Tag: M.W=200-250

Sun, Ning published the artcileDevelopment of a Brigatinib degrader (SIAIS117) as a potential treatment for ALK positive cancer resistance, Application of tert-Butyl piperidin-4-ylcarbamate, the main research area is brigatinib PROTAC preparation ALK pos cancer resistance; ALCL; ALK; Brigatinib; Degrader; NSCLC; PROTAC; Resistance; VHL.

EML4-ALK and NPM-ALK fusion proteins possess constitutively activated ALK (anaplastic lymphoma kinase) activity, which in turn leads to the development of non-small cell lung cancer and anaplastic large-cell lymphomas (ALCLs). FDA-approved ALK inhibitor drugs cause significant cancer regression. However, drug resistance eventually occurs and it becomes a big obstacle in clinic. Novel proteolysis targeting chimera (PROTAC) technol. platform provides a potential therapeutic strategy for drug resistance. Herein, we designed and synthesized a series of ALK PROTACs based on Brigatinib and VHL-1 conjunction, and screened SIAIS117 as the best degrader which not only blocked the growth of SR and H2228 cancer cell lines, but also degraded ALK protein. In addition, SIAIS117 also showed much better growth inhibition effect than Brigatinib on 293T cell line that exogenously expressed G1202R-resistant ALK proteins. Furthermore, it also degraded G1202R mutant ALK protein in vitro. At last, it has the potentially anti-proliferation ability of small cell lung cancer. Thus, we have successfully generated the degrader SIAIS117 that can potentially overcome resistance in cancer targeted therapy.

European Journal of Medicinal Chemistry published new progress about Antitumor agent resistance. 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

Cagli, Eda published the artcileAn experimental and computational approach to pH-dependent self-aggregation of poly(2-isopropyl-2-oxazoline), Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is polyisopropyl oxazoline pH self assembly water interaction DFT.

Besides temperature, self-aggregation of poly(2-isopropyl-2-oxazoline) (PIPOX) can also be triggered via pH in aqueous solution (25°, pH > 5). Lowest energy structures and interaction energies of PIPOX with H3O+, OH-, and H2O were calculated by DFT methods showed that, in addition to their ability to protonate PIPOX, H3O+ ions had strong interaction with both H2O and PIPOX in acidic conditions. H3O+ ions acted as compatibilizer between PIPOX and H2O and increased the solubility of PIPOX. OH- ions have stronger interaction with H2O compared to PIPOX resulting in desorption of H2O mols. from PIPOX phase and decreased solubility, leading to enhanced hydrophobic interactions among Me2CH groups of PIPOX and formation of aggregates at high pH. Results concerning the effect of end-groups on aggregate size were in good agreement with statistical mechanics calculations Also, the effect of polymer concentration on the aggregate size was examined © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018.

Journal of Polymer Science, Part B: Polymer Physics published new progress about Density functional theory. 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

Rabal, Obdulia published the artcileDesign and Synthesis of Novel Epigenetic Inhibitors Targeting Histone Deacetylases, DNA Methyltransferase 1, and Lysine Methyltransferase G9a with In Vivo Efficacy in Multiple Myeloma, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is histone deacetylases DNA methyltransferase G9a inhibitors multiple myeloma antitumor.

Concomitant inhibition of key epigenetic pathways involved in silencing tumor suppressor genes has been recognized as a promising strategy for cancer therapy. Herein, we report a first-in-class series of quinoline-based analogs that simultaneously inhibit histone deacetylases (from a low nanomolar range) and DNA methyltransferase-1 (from a mid-nanomolar range, IC50 < 200 nM). Addnl., lysine methyltransferase G9a inhibitory activity is achieved (from a low nanomolar range) by introduction of a key lysine mimic group at the 7-position of the quinoline ring. The corresponding epigenetic functional cellular responses are observed: histone-3 acetylation, DNA hypomethylation, and decreased histone-3 methylation at lysine-9. These chem. probes, multi-target epigenetic inhibitors, were validated against the multiple myeloma cell line MM1.S, demonstrating promising in vitro activity of 12a (CM-444) with GI50 of 32 nM, an adequate therapeutic window (>1 log unit), and a suitable pharmacokinetic profile. In vivo, 12a achieved significant antitumor efficacy in a xenograft mouse model of human multiple myeloma.

Journal of Medicinal Chemistry published new progress about Acetylation (histone H3). 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

Liu, Xuwen published the artcileSynthesis and structure-activity relationships of thieno[2,3-d]pyrimidines as atypical protein kinase C inhibitors to control retinal vascular permeability and cytokine-induced edema, COA of Formula: C10H20N2O2, the main research area is structure preparation thieno pyrimidine derivative aPKC retinal vascular permeability; Blinding eye diseases; Homology model; SAR; Thieno[2,3-d]pyrimidine inhibitors; Tumor necrosis factor-α (TNFα); Vascular endothelial growth factor (VEGF); Vascular permeability; atypical protein kinase C (aPKC).

Studies demonstrate that small mol. targeting of atypical protein kinase C (aPKC) may provide an effective means to control vascular permeability, prevent edema, and reduce inflammation providing novel and important alternatives to anti-VEGF therapies for certain blinding eye diseases. Based on a literature tricyclic thieno[2,3-d]pyrimidine lead (1), an ATP-competitive inhibitor of the aPKC iota (ι) and aPKC zeta (ζ) isoforms, we have synthesized a small series of compounds in 1-2 steps from a readily available chloro intermediate. A single pyridine congener was also made using 2D NMR to assign regiochem. Within the parent pyrimidine series, a range of potencies was observed against aPKCζ whereas the pyridine congener was inactive. Selected compounds were also tested for their effect toward VEGF-induced permeability in BREC cells. The most potent of these (7l) was further assayed against the aPKCι isoform and showed a favorable selectivity profile against a panel of 31 kinases, including kinases from the AGC superfamily, with a focus on PKC isoforms and kinases previously shown to affect permeability. Further testing of 7l in a luciferase assay in HEK293 cells showed an ability to prevent TNF-α induced NFκB activation while not having any effect on cell survival. Intravitreal administration of 7l to the eye yielded a complete reduction in permeability in a test to determine whether the compound could block VEGF- and TNFα-induced permeability across the retinal vasculature in a rat model. The compound in mice displayed good microsomal stability and in plasma moderate exposure (AUC and Cmax), low clearance, a long half-life and high oral bioavailability. With IV dosing, higher levels were observed in the brain and eye relative to plasma, with highest levels in the eye by either IV or PO dosing. With a slow oral absorption profile, 7l accumulates in the eye to maintain a high concentration after dosing with higher levels than in plasma. Compound 7l may represent a class of aPKC inhibitors for further investigation.

Bioorganic & Medicinal Chemistry published new progress about Anti-inflammatory 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

Du, Qianming published the artcileDiscovery of phosphonamidate IDO1 inhibitors for the treatment of non-small cell lung cancer, SDS of cas: 73874-95-0, the main research area is phosphonamidate IDO1 inhibitor preparation antitumor human lung non small; Epacadostat; IDO1 inhibitors; IDO2; Phosphonamidate ester; TDO.

Targeting indoleamine 2,3-dioxygenase 1 (IDO1) has been identified as an attractive approach for the development of cancer immunotherapy. In this study, a series of phosphonamidate ester containing compounds were designed, synthesized and evaluated for their inhibitory activities against IDO1. Among them, compounds 16, 17, and 26 with good IDO1 inhibitory (HeLa IDO1 IC50 = 10-21 nM, hIDO1 IC50 = 78-121 nM) activities were selected for further investigation and showed good physicochem. properties. Furthermore, based on comparable PK profile and excellent IDO2/TDO inhibitory potency, representative compound 16 was selected for further bio-evaluation and characterized with good efficacy in suppressing lung metastasis (77% inhibition rate) of Lewis cells in vivo. Thus, compound 16 could be a potential and efficacious agent for further evaluation.

European Journal of Medicinal Chemistry published new progress about Antitumor agents (cervix, lung). 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

Ren, Chaowei published the artcileStructure-based discovery of SIAIS001 as an oral bioavailability ALK degrader constructed from Alectinib, Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is anaplastic lymphoma kinase alectinib preparation anticancer oral bioavailability; Alectinib; Anaplastic large-cell lymphomas; Anaplastic lymphoma kinase; CRBN; Oral bioavailability; Proteolysis targeting chimeras.

Fusion proteins of the anaplastic lymphoma kinase (ALK) are promising therapeutic targets for cancer and other human diseases, especially for non-small cell lung cancer (NSCLC) and anaplastic large-cell lymphomas (ALCLs). Herein a structure-based design, synthesis, and evaluation of ALK PROTACs (proteolysis-targeting chimeras) based on Alectinib, as the warhead were described. CRBN ligands as the E3 ligase moiety were screened first, used to obtain a series of potent ALK degraders based on different CRBN ligands, and exemplified by SIAIS091 and SIAIS001 with lenalidomide/thalidomide-based linkers. Both of them induced effective ALK degradation at low nanomolar concentrations in cells, and showed much better growth inhibition effects than Alectinib. SIAIS091 or SIAIS001 also promoted cell cycle arrest in G1/S phase. Finally, SIAIS001 exhibited good oral bioavailability in Pharmacokinetics study.

European Journal of Medicinal Chemistry published new progress about Anaplastic large-cell lymphoma. 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

Bongard, Jens published the artcileChemical Validation of DegS As a Target for the Development of Antibiotics with a Novel Mode of Action, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is DegS drug target antibiotic preparation; antibiotics; drug discovery; small molecules; synergism; synthesis.

Despite the availability of hundreds of antibiotic drugs, infectious diseases continue to remain one of the most notorious health issues. In addition, the disparity between the spread of multidrug-resistant pathogens and the development of novel classes of antibiotics exemplify an important unmet medical need that can only be addressed by identifying novel targets. Herein we demonstrate, by the development of the first in vivo active DegS inhibitors based on a pyrazolo[1,5-a]-1,3,5-triazine scaffold, that the serine protease DegS and the cell envelope stress-response pathway σE represent a target for generating antibiotics with a novel mode of action. Moreover, DegS inhibition is synergistic with well-established membrane-perturbing antibiotics, thereby opening promising avenues for rational antibiotic drug design.

ChemMedChem published new progress about Antibacterial agent resistance. 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

Wang, Ying published the artcileThe Use of Potassium/Sodium Nitrite as a Nitrosating Agent in the Electrooxidative N-Nitrosation of Secondary Amines, Application In Synthesis of 73874-95-0, the main research area is nitroso compound preparation; secondary amine potassium nitrite electrooxidative nitrosation.

The electrochem. N-nitrosation of secondary amines, e.g., 1-phenylpiperazine using widely available sodium/potassium nitrite as a nitrosating agent has been described. This approach not only eliminates the need for using a combination of sodium/potassium and a strong acid but also has good functional group tolerance. The reaction is compatible with the late-stage modification of pharmaceutical compounds, e.g., I and could be conducted in gram scale with a high reaction efficiency. Preliminary mechanistic studies indicate that the N-nitrosation occurs via the anodic oxidation of KNO2 into an NO2 radical which is then transformed into an NO+ cation.

European Journal of Organic Chemistry published new progress about Nitrosation (electrooxidative). 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

Amato, George published the artcileFunctionalized 6-(Piperidin-1-yl)-8,9-Diphenyl Purines as Peripherally Restricted Inverse Agonists of the CB1 Receptor, HPLC of Formula: 73874-95-0, the main research area is piperidinyl diphenyl purine preparation CB1 receptor alc liver steatosis.

Peripherally restricted CB1 receptor antagonists may be useful in treating metabolic syndrome, diabetes, liver diseases, and gastrointestinal disorders. Clin. development of the centrally acting CB1 inverse agonist otenabant (1) was halted due to its potential of producing adverse effects. SAR studies of 1 are reported herein with the objective of producing peripherally restricted analogs. Crystal structures of hCB1 and docking studies with 1 indicate that the piperidine group could be functionalized at the 4-position to access a binding pocket that can accommodate both polar and nonpolar groups. The piperidine is studied as a linker, functionalized with alkyl, heteroalkyl, aryl, and heteroaryl groups using a urea connector. Orally bioavailable and peripherally selective compounds have been produced that are potent inverse agonists of hCB1 with exceptional selectivity for hCB1 over hCB2. Compound 38 blocked alc.-induced liver steatosis in mice and has good ADME properties for further development.

Journal of Medicinal Chemistry published new progress about Alcoholic fatty liver disease. 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

Kalinin, Stanislav published the artcileHighly hydrophilic 1,3-oxazol-5-yl benzenesulfonamide inhibitors of carbonic anhydrase II for reduction of glaucoma-related intraocular pressure, Formula: C10H20N2O2, the main research area is glaucoma intraocular pressure CA inhibitors hydrophilicity non corneal absorption; Carbonic anhydrase inhibitors; Glaucoma; Hydrophilicity; Intraocular delivery; Intraocular pressure; Non-corneal absorption.

Four inhibitors of human carbonic anhydrase II (hCA II) were designed based on the previously reported subnanomolar 1,3-oxazole-based sulfonamide inhibitors of the enzyme to incorporate primary and secondary amine functionality in the carboxamide side chain. The new hydrophilic compounds were found to inhibit the target isoform in sub-nanomolar to low nanomolar range with a good degree of selectivity to several other hCA isoforms. The hydrophilic character of these compounds is advantageous for intraocular residence time but not for corneal permeability which generally requires that a drug be sufficiently lipophilic. Two of the four compounds investigated, however, were found to exert comparable efficacy as 1% eye drops in PBS to that of the clin. used 2% dorzolamide (Trusopt) eye drops. This indicated that the absorption of the compounds may occur via alternative route across conjunctiva and sclera.

Bioorganic & Medicinal Chemistry published new progress about Carbonic anhydrase inhibitors. 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