Category: 73874-95-0

Park, Eunsun published the artcileDiscovery and Biological Evaluation of N-Methyl-pyrrolo[2,3-b]pyridine-5-carboxamide Derivatives as JAK1-Selective Inhibitors, SDS of cas: 73874-95-0, the main research area is methyl pyrrolopyridine carboxamide preparation Janus kinase inhibitor mol docking.

Janus kinase 1 (JAK1) plays a key role in most cytokine-mediated inflammatory and autoimmune responses through JAK/STAT signaling; thus, JAK1 inhibition is a promising therapeutic strategy for several diseases. Anal. of the binding modes of current JAK inhibitors to JAK isoforms allowed the design of N-alkyl-substituted 1-H-pyrrolo[2,3-b] pyridine carboxamides I (R = H, Me, cyclopropyl, cyclopentyl) as a JAK1-selective scaffold, and the synthesis of various Me amide derivatives e.g., II, provided III as a potent JAK1-selective inhibitor. In particular, the (S,S)-enantiomer of III exhibited excellent potency for JAK1 and selectivity over JAK2, JAK3, and TYK2. On investigating the effect of III on hepatic fibrosis, it was found that it reduces the proliferation and fibrogenic gene expression of TGF-β-induced hepatic stellate cells (HSCs). Specifically, III significantly inhibited TGF-β-induced migration of HSCs at 0.25μM in wound-healing assays.

Journal of Medicinal Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 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

Onida, Killian published the artcileDirect Synthesis of Carbamoyl Fluorides by CO2 Deoxyfluorination, Category: piperidines, the main research area is carbamoyl fluoride synthesis carbon dioxide deoxyfluorination amine DAST; amines; carbamoyl fluorides; carbon dioxide; deoxyfluorination; fluorine.

Herein, a new concept for the direct synthesis of carbamoyl fluoride derivatives is disclosed. The developed method makes use of CO2 as an inexpensive and abundant C1 source; a variety of amines were successfully converted in the presence of a deoxyfluorinating reagent. The corresponding products were often obtained in excellent yields under mild reaction conditions (1 atm and room temperature). The reaction was easily scaled up, demonstrating the efficiency of the developed process.

Angewandte Chemie, International Edition published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 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

Savych, Olena published the artcileOne-Pot Parallel Synthesis of 5-(Dialkylamino)tetrazoles, Product Details of C10H20N2O2, the main research area is one pot parallel combinatorial synthesis dialkylaminotetrazole; aminotetrazole library preparation; 2,2,2-trifluoroethylthiocarbamate; REAL (readily accessible) compounds; heterocyclization; tetrazoles; thiourea.

Two protocols for the combinatorial synthesis of 5-(dialkylamino)tetrazoles were developed. The best success rate (67%) was shown by the method that used primary and secondary amines, 2,2,2-trifluoroethylthiocarbamate, and sodium azide as the starting reagents. The key steps included the formation of unsym. thiourea, subsequent alkylation with 1,3-propane sultone and cyclization with azide anion. A 559-member aminotetrazole library was synthesized by this approach; the overall readily accessible (REAL) chem. space covered by the method exceeded 7 million feasible compounds

ACS Combinatorial Science published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 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

Reddi, Rambabu N. published the artcileSite-specific labeling of endogenous proteins using CoLDR chemistry, Application of tert-Butyl piperidin-4-ylcarbamate, the main research area is site specific labeling protein CoLDR chem PROTAC fluorescence tool; Brutons tyrosine kinase active site labeling; ibrutinib evotrutinib coupling reaction amine.

Chem. modifications of native proteins can affect their stability, activity, interactions, localization, and more. However, there are few nongenetic methods for the installation of chem. modifications at a specific protein site in cells. Here we report a covalent ligand directed release (CoLDR) site-specific labeling strategy, which enables the installation of a variety of functional tags on a target protein while releasing the directing ligand. Using this approach, we were able to label various proteins such as BTK (Bruton’s tyrosine kinase), K-RasG12C, and SARS-CoV-2 PLpro with different tags. For BTK we have shown selective labeling in cells of both alkyne and fluorophores tags. Protein labeling by traditional affinity methods often inhibits protein activity since the directing ligand permanently occupies the target binding pocket. We have shown that using CoLDR chem., modification of BTK by these probes in cells preserves its activity. We demonstrated several applications for this approach including determining the half-life of BTK in its native environment with minimal perturbation, as well as quantification of BTK degradation by a noncovalent proteolysis targeting chimera (PROTAC) by in-gel fluorescence. Using an environment-sensitive “”turn-on”” fluorescent probe, we were able to monitor ligand binding to the active site of BTK. Finally, we have demonstrated efficient CoLDR-based BTK PROTACs (DC50 < 100 nM), which installed a CRBN binder onto BTK. This approach joins very few available labeling strategies that maintain the target protein activity and thus makes an important addition to the toolbox of chem. biol. Journal of the American Chemical Society published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 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

Oboh, Edmund published the artcileOptimization of the Urea Linker of Triazolopyridazine MMV665917 Results in a New Anticryptosporidial Lead with Improved Potency and Predicted hERG Safety Margin, Computed Properties of 73874-95-0, the main research area is triazolo pyridazine derivative structure linker preparation cryptosporidiosis.

Cryptosporidiosis is caused by infection of the small intestine by Cryptosporidium parasites, resulting in severe diarrhea, dehydration, malabsorption, and potentially death. The only FDA-approved therapeutic is only partially effective in young children and ineffective for immunocompromised patients. Triazolopyridazine MMV665917 is a previously reported anti-Cryptosporidium screening hit with in vivo efficacy but suffers from modest inhibition of the hERG ion channel, which could portend cardiotoxicity. Herein, we describe our initial development of structure-activity relationships of this novel lead series with a particular focus on optimization of the piperazine-urea linker. We have discovered that piperazine-acetamide is a superior linker resulting in identification of SLU-2633, which has an EC50 of 0.17μM, an improved projected margin vs. hERG, prolonged pharmacokinetic exposure in small intestine, and oral efficacy in vivo with minimal systemic exposure. SLU-2633 represents a significant advancement toward the identification of a new effective and safe treatment for cryptosporidiosis.

Journal of Medicinal Chemistry published new progress about Coccidiostats. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Computed Properties of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Temirak, Ahmed published the artcileIrreversible Antagonists for the Adenosine A2B Receptor, Related Products of piperidines, the main research area is adenosine A2B receptor antagonist sulfophenylxanthine scaffold; BRET assay; G protein activation; G protein-coupled receptor; Gα15; adenosine; covalent binding; mutagenesis; radioligand binding studies; synthesis; xanthine.

Blockade of the adenosine A2B receptor (A2BAR) represents a potential novel strategy for the immunotherapy of cancer. In the present study, we designed, synthesized, and characterized irreversible A2BAR antagonists based on an 8-p-sulfophenylxanthine scaffold. Irreversible binding was confirmed in radioligand binding and bioluminescence resonance energy transfer(BRET)-based Gα15 protein activation assays by performing ligand wash-out and kinetic experiments p-(1-Propylxanthin-8-yl)benzene sulfonyl fluoride (6a, PSB-21500) was the most potent and selective irreversible A2BAR antagonist of the present series with an apparent Ki value of 10.6 nM at the human A2BAR and >38-fold selectivity vs. the other AR subtypes. The corresponding 3-cyclopropyl-substituted xanthine derivative 6c (PSB-21502) was similarly potent, but was non-selective vs. A1- and A2AARs. Attachment of a reactive sulfonyl fluoride group to an elongated xanthine 8-substituent (12, Ki 7.37 nM) resulted in a potent, selective, reversibly binding antagonist. Based on previous docking studies, the lysine residue K2697.32 was proposed to react with the covalent antagonists. However, the mutant K269L behaved similarly to the wildtype A2BAR, indicating that 6a and related irreversible A2BAR antagonists do not interact with K2697.32. The new irreversible A2BAR antagonists will be useful tools and have the potential to be further developed as therapeutic drugs.

Molecules published new progress about Adenosine A2A receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Related Products of piperidines.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Sun, Geng published the artcileDiscovery of AdipoRon analogues as novel AMPK activators without inhibiting mitochondrial complex I, Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is AdipoRon analog preparation AMPK mitochondrial complex I diabetes; AMPK; Activator; AdipoRon; Complex I; Hypoglycemic action.

