Day: November 15, 2022

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

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

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

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

Huang, Wanrong published the artcileSubstituted 2-thioxothiazolidin-4-one derivatives showed protective effects against diabetic cataract via inhibition of aldose reductase, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is thioxo thiazolidinone derivative preparation aldose reductase inhibitor diabetic cataract; aldose reductase; cataract; docking; synthesis.

In an effort to develop a new class of potent aldose reductase inhibitors against diabetic cataracts, a series of novel 2-thioxothiazolidine-4-one derivatives was synthesized in excellent yields via a facile synthetic route. These compounds were tested against aldehyde (ALR1) and aldose reductase (ALR2) enzymes, where they showed considerable inhibitory activity. Among the tested derivatives, compound 6e showed selective and excellent inhibition of ALR2 over ALR1. The exptl. diabetes was induced by the i.p. administration of streptozotocin in male Wistar rats. Compound 6e showed pos. modulation of body weight, blood glucose, and blood insulin levels in diabetic rats. Compound 6e also showed ALR2 inhibition as evidenced by Western blot anal. in lens homogenates of Wistar rats having cataract. The docking study of 6e was also performed inside the active site of ALR2 to enumerate the key contacts for inhibitory activity.

Archiv der Pharmazie (Weinheim, Germany) published new progress about Aldose reductase inhibitors. 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

Yin, Liang published the artcileDesign and development of novel thiazole-sulfonamide derivatives as a protective agent against diabetic cataract in Wistar rats via inhibition of aldose reductase, HPLC of Formula: 73874-95-0, the main research area is benzyl piperidinyl amino thiazolyl benzenesulfonamide preparation aldose reductase inhibition.

Then development of novel thiazole-sulfonamide hybrids I [R = H, 4-Cl, 3,4-di-Cl, etc.] as a potent inhibitor of ALR2 were intended. These mols. significantly inhibited the ALR2 level in the rat lenses homogenate, where the most potent compound I [R = 4-Cl] showed activity comparable to sorbinil as standard In Wistar rats, compound I [R = 4-Cl] improved the insulin level and body weight of the exptl. animal together with a reduction in the glucose output. Compound I [R = 4-Cl] showed a significant reduction in the expression of ALR2 in rat lenses in western blot anal.

Heterocyclic Communications published new progress about Aldose reductase inhibitors. 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

Takemoto, Toshiyasu published the artcileAsymmetric synthesis of enantiomerically pure spiro [((2S)-hydroxy)indane-1,4′-piperidine], Quality Control of 137419-24-0, the main research area is spirohydroxyindanepiperidine enantioselective preparation intermediate tachykinin receptor antagonist; asym synthesis enantiomerically pure spirohydroxyindanepiperidine.

Two methods for the preparation of enantiomerically pure spirohydroxyindanepiperidine (S)-I (R = H), a key intermediate for the synthesis of a tachykinin receptor antagonist, from indenepiperidine II (R = H) are described. E.g., II (R = Me3COCO, Boc) was epoxidized with methyltrioxorhenium, the epoxide opened regioselectively to the 2-indanone derivative which was oxidized with PCC and then reduced enantioselectively in the presence of an Corey-Bakshi-Shibata oxazaborolidine catalyst to give N-Boc (S)-I (R = Boc) in 100% yield and 89% ee from the 2-indanone derivative E.g., II (R = Boc) was epoxidized enantioselectively with the (R,R)-Jacobsen epoxidation catalyst to give epoxide III in 51% yield and 91% ee; III was reduced regioselectively with ammonium formate in the presence of palladium on carbon, and the Boc derivative was then deprotected with HCl in dioxane to give the hydrochloride salt of I (R = H).

Tetrahedron: Asymmetry published new progress about Epoxidation, stereoselective. 137419-24-0 belongs to class piperidines, name is tert-Butyl spiro[indene-1,4′-piperidine]-1′-carboxylate, and the molecular formula is C18H23NO2, Quality Control of 137419-24-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Su, Wenji published the artcileTriaging of DNA-Encoded Library Selection Results by High-Throughput Resynthesis of DNA-Conjugate and Affinity Selection Mass Spectrometry, Application of tert-Butyl piperidin-4-ylcarbamate, the main research area is synthesis DNA Conjugate Mass Spectrometry.

DNA encoded library (DEL) technol. allows for rapid identification of novel small-mol. ligands and thus enables early-stage drug discovery. DEL technol. is well-established, numerous cases of discovered hit mols. have been published, and the technol. is widely employed throughout the pharmaceutical industry. Nonetheless, DEL selection results can be difficult to interpret, as library member enrichment may derive from not only desired products, but also DNA-conjugated byproducts and starting materials. Note that DELs are generally produced using split-and-pool combinatorial chem., and DNA-conjugated byproducts and starting materials cannot be removed from the library mixture Herein, we describe a method for high-throughput parallel resynthesis of DNA-conjugated mols. such that byproducts, starting materials, and desired products are produced in a single pot, using the same chem. reactions and reagents as during library production The low-complexity mixtures of DNA-conjugate are then assessed for protein binding by affinity selection mass spectrometry and the mol. weights of the binding ligands ascertained. This workflow is demonstrated to be a practical tool to triage and validate potential hits from DEL selection data.

Bioconjugate Chemistry published new progress about DNA-encoded chemical library. 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

Proto, Stefano published the artcileModel Studies on the Synthesis of Madangamine Alkaloids. Assembly of the Macrocyclic Rings, Related Products of piperidines, the main research area is diastereoselective synthesis madangamine alkaloid macrocyclic ring reductive amination lactamization; ring closing metathesis macrocyclization synthesis madangamine alkaloid ring.

Using simplified model derivatives, the assembly of the macrocyclic rings of madangamines including the 13- and 14-membered D rings of madangamines C-E, the all-cis-triunsatd. 15-membered D ring of madangamine A, and the (Z,Z)-unsaturated 11-membered E ring common to madangamines A-E, has been studied.

Organic Letters published new progress about Diastereoselective synthesis. 106118-94-9 belongs to class piperidines, name is Methyl 2-oxopiperidine-3-carboxylate, and the molecular formula is C7H11NO3, Related Products of piperidines.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Ohrui, Sayaka published the artcileDesign and synthesis of novel orexin antagonists via structural simplification of the morphinan skeleton, Product Details of C18H23NO2, the main research area is orexin ligand spiro piperidine antagonist preparation.

Herein, novel orexin antagonists with a spiro-type piperidine skeleton was designed and synthesized via removal of the unnecessary sites of orexin 1 receptor (OX1R) antagonists with a morphinan skeleton for binding to OX1R. In addition, while decahydroisoquinoline compounds with an A-ring did not show antagonistic activity for OX1R, spiro-type piperidine compounds with a dihydroindene structure showed antagonistic activities. This suggests that the lipophilic site corresponding to the A-ring of the morphinan skeleton is important for determining the antagonistic activity toward OX1R.

Heterocycles published new progress about Diastereoselective synthesis. 137419-24-0 belongs to class piperidines, name is tert-Butyl spiro[indene-1,4′-piperidine]-1′-carboxylate, and the molecular formula is C18H23NO2, Product Details of C18H23NO2.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem