Month: November 2022

Gastaldi, Simone published the artcileChemical Modulation of the 1-(Piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Scaffold as a Novel NLRP3 Inhibitor, Safety of tert-Butyl piperidin-4-ylcarbamate, the main research area is piperidinyl dihydro benzoimidazoleone scaffold chem modulation; ATP hydrolysis; MD simulations; NLRP3 inhibitors; interleukin-1β; pyroptosis.

In the search for new chem. scaffolds able to afford NLRP3 inflammasome inhibitors, we used a pharmacophore-hybridization strategy by combining the structure of the acrylic acid derivative INF39 with the 1-(piperidin-4-yl)1,3-dihydro-2H-benzo[d]imidazole-2-one substructure present in HS203873, a recently identified NLRP3 binder. A series of differently modulated benzo[d]imidazole-2-one derivatives were designed and synthesized. The obtained compounds were screened in vitro to test their ability to inhibit NLRP3-dependent pyroptosis and IL-1β release in PMA-differentiated THP-1 cells stimulated with LPS/ATP. The selected compounds were evaluated for their ability to reduce the ATPase activity of human recombinant NLRP3 using a newly developed assay. From this screening, compounds 9, 13 and 18, able to concentration-dependently inhibit IL-1β release in LPS/ATP-stimulated human macrophages, emerged as the most promising NLRP3 inhibitors of the series. Computational simulations were applied for building the first complete model of the NLRP3 inactive state and for identifying possible binding sites available to the tested compounds The analyses led us to suggest a mechanism of protein-ligand binding that might explain the activity of the compounds

Molecules published new progress about Cryopyrin 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, Safety of tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Zheng, Xiaoli published the artcileCondensation of 2-((Alkylthio)(aryl)methylene)malononitrile with 1,2-Aminothiol as a Novel Bioorthogonal Reaction for Site-Specific Protein Modification and Peptide Cyclization, HPLC of Formula: 73874-95-0, the main research area is sequence alkylthio aryl methylene malononitrile aminothiol bioorthogonal reaction; bioorthogonal reaction protein modification peptide cyclization.

Site-specific modification of peptides and proteins has wide applications in probing and perturbing biol. systems. Herein we report that 1,2-aminothiol can react rapidly, specifically and efficiently with 2-((alkylthio)(aryl)methylene)malononitrile (TAMM) under biocompatible conditions. This reaction undergoes a unique mechanism involving thiol-vinyl sulfide exchange, cyclization, and elimination of dicyanomethanide to form 2-aryl-4,5-dihydrothiazole (ADT) as a stable product. An 1,2-aminothiol functionality can be introduced into a peptide or a protein as an N-terminal cysteine or an unnatural amino acid. The bioorthogonality of this reaction was demonstrated by site-specific labeling of not only synthetic peptides and a purified recombinant protein but also proteins on mammalian cells and phages. Unlike other reagents in bioorthogonal reactions, the chem. and phys. properties of TAMM can be easily tuned. TAMM can also be applied to generate phage-based ADT-cyclic peptide libraries without reducing phage infectivity. Using this approach, we identified ADT-cyclic peptides with high affinity to different protein targets, providing valuable tools for biol. studies and potential therapeutics. Furthermore, the mild reaction conditions of TAMM condensation warrant its use with other bioorthogonal reactions to simultaneously achieve multiple site-specific modifications.

Journal of the American Chemical Society published new progress about Bcl-2 proteins 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, HPLC of Formula: 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Song, Aimin published the artcileA Novel and Rapid Encoding Method Based on Mass Spectrometry for “”One-Bead-One-Compound”” Small Molecule Combinatorial Libraries, SDS of cas: 158922-07-7, the main research area is combinatorial library decoding technique mass spectrometry; solid phase synthesis decoding combinatorial library mass spectroscopy; coding block synthesis deconvolution combinatorial library solid phase; single bead decoding combinatorial library.

A method for the preparation and encoding of readily deconvoluted combinatorial libraries is discussed. Beads are prepared with topol. segregated regions – an inner region to which is bound coding tags and an outer segment to which the library compound is bound. Coding blocks are attached to the inner resin by a cleavable methionine-containing linker; the coding blocks are chosen to have similar reactivities to the building blocks incorporated in the synthesis of the combinatorial library. Synthesis of the library leads to the functionalization of the library-containing portion of the resin bead and the coding portion of the resin bead. Cleavage of the linkers for the coding blocks from the resin bead by Edman degradation with cyanogen bromide yields lactones whose mass is determined by FT-MALDI mass spectroscopy. Anal. of the lactones isolated from a given bead yields the mass of each of the fragments present; by careful choice of coding blocks and reactants, the identities of the building blocks incorporated into a library bead and of the library member attached to that bead can be readily derived from the fragment masses. A combinatorial library is prepared and tested for the binding of library members to streptavidin; seventeen of the compounds are found to bind strongly to streptavidin by a colorometric assay and identified unambiguously by the library encoding method described here.

Journal of the American Chemical Society published new progress about Amines Role: CMB (Combinatorial Study), RCT (Reactant), RACT (Reactant or Reagent). 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, SDS of cas: 158922-07-7.

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

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

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

Deng, Hongfeng published the artcilePotent Cannabinergic Indole Analogues as Radioiodinatable Brain Imaging Agents for the CB1 Cannabinoid Receptor, Application In Synthesis of 27483-92-7, the main research area is indole iodobenzoyl piperidinylmethyl radioiodinated preparation CB1 cannabinoid receptor agonist; iodine labeled indole brain imaging agent.

A series of novel aminoalkylindoles was synthesized in an effort to develop compounds that are potent agonists at the CB1 cannabinoid receptor and that are also easily labeled with radioisotopes of iodine for biochem. and imaging studies. 2-Iodophenyl-[1-(1-methylpiperidin-2-ylmethyl)-1H-indol-3-yl]methanone I (AM2233) had a very high affinity for the rat CB1 receptor, with most of the affinity residing with the (R)-enantiomer. Radioiodinated racemic I and its enantiomers were prepared by radioiododestannylation of the tributyltin analogs in high yields, radiochem. purities, and specific radioactivities. In a mouse hippocampal membrane preparation with [131I](R)-I as radioligand, racemic I exhibited a Ki value of 0.2 nM compared with 1.6 nM for WIN55212-2. In autoradiog. experiments with mouse brain sections, the distribution of radioiodinated I was consistent with that of brain CB1 receptors. Again, very little specific binding was seen with the (S)-enantiomer [131I](S)-I and none occurred with the (R)-enantiomer [131I](R)-I in sections from CB1 receptor knockout mice. Radioiodinated I thus appears to be a suitable radioligand for studies of CB1 cannabinoid receptors.

Journal of Medicinal Chemistry published new progress about Labeled chemical compounds Role: DGN (Diagnostic Use), PAC (Pharmacological Activity), SPN (Synthetic Preparation), BIOL (Biological Study), USES (Uses), PREP (Preparation). 27483-92-7 belongs to class piperidines, name is 2-(Chloromethyl)-1-methylpiperidine hydrochloride, and the molecular formula is C7H15Cl2N, Application In Synthesis of 27483-92-7.

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

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

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