Activation of AMPK emerges as a potential therapeutic approach to metabolic diseases. AdipoRon is claimed to be an adiponectin receptor agonist that activates AMPK through adiponectin receptor 1 (AdipoR1). However, AdipoRon also exhibits moderate inhibition of mitochondrial complex I, leading to increased risk of lactic acidosis. In order to find novel AdipoRon analogs that activate AMPK without inhibition of complex I, 27 analogs of AdipoRon were designed, synthesized and biol. evaluated. As results, benzyloxy arylamide B10 was identified as a potent AMPK activator without inhibition of complex I. B10 dose-dependently improved glucose tolerance in normal mice, and significantly lowered fasting blood glucose level and ameliorated insulin resistance in db/db diabetic mice. More importantly, unlike the pan-AMPK activator MK-8722, B10 did not cause cardiac hypertrophy, probably owing to its selective activation of AMPK in the muscle tissue but not in the heart tissue. Together, B10 represents a novel class of AMPK activators with promising therapeutic potential against metabolic disease.

European Journal of Medicinal Chemistry published new progress about AMP-activated protein kinase activators. 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

Ishida, Akiharu published the artcileDesign, synthesis, and biological evaluation of novel somatostatin receptor subtype-2 agonists: Optimization for potency and risk mitigation of hERG and phospholipidosis, Safety of tert-Butyl piperidin-4-ylcarbamate, the main research area is ERG phospholipidosis somatostatin receptor subtype 2 agonist; Agonist; G-protein coupled receptor (GPCR); PKa; Phospholipidosis; SSTR2; Somatostatin; cLogP; hERG.

Somatostatin receptors are members of G-protein coupled receptor superfamily. Receptors can be classified into five subtypes, SSTR1 to 5. The highly potent and orally active SSTR2 agonist 7, which had been identified by our group, was found out to have toxicol. liabilities such as hERG inhibition and phospholipidosis (PLD). We investigated the relationship between in silico physicochem. properties and hERG and PLD, and explored well-balanced agonists to identify amide 19 and benzimidazole 30. As a result of this exploration, we found out that the value of (cLogP) [2] + (pKa) [2] needs to be less than 110 to mitigate the liabilities.

Bioorganic & Medicinal Chemistry published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (ERG). 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

Chen, Ying-Chu published the artcileC-N Coupling of DNA-Conjugated (Hetero)aryl Bromides and Chlorides for DNA-Encoded Chemical Library Synthesis, Computed Properties of 73874-95-0, the main research area is DNA encoded heteroaryl amide library synthesis.

DNA-encoded chem. library (DECL) screens are a rapid and economical tool to identify chem. starting points for drug discovery. As a robust transformation for drug discovery, palladium-catalyzed C-N coupling is a valuable synthetic method for the construction of DECL chem. matter; however, currently disclosed methods have only been demonstrated on DNA-attached (hetero)aromatic iodide and bromide electrophiles. We developed conditions utilizing an N-heterocyclic carbene-palladium catalyst that extends this reaction to the coupling of DNA-conjugated (hetero)aromatic chlorides with (hetero)aromatic and select aliphatic amine nucleophiles. In addition, we evaluated steric and electronic effects within this catalyst series, carried out a large substrate scope study on two representative (hetero)aryl bromides, and applied this newly developed method within the construction of a 63 million-membered DECL.

Bioconjugate Chemistry published new progress about Anilines Role: CMB (Combinatorial Study), RCT (Reactant), RACT (Reactant or Reagent). 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Computed Properties of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Canale, Vittorio published the artcileSustainable Synthesis of a Potent and Selective 5-HT7 Receptor Antagonist Using a Mechanochemical Approach, Quality Control of 73874-95-0, the main research area is benzenesulfonamide PZ1361 synthesis antidepressant serotonin 5HT7 receptor.

A mechanochem. procedure was developed to obtain PZ-1361, a potent and selective 5-HT7 receptor antagonist, with antidepressant properties in rodents. The elaborated protocol offered several advantages over classical batch synthesis, including improvement of the overall yield (from 34% to 64%), reduction of reaction time (from 60 to 5.5 h), limitation of the use of toxic solvents, and the formation of byproducts. This approach represents a rare example of the synthesis of biol. active compounds exclusively performed using mechanochem. reactions.

Journal of Organic Chemistry published new progress about 5-HT7 receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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