukemia cells, Application In Synthesis of 158922-07-7, the main research area is peptide solid phase synthesis SAR integrin ligand anticancer.

α4β1 Integrin is a therapeutic target for inflammation, autoimmune diseases, and lymphoid cancers. A series of peptidomimetic ligands based on the Nle-D-I motif have been synthesized and their binding affinities (IC50) to activated α4β1 integrin on Jurkat T-leukemia cells were determined using a cell adhesion assay. One of the 51 ligands, peptide I, has an IC50 = 0.6 nM, more than two fold increase of binding affinity than the initial lead compound II. Extensive SAR studies provided important information for further ligand optimization, which has served as a foundation for studies that ultimately led to identification of a potent ligand with an IC50 = 2 pM.

Biopolymers published new progress about Antitumor agents. 158922-07-7 belongs to class piperidines, name is 1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-3-carboxylic acid, and the molecular formula is C21H21NO4, Application In Synthesis of 158922-07-7.

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

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

Liu, Wen-Shan published the artcileDesign, synthesis and biological evaluation of pyridine derivatives as selective SHP2 inhibitors, SDS of cas: 73874-95-0, the main research area is tumor SHP2 inhibitor scaffold hopping ADMET mol docking binding; ADMET; Activity; Molecular docking; SHP2 inhibitor; Scaffold hopping.

SHP2 is a non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene, which affects the transduction of multiple signaling pathways, including RAS-ERK, PI3K-AKT and JAK-STAT. SHP2 also plays an important role in the programmed cell death pathway (PD-1/PD-L1). Studies have shown that SHP2 is associated with a variety of cancers, including breast, liver and gastric cancers. Therefore, the development of SHP2 inhibitors has attracted extensive attention. In this study, based on the known inhibitor 1 (SHP099), novel SHP2 inhibitors were designed by means of scaffold hopping, and 35 pyridine derivatives as SHP2 inhibitors were found. The in vitro enzyme activity assay was performed on these compounds, and multiple selective SHP2 inhibitors with activity potency similar to that of SHP099 were obtained. Among them, compound (2-(4-(aminomethyl)piperidin-1-yl)-5-(2,3-dichlorophenyl)pyridin-3-yl)methanol (11a) was the most potent and highly selective SHP2 inhibitor with an in vitro enzyme activity IC50 value of 1.36 μM. Fluorescence titration assay verified that 11a bound directly to SHP2 protein. Subsequently, cell assay of representative compounds showed that these compounds could effectively inhibit the proliferation of Ba/F3 cells. In addition, the pharmacokinetic characteristics of the designed compounds were analyzed by the in silico ADMET prediction. Mol. docking study provided more detailed information on the binding mode of compounds and SHP2 protein. In brief, this study reported for the first time that pyridine derivatives as novel SHP2 inhibitors had good inhibitory activity and selectivity, providing new clues for the development of small mol. SHP2 inhibitors.

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, SDS of cas: 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Dimitrov, Teodor published the artcileDevelopment of novel urea-based ATM kinase inhibitors with subnanomolar cellular potency and high kinome selectivity, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is urea ATM kinase inhibitor subnanomolar cellular potency kinome selectivity; ATM kinase; ATM kinase inhibitors; Cancer; DDR pathway; MD simulation; PIKK.

The ATM kinase is a key mol. regulating DNA damage response and can be targeted resulting in efficient radio- or chemosensitization. Due to the enormous size of this protein and the associated difficulties in obtaining high-quality crystal structures, we sought to develop an accurate in silico model to identify new targeting possibilities. We identified a urea group as the most beneficial chem. anchor point, which could undergo multiple interactions in the aspartate-rich hydrophobic region I of the atypical ATM kinase domain. Based on in silico data, we designed and synthesized a comprehensive set of novel urea-based inhibitors and characterized them in diverse biochem. assays. Using this strategy, we identified inhibitors with subnanomolar potency, which were further evaluated in cellular models, selectivity and early DMPK properties. Finally, the two lead compounds 34 and 39 exhibited subnanomolar cellular activity along with an excellent selectivity profile and favorable 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, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

El Abbouchi, Abdelmoula published the artcileSynthesis and biological evaluation of ethacrynic acid derivatives bearing sulfonamides as potent anti-cancer agents, Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is ethacrynic acid sulfonamide preparation anticancer human safety; Anti-cancer; Anti-proliferative; Cancer cells; Ethacrynic acid; Safety ratios; Sulfonamides.

A series of ethacrynic acid (2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetic acid) (EA, Edecrin) containing sulfonamides linked via three types of linkers namely 1,2-ethylenediamine, piperazine and 4-aminopiperidine was synthesized and subsequently evaluated in vitro against HL60 and HCT116 cancer cell lines. All the EA analogs, excluding two derivs, showed anti-proliferative activity with IC50s in the micromolar range (less than 4 uM). Three derivatives I-III were selected for their interesting dual activity on HL60 cell line in order to be further evaluated against a panel of cancer cell lines (HCT116, A549, MCF7, PC3, U87-MG and SKOV3) as well as on MRC5 as a normal cell line. These compounds displayed IC50 values in nanomolar range against A549, MCF7, PC3 and HCT116 cell lines, deducing the discovery that piperazine or 4-aminopiperidine is the linker’s best choice to develop EA analogs with highly potent anti-proliferative activities own up to 24 nM. Besides, in terms of selectivity, those linkers are more suitable offering safety ratios of up to 63.8.

Bioorganic & Medicinal Chemistry Letters 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, Name: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Brighty, Gabriel J. published the artcileUsing sulfuramidimidoyl fluorides that undergo sulfur(VI) fluoride exchange for inverse drug discovery, Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is sulfuramidimidoyl fluoride preparation inverse drug discovery cancer.

Abstract: Drug candidates that form covalent linkages with their target proteins have been underexplored compared with the conventional counterparts that modulate biol. function by reversibly binding to proteins, in part due to concerns about off-target reactivity. However, toxicity linked to off-target reactivity can be minimized by using latent electrophiles that only become activated towards covalent bond formation on binding a specific protein. Here we study sulfuramidimidoyl fluorides, a class of weak electrophiles that undergo sulfur(VI) fluoride exchange chem. We show that equilibrium binding of a sulfuramidimidoyl fluoride to a protein can allow nucleophilic attack by a specific amino acid side chain, which leads to conjugate formation. We incubated small mols., each bearing a sulfuramidimidoyl fluoride electrophile, with human cell lysate, and the protein conjugates formed were identified by affinity chromatog.-mass spectrometry. This inverse drug discovery approach identified a compound that covalently binds to and irreversibly inhibits the activity of poly(ADP-ribose) polymerase 1, an important anticancer target in living cells. [graphic not available: see fulltext]

Nature 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, Name: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

LaMarche, Matthew J. published the artcileIdentification of TNO155, an Allosteric SHP2 Inhibitor for the Treatment of Cancer, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is cancer SHP2 inhibitor drug design TNO155 clin trials.

SHP2 is a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene and is involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also plays an important role in the programed cell death pathway (PD-1/PD-L1). As an oncoprotein as well as a potential immunomodulator, controlling SHP2 activity is of high therapeutic interest. As part of our comprehensive program targeting SHP2, we identified multiple allosteric binding modes of inhibition and optimized numerous chem. scaffolds in parallel. In this drug annotation report, we detail the identification and optimization of the pyrazine class of allosteric SHP2 inhibitors. Structure and property based drug design enabled the identification of protein-ligand interactions, potent cellular inhibition, control of physicochem., pharmaceutical and selectivity properties, and potent in vivo antitumor activity. These studies culminated in the discovery of TNO155(I), (3S,4S)-8-(6-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-amine (1), a highly potent, selective, orally efficacious, and first-in-class SHP2 inhibitor currently in clin. trials for cancer.

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, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem