Day: November 16, 2022

Wei, Huiqiang published the artcileNovel PHD2/HDACs hybrid inhibitors protect against cisplatin-induced acute kidney injury, Quality Control of 73874-95-0, the main research area is hydroxypyrazolyl pyrimidinecarbonylamine preparation PHD2 HDAC inhibitor acute kidney injury; Acute kidney injury; HDACs; Hybrid inhibitor; PHD2; Renal protecting.

Acute kidney injury (AKI) is associated with high morbidity and mortality. Cisplatin is a common chemotherapeutic, but its nephrotoxicity-driven AKI limits its clin. application. Currently, there are no specific and satisfactory therapies in the clinic for AKI. Inhibitors of hypoxia-inducible factor prolyl hydroxylase 2 (HIF-PHD2) or histone deacetylase (HDACs) had shown renoprotective effects against AKI in preclin. studies. This study aimed to develop a novel therapeutic to prevent AKI progression by targeting PHD2 and HDACs simultaneously. We designed and synthesized a series of PHD2/HDACs hybrid inhibitors. The initial drug activity screening identified a candidate compound 2-{4-[(4-Hydroxy-2-pyrazol-1-yl-pyrimidine-5-carbonyl)amino]-piperidin-1-yl}-N-hydroxy-pyrimidine-5-carboxylamide, which exhibited potent inhibitory activities against PHD2 and HDAC1/2/6. Cellular analyses further showed that 2-{4-[(4-Hydroxy-2-pyrazol-1-yl-pyrimidine-5-carbonyl)amino]-piperidin-1-yl}-N-hydroxy-pyrimidine-5-carboxylamide did not affect cisplatin′s antitumor activity in cancer cells but strongly protected cisplatin-induced toxicity on HK-2 cells. In vivo studies with the cisplatin-induced AKI mouse model demonstrated that 31c remarkably alleviated kidney dysfunction with suppressed plasma BUN/SCr and increased EPO levels. The potent renoprotective effects of 2-{4-[(4-Hydroxy-2-pyrazol-1-yl-pyrimidine-5-carbonyl)amino]-piperidin-1-yl}-N-hydroxy-pyrimidine-5-carboxylamide on AKI were confirmed by significant improvements in pathol. kidney conditions in the mouse model. These results suggest that the novel PHD2/HDACs hybrid inhibitor, 2-{4-[(4-Hydroxy-2-pyrazol-1-yl-pyrimidine-5-carbonyl)amino]-piperidin-1-yl}-N-hydroxy-pyrimidine-5-carboxylamide, has a clin. potential as the renoprotective agent for the treatment/prevention of cisplatin-induced AKI for various cancers.

European Journal of Medicinal Chemistry published new progress about Acute kidney injury. 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

Li, Jia published the artcileMetal-free aminohalogenation of quinones with alkylamines and NXS at room temperature, Computed Properties of 73874-95-0, the main research area is halo amino naphthalenedione preparation; naphthoquinone amine aminohalogenation; NXS; aminohalogenation; metal-free; quinones; radical reactions.

A simple and practical strategy for intermol. aminohalogenation of quinone with alkyl amines and NXS was developed for preparation of halo(amino)naphthalenediones I [X = H, Cl, Br, I; R1 = Me; R2 = 2-cyanoethyl, (4-bromophenyl)methyl, phenethyl, (3S)-3-(2-methylphenoxy)-3-phenyl-propyl; R1 = R2 = (CH2)2O(CH2)2, (CH2)2CH(OH)(CH2)2, (CH2)2CH(CO2Me)(CH2)2], in which haloamines generated in situ were employed as bifunctional reagents. The reaction system was reliable, efficient and wide in substrate range, which was suitable for the two-fold aminochlorination of 1, 4-benzoquinones, large-scale reaction and late-stage modification of pharmaceuticals.

Frontiers in Chemistry (Lausanne, Switzerland) published new progress about Halogenation (amino). 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

Reddy, G. Lakshma published the artcileDesign, synthesis and biological evaluation of pyrazolopyrimidinone based potent and selective PDE5 inhibitors for treatment of erectile dysfunction, Application In Synthesis of 73874-95-0, the main research area is pyrazolopyrimidinone PDE5 inhibitor erectile dysfunction; Erectile dysfunction; PDE5 inhibitors; PDE6 enzyme; Pyrazolopyrimidinone derivatives; Sildenafil.

The authors’ previous discovery of series of pyrazolopyrimidinone based PDE5 inhibitors led to find potent leads but with low aqueous solubility and poor bioavailability, and low selectivity. Now, a new series of same pyrazolopyrimidinone scaffold is designed, synthesized and evaluated for its PDE5 inhibitory potential. Some of the mols. are found more potent and selective PDE5 inhibitors in vitro than sildenafil. The studies revealed that compound 5 is 20 fold selective to PDE5 against PDE6. As PDE6 enzyme is involved in the phototransduction pathway in the retina and creates distortion problem, the selectivity for PDE5 specifically against PDE6 enzyme is preferred for any development candidate and in present study, compound 5 is devoid of this liability of selectivity issue. Moreover, compound 5 showed excellent in vivo efficacy in conscious rabbit model, it’s almost comparable to sildenafil. The preclin. pharmacol. including pharmacokinetic and physicochem. parameter studies were also performed for compound 5, it has good PK properties and other physicochem. parameters. The development of these selective PDE5 inhibitors can further lead to draw strategies for the novel preclin. and/or clin. candidates based on pyrazolopyrimidinone scaffold.

Bioorganic Chemistry published new progress about Erectile dysfunction. 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

Bengtsson, Christoffer published the artcileDesign of small molecule inhibitors of acetyl-CoA carboxylase 1 and 2 showing reduction of hepatic malonyl-CoA levels in vivo in obese Zucker rats, Category: piperidines, the main research area is preparation acetyl CoA carboxylase inhibitor quinoline.

Inhibition of acetyl-CoA carboxylases has the potential for modulating long chain fatty acid biosynthesis and mitochondrial fatty acid oxidation Hybridization of weak inhibitors of ACC2 provided a novel, moderately potent but lipophilic series. Optimization led to two compounds, which exhibit potent inhibition of human ACC2, 10-fold selectivity over inhibition of human ACC1, good phys. and in vitro ADME properties and good bioavailability. X-ray crystallog. has shown this series binding in the CT-domain of ACC2 and revealed two key hydrogen bonding interactions. Both most potent compounds lower levels of hepatic malonyl-CoA in vivo in obese Zucker rats.

Bioorganic & Medicinal Chemistry published new progress about Drug bioavailability. 132431-09-5 belongs to class piperidines, name is Benzyl (piperidin-4-ylmethyl)carbamate, and the molecular formula is C14H20N2O2, Category: piperidines.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Kirk, R. published the artcileRational design, synthesis and testing of novel tricyclic topoisomerase inhibitors for the treatment of bacterial infections part 2, Application In Synthesis of 73874-95-0, the main research area is tricyclic DNA gyrase topoisomerase inhibitor antibacterial agent pharmacokinetics.

Building on our previously-reported novel tricyclic topoisomerase inhibitors (NTTIs), we disclose the discovery of REDX07965, which has an MIC90 of 0.5 μg mL-1 against Staphylococcus aureus, favorable in vitro pharmacokinetic properties, selectivity vs. human topoisomerase II and an acceptable toxicity profile. The results herein validate a rational design approach to address the urgent unmet medical need for novel antibiotics.

RSC Medicinal Chemistry published new progress about Antibacterial agents. 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

Bhavanam, Lourdu Rani published the artcileSynthesis, Characterization, Anticancer and Antimicrobial Activity Studies of Novel Isomeric 2,4-Disubstituted Ureide Derivatives of Pyrimidinopiperidines, COA of Formula: C10H20N2O2, the main research area is pyrimidinopiperidine ureide preparation anticancer antimicrobial.

A series of isomeric ureide derivatives of novel 2,4-disubstituted pyrimidinopiperidines, e.g., I were synthesized starting from 2,4-dichloropyrimidine. All the final products were purified on silica and characterized by spectral anal. Both the 2,4-disubstituted pyrimidinopiperidines were analyzed for their in vitro anticancer activity on the cell lines HCT116, MIA-PaCa2 and MDA-MB 231 by using MTT cell proliferation assay. Further, the antimicrobial studies were carried out against different bacterial and fungal strains by employing cup plate method. These compounds showed significant anticancer activity on tested three cancer cell lines and exhibited potent antimicrobial activity in tested strains of bacteria and fungi.

ChemistrySelect published new progress about Antibacterial 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

Kamsani, Supriya published the artcileDesign and synthesis of novel Bis-morpholinotriazine analogs and their antibacterial, antifungal and antioxidant studies, Category: piperidines, the main research area is bismorpholino triazine preparation antibacterial antifungal antioxidant.

A series of novel analogs of bis-morpholino-1,3,5-triazine derivatives were synthesized from cyanuric chloride as starting precursor. The products were characterized by spectral data and their biol. evaluation against microbials were reported. Antioxidant properties of these compounds were also studied.

Asian Journal of Chemistry published new progress about Antibacterial 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

Beus, Maja published the artcileChloroquine fumardiamides as novel quorum sensing inhibitors, Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is Chromobacterium bactericidal quorum sensing primaquine cell communication; Chloroquine; Fumardiamide; Quinoline derivatives; Quorum quenching; Quorum sensing inhibition.

In our study, a set of twenty-six fumardiamides with a quinoline head-group were evaluated as potential QSIs. Two strains of Gram-neg. Chromobacterium violaceum (violacein-producing strain ATCC31532 and violacein-neg., mini-Tn5 mutant derivative CV026) were used as QS reporters for testing anti-QS and bactericidal activity of various quinoline fumardiamides. The initial screening of eighteen fumardiamides with primaquine, mefloquine and chloroquine scaffolds identified chloroquine derivatives as the most promising QSIs. Tail-group optimization of chloroquine fumardiamides led to the most active compounds 27, 29 and 30 bearing aminoethyl or piperidine moieties. At 400 μM concentration, these compounds inhibited the QS of C. violaceum strains in a manner similar to quercetin (the model QSI), while at the 40 μM concentration their inhibitory effect was twice less than that of quercetin. As none of the compounds displayed a bactericidal effect and that the QS inhibition was specific to the CV026 strain, our findings indicate that the structurally optimized chloroquine derivatives could function as quorum quenching (QQ) agents with a potential to block the signaling without entering the cell. In conclusion, our finding provides an important step toward the further design of agents targeting cell-to-cell communication.

Bioorganic & Medicinal Chemistry Letters published new progress about Antibacterial 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

Weinhart, Corinna. G. published the artcileDibenzodiazepinone-type muscarinic receptor antagonists conjugated to basic peptides: Impact of the linker moiety and unnatural amino acids on M2R selectivity, Application of tert-Butyl piperidin-4-ylcarbamate, the main research area is dibenzodiazepinone peptide synthesis muscarinic receptor antagonist mol docking; solid phase synthesis peptide coupling linker; Basic amino acid; Dibenzodiazepinone derivative; Induced-fit docking; M2R antagonist; M2R selectivity; MR subtype selectivity; Muscarinic acetylcholine receptors; Peptide.

The family of human muscarinic acetylcholine receptors (MRs) is characterized by a high sequence homol. among the five subtypes (M1R-M5R), being the reason for a lack of subtype selective MR ligands. In continuation of our work on dualsteric dibenzodiazepinone-type M2R antagonists, a series of M2R ligands containing a dibenzodiazepinone pharmacophore linked to small basic peptides was synthesized (64 compounds). The linker moiety was varied with respect to length, number of basic nitrogens (0-2) and flexibility. Besides proteinogenic basic amino acids (Lys, Arg), shorter homologues of Lys and Arg, containing three and two methylene groups, resp., as well as D-configured amino acids were incorporated. The type of linker had a marked impact on M2R affinity and also effected M2R selectivity. In contrast, the structure of the basic peptide rather determined M2R selectivity than M2R affinity. For example, the most M2R selective compound (UR-CG188) with picomolar M2R affinity (pKi 9.60), exhibited a higher M2R selectivity (ratio of Ki M1R/M2R/M3R/M4R/M5R: 110:1:5200:55:2300) compared to the vast majority of reported M2R preferring MR ligands. For selected ligands, M2R antagonism was confirmed in a M2R miniG protein recruitment assay.

European Journal of Medicinal Chemistry published new progress about Hamster cell line CHO. 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

Arranz-Gibert, Pol published the artcileLipid Bilayer Crossing-The Gate of Symmetry. Water-Soluble Phenylproline-Based Blood-Brain Barrier Shuttles, Quality Control of 158922-07-7, the main research area is lipid bilayer permeation drug delivery phenylproline blood brain barrier.

Drug delivery to the brain can be achieved by various means, including blood-brain barrier (BBB) disruption, neurosurgical-based approaches, and mol. design. Recently, passive diffusion BBB shuttles have been developed to transport low-mol.-weight drug candidates to the brain which would not be able to cross unaided. The low water solubility of these BBB shuttles has, however, prevented them from becoming a mainstream tool to deliver cargos across membranes. Here, we describe the design, synthesis, physicochem. characterization, and BBB-transport properties of phenylproline tetrapeptides, (PhPro)4, an improved class of BBB shuttles that operates via passive diffusion. These PhPro-based BBB shuttles showed 3 orders of magnitude improvement in water solubility compared to the gold-standard (N-MePhe)4, while retaining very high transport values. Transport capacity was confirmed when two therapeutically relevant cargos, nipecotic acid and L-3,4-dihydroxyphenylalanine (i.e., L-DOPA), were attached to the shuttle. Addnl., we used the unique chiral and conformationally restricted character of the (PhPro)4 shuttle to probe its chiral interactions with the lipid bilayer of the BBB. We studied the transport properties of 16 (PhPro)4 stereoisomers using the parallel artificial membrane permeability assay and looked at differences in secondary structure. Most stereoisomers displayed excellent transport values, yet this study also revealed pairs of enantiomers with high enantiomeric discrimination and different secondary structure, where one enantiomer maintained its high transport values while the other had significantly lower values, thereby confirming that stereochem. plays a significant role in passive diffusion. This could open the door to the design of chiral and membrane-specific shuttles with potential applications in cell labeling and oncol.

Journal of the American Chemical Society published new progress about Biological permeation. 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, Quality Control of 158922-07-7.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem