Category: 39546-32-2

Bogolubsky, Andrey V. published the artcileBis(2,2,2-trifluoroethyl) Carbonate as a Condensing Agent in One-Pot Parallel Synthesis of Unsymmetrical Aliphatic Ureas, Name: Piperidine-4-carboxamide, the publication is ACS Combinatorial Science (2014), 16(6), 303-308, database is CAplus and MEDLINE.

One-pot parallel synthesis of unsym. aliphatic ureas was achieved with bis(2,2,2-trifluoroethyl) carbonate. The procedure worked well for both the monosubstituted and functionalized alkylamines and required no special conditions (temperature control, order, or rate of addition). Thus, an acetonitrile solution of the first alkylamine, N,N-diisopropylethylamine, and bis(2,2,2-trifluoroethyl) carbonate was heated at 75 °C in a sealed tube for 2 h. After complete removal of bis(2,2,2-trifluoroethyl) carbonate and addition of DBU, the second alkylaminewas added to the crude trifluoroethyl carbamate to give the unsym. aliphatic urea. A library of 96 diverse ureas was easily synthesized.

ACS Combinatorial Science published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Name: Piperidine-4-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Powell, Jonathan published the artcileSmall Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor Activity with Immune Modulation through Reduction of Transforming Growth Factor Beta (TGFβ) Production in Regulatory T-Cells, Computed Properties of 39546-32-2, the publication is Journal of Medicinal Chemistry (2018), 61(9), 4135-4154, database is CAplus and MEDLINE.

We report the design, synthesis and comprehensive biol. evaluation of a range of some potent small-mol. neuropilin-1 (NRP1) antagonists. NRP1 is implicated in the immune response to tumors, particularly in Treg cell fragility, required for PD1 checkpoint blockade. The design of these compounds was based on a previously identified compound EG00229 which was used a starting point for optimization. Through targeting of specific amino-acid residues addnl. H-bonding interactions were introduced, which led to increases in binding affinity and potency. The design of these mols. was informed and supported by X-ray crystal structures. Pharmacokinetic data was obtained for some of the most potent compounds, and compound 1 (EG01377) was identified as having properties suitable for further investigation. Compound 1 was then tested in several in vitro assays, and was shown to have anti-angiogenic, anti-migratory and anti-tumor effects. Remarkably, 1 was shown to be selective for NRP1 over the closely related protein NRP2. In purified Nrp1+, FoxP3+, CD25+ populations of Tregs from mice 1 was able to block a glioma conditioned medium induced increase in TGFβ production This study therefore represents a comprehensive characterization of a small-mol. NRP1 antagonist, and provides the basis for future in vivo studies.

Journal of Medicinal Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Computed Properties of 39546-32-2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Bellale, Eknath published the artcileDiarylthiazole: an antimycobacterial scaffold potentially targeting PrrB-PrrA two-component system, Name: Piperidine-4-carboxamide, the publication is Journal of Medicinal Chemistry (2014), 57(15), 6572-6582, database is CAplus and MEDLINE.

Diarylthiazole (DAT), a hit from diversity screening, was found to have potent antimycobacterial activity against Mycobacterium tuberculosis (Mtb). In a systematic medicinal chem. exploration, the authors demonstrated chem. opportunities to optimize the potency and physicochem. properties. The effort led to more than 10 compounds with submicromolar MICs and desirable physicochem. properties. The potent antimycobacterial activity, in conjunction with low mol. weight, made the series an attractive lead (antibacterial ligand efficiency (ALE) >0.4). The series exhibited excellent bactericidal activity and was active against drug-sensitive and resistant Mtb. Mutational anal. showed that mutations in prrB impart resistance to DAT compounds but not to reference drugs tested. The sensor kinase PrrB belongs to the PrrBA two component system and is potentially the target for DAT. PrrBA is a conserved, essential regulatory mechanism in Mtb and has been shown to have a role in virulence and metabolic adaptation to stress. Hence, DATs provide an opportunity to understand a completely new target system for antimycobacterial drug discovery.

Journal of Medicinal Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Name: Piperidine-4-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Shidore, Mahesh published the artcileBenzylpiperidine-Linked Diarylthiazoles as Potential Anti-Alzheimer’s Agents: Synthesis and Biological Evaluation, HPLC of Formula: 39546-32-2, the publication is Journal of Medicinal Chemistry (2016), 59(12), 5823-5846, database is CAplus and MEDLINE.

A novel series of hybrid mols. were designed and synthesized by fusing the pharmacophoric features of cholinesterase inhibitor donepezil and diarylthiazole as potential multitarget-directed ligands for the treatment of Alzheimer’s disease (AD). The compounds showed significant in vitro anticholinesterase (anti-ChE) activity, the most potent compound I among them showing the highest activity (IC₅₀ value of 0.30 ± 0.01 μM) for AChE and (1.84 ± 0.03 μM) for BuChE. Compound I showed mixed inhibition of AChE in the enzyme kinetic studies. Some compounds exhibited moderate to high inhibition of AChE-induced Aβ_1-42 aggregation and noticeable in vitro antioxidant and antiapoptotic properties. Compound I showed significant in vivo anti-ChE and antioxidant activities. Furthermore, compound I demonstrated in vivo neuroprotection by decreasing Aβ_1-42-induced toxicity by attenuating abnormal levels of Aβ_1-42, p-Tau, cleaved caspase-3, and cleaved PARP proteins. Compound I exhibited good oral absorption and was well tolerated up to 2000 mg/kg, po, dose without showing toxic effects.

Journal of Medicinal Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C8H8O3, HPLC of Formula: 39546-32-2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

de Andrade, Peterson published the artcileHighly potent and selective aryl-1,2,3-triazolyl benzylpiperidine inhibitors toward butyrylcholinesterase in Alzheimer’s disease, Synthetic Route of 39546-32-2, the publication is Bioorganic & Medicinal Chemistry (2019), 27(6), 931-943, database is CAplus and MEDLINE.

Acetylcholinesterase (AChE) is the key enzyme targeted in Alzheimer’s disease (AD) therapy, nevertheless butyrylcholinesterase (BuChE) has been drawing attention due to its role in the disease progression. Thus, we aimed to synthesize novel cholinesterases inhibitors considering structural differences in their peripheral site, exploiting a moiety replacement approach based on the potent and selective hAChE drug donepezil. Hence, two small series of N-benzylpiperidine based compounds have successfully been synthesized as novel potent and selective hBuChE inhibitors. The most promising compounds (9(I) and 11(II)) were not cytotoxic and their kinetic study accounted for dual binding site mode of interaction, which is in agreement with further docking and mol. dynamics studies. Therefore, this study demonstrates how our strategy enabled the discovery of novel promising and privileged structures. Remarkably, II proved to be one of the most potent (0.17 nM) and selective (>58,000-fold) hBuChE inhibitor ever reported.

Bioorganic & Medicinal Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Synthetic Route of 39546-32-2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Chen, Feng published the artcileHydrogenation of Pyridines Using a Nitrogen-Modified Titania-Supported Cobalt Catalyst, Category: piperidines, the publication is Angewandte Chemie, International Edition (2018), 57(44), 14488-14492, database is CAplus and MEDLINE.

Heterogeneous recyclable catalysts were prepared by pyrolysis of Co(OAc)₂, melamine, and titanium dioxide; in their presence, pyridines underwent chemoselective hydrogenation to piperidines in water under acid-free conditions. The resulting materials show an unusual nitrogen-modified titanium structure through partial incorporation of nitrogen into the support. The catalyst was also used for the preparation of N-isopropylpiperidines by hydrogenation of pyridines in isopropanol.

Angewandte Chemie, International Edition published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Category: piperidines.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Karaluka, Valerija published the artcileB(OCH₂CF₃)₃-mediated direct amidation of pharmaceutically relevant building blocks in cyclopentyl methyl ether, Quality Control of 39546-32-2, the publication is Organic & Biomolecular Chemistry (2015), 13(44), 10888-10894, database is CAplus and MEDLINE.

The use of B(OCH₂CF₃)₃ for mediating direct amidation reactions of a wide range of pharmaceutically relevant carboxylic acids and amines is described, including numerous heterocycle-containing examples. An initial screen of solvents for the direct amidation reaction suggested that cyclopentyl Me ether, a solvent with a very good safety profile suitable for use over a wide temperature range, was an excellent replacement for the previously used solvent acetonitrile. Under these conditions amides could be prepared from 18 of the 21 carboxylic acids and 18 of the 21 amines examined Further optimization of one of the low yielding amidation reactions (36% yield) via a design of experiments approach enabled an 84% yield of the amide to be obtained.

Organic & Biomolecular Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Quality Control of 39546-32-2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Kuehl, Nikos published the artcileBeyond Basicity: Discovery of Nonbasic DENV-2 Protease Inhibitors with Potent Activity in Cell Culture, Quality Control of 39546-32-2, the publication is Journal of Medicinal Chemistry (2021), 64(8), 4567-4587, database is CAplus and MEDLINE.

The viral serine protease NS2B-NS3 is one of the promising targets for drug discovery against dengue virus and other flaviviruses. The mol. recognition preferences of the protease favor basic, pos. charged moieties as substrates and inhibitors, which leads to pharmacokinetic liabilities and off-target interactions with host proteases such as thrombin. We here present the results of efforts that were aimed specifically at the discovery and development of noncharged, small-mol. inhibitors of the flaviviral proteases. A key factor in the discovery of these compounds was a cellular reporter gene assay for the dengue protease, the DENV2proHeLa system. Extensive structure-activity relationship explorations resulted in novel benzamide derivatives with submicromolar activities in viral replication assays (EC₅₀ 0.24μM), selectivity against off-target proteases, and negligible cytotoxicity. This structural class has increased drug-likeness compared to most of the previously published active-site-directed flaviviral protease inhibitors and includes promising candidates for further preclin. development.

Journal of Medicinal Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Quality Control of 39546-32-2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Ji, Qinggang published the artcileDesign, synthesis and biological evaluation of novel diazaspirodecanone derivatives containing piperidine-4-carboxamide as chitin synthase inhibitors and antifungal agents, Name: Piperidine-4-carboxamide, the publication is Bioorganic Chemistry (2021), 105108, database is CAplus and MEDLINE.

A series of novel 2-oxo-(1-oxo-2,8-diazaspiro[4.5]decane-8-yl)ethylpiperidine carboxamide derivatives were designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS spectroscopy. All eighteen newly prepared compounds were evaluated for their inhibition against chitin synthase (CHS) and antifungal activities in vitro. The enzyme assay revealed that compound 5h showed excellent inhibitory activity against CHS with IC50 value of 0.10 mM, and the compounds 5b, 5d and 5q showed good inhibition against chitin synthase with IC50 values of 0.13 mM, 0.18 mM and 0.15 mM, resp., while IC50 value of ployoxin B was 0.08 mM. Meanwhile, the others of these compounds exhibited moderate inhibition potency against chitin synthase. The antifungal assay showed compound 5h had excellent antifungal activity compared with the control drugs fluconazole and polyoxin B against these tested strains including C. albicans, A. fumigatus, C. neoformans and A. flavus. Its excellent antifungal activity was consistent with its excellent chitin synthase inhibition. Compound 5k and 5l against C. albicans were comparable with fluconazole, and they showed strong antifungal potency against A. flavus with MIC values of 0.07 mmol/L and 0.13 mmol/L resp. Compound 5m had similar MIC value against A. fumigatus to fluconazole. The phenomenon that compounds 5b, 5d and 5q that showed good enzymic inhibition didnt exert good antifungal activity, while compounds 5k, 5l and 5m that showed moderate chitin synthase inhibition exhibited excellent antifungal activity was discussed. Furthermore, the trial of drug combination showed that compounds had synergistic effects or additive effects with fluconazole against tested fungi which also verified that these designed compounds targeted different targets from that of fluconazole. Addnl., the antibacterial trial showed that all synthesized compounds had little potency against tested bacteria strains. These results indicated that the designed compounds were potential chitin synthase inhibitors and had selectively antifungal activities.

Bioorganic Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Name: Piperidine-4-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Kosak, Urban published the artcileN-Propargylpiperidines with naphthalene-2-carboxamide or naphthalene-2-sulfonamide moieties: Potential multifunctional anti-Alzheimer’s agents, Name: Piperidine-4-carboxamide, the publication is Bioorganic & Medicinal Chemistry (2017), 25(2), 633-645, database is CAplus and MEDLINE.

In the brains of patients with Alzheimer’s disease, the enzymic activities of butyrylcholinesterase (BChE) and monoamine oxidase B (MAO-B) are increased. While BChE is a viable therapeutic target for alleviation of symptoms caused by cholinergic hypofunction, MAO-B is a potential therapeutic target for prevention of neurodegeneration in Alzheimer’s disease. Starting with piperidine-based selective human (h)BChE inhibitors and propargylamine-based MAO inhibitors, the authors have designed, synthesized and biochem. evaluated a series of N-propargylpiperidines. All of these compounds inhibited hBChE with good selectivity over the related enzyme, acetylcholinesterase, and crossed the blood-brain barrier in a parallel artificial membrane permeation assay. The crystal structure of one of the inhibitors (compound 3) in complex with hBChE revealed its binding mode. Three compounds (4, 5, and 6) showed concomitant inhibition of MAO-B. Addnl., the most potent hBChE inhibitor 7 and dual BChE and MAO-B inhibitor 6 were non-cytotoxic and protected neuronal SH-SY5Y cells from toxic amyloid β-peptide species.

Bioorganic & Medicinal Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Name: Piperidine-4-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem