Category: 39546-32-2

Bian, Qiang published the artcileDesign, Synthesis, and Fungicidal Activities of Novel Piperidyl Thiazole Derivatives Containing Oxime Ether or Oxime Ester Moieties, Synthetic Route of 39546-32-2, the publication is Journal of Agricultural and Food Chemistry (2021), 69(13), 3848-3858, database is CAplus and MEDLINE.

To explore the influence of the positions of the two nitrogen atoms on the thiazole ring and the isoxazoline ring on the activity, a series of novel piperidyl thiazole derivatives containing oxime ether and oxime ester moieties with two nitrogen atoms on the same or opposite sides have been designed, synthesized, and first evaluated for their fungicidal activities against Phytophthora capsiciin vitro. The bioassay results showed that the target compounds possessed moderate to good fungicidal activities against P. capsici, among which oxime ether compound I shows the highest fungicidal activity in vitro (EC₅₀ = 0.0104μg/mL) which is higher than dimethomorph (EC₅₀ = 0.1148μg/mL) and diacetylenyl amide (EC₅₀ = 0.040μg/mL). Compared with oxime ether compounds (the two nitrogen atoms are on the opposite sides), the activities of oxime ester compounds were significantly reduced. It is different from the com. fungicide fluoxapiprolin, and the activities of the compounds with the two nitrogen atoms on the same side were significantly reduced compared to the compounds with the two nitrogen atoms on the opposite sides. Moreover, some compounds showed moderate to good antifungal activities in vivo against Phytophthora capsici, Pseudoperonospora cubensis, and Phytophthora infestans. SEM of compound I on the hyphae morphol. showed that compound I might cause mycelial abnormalities of P. capsici.

Journal of Agricultural and Food 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

Wang, Guo-Ming published the artcileThe inorganic-organic hybrid zinc phosphite poly[(μ₃-hydrogen phosphito-κ³O:O’:O”)(piperidin-1-ium-4-carboxylate-κO)zinc(II)], Application of Piperidine-4-carboxamide, the publication is Acta Crystallographica, Section C: Structural Chemistry (2014), 70(3), 289-291, database is CAplus and MEDLINE.

A new inorganic-organic hybrid zinc phosphite, [Zn(HPO₃)(C₆H₁₁NO₂)]_n, has been synthesized hydrothermally. Protonated piperidin-1-ium-4-carboxylate (PDCA) was generated in situ by hydrolysis of the piperidine-4-carboxamide precursor. The P atom possesses a typical PO₃H pseudo-pyramidal geometry. The crystal structure features an unusual (3,4)-connected two-dimensional inorganic zinc-phosphite layer, with organic PDCA ligands appended to the sheets and protruding into the interlayer region. Helical chains of opposite chirality are involved in the construction of a puckered sheet structure.

Acta Crystallographica, Section C: Structural 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 C11H16BNO3, Application of Piperidine-4-carboxamide.

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

Kitamura, Seiya published the artcileSulfur(VI) Fluoride Exchange (SuFEx)-Enabled High-Throughput Medicinal Chemistry, Formula: C6H12N2O, the publication is Journal of the American Chemical Society (2020), 142(25), 10899-10904, database is CAplus and MEDLINE.

Optimization of small-mol. probes or drugs is a synthetically lengthy, challenging, and resource-intensive process. Lack of automation and reliance on skilled medicinal chemists is cumbersome in both academic and industrial settings. Here, we demonstrate a high-throughput hit-to-lead process based on the biocompatible sulfur(VI) fluoride exchange (SuFEx) click chem. A high-throughput screening hit benzyl (cyanomethyl)carbamate (K_i = 8μM) against a bacterial cysteine protease SpeB was modified with a SuFExable iminosulfur oxydifluoride [RN=S(O)F₂] motif, rapidly diversified into 460 analogs in overnight reactions, and the products were directly screened to yield drug-like inhibitors with 480-fold higher potency (K_i = 18 nM). We showed that the improved mol. is active in a bacteria-host coculture. Since this SuFEx linkage reaction succeeds on picomole scale for direct screening, we anticipate our methodol. can accelerate the development of robust biol. probes and drug candidates.

Journal of the American Chemical Society 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, Formula: C6H12N2O.

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

Teramoto, Hiroyoshi published the artcileDesign and synthesis of a piperidinone scaffold as an analgesic through kappa-opioid receptor: Structure-activity relationship study of matrine alkaloids, Recommanded Product: Piperidine-4-carboxamide, the publication is Chemical & Pharmaceutical Bulletin (2016), 64(5), 410-419, database is CAplus and MEDLINE.

The matrine-type alkaloid 4-dimethylamino-1-pentanoylpiperidine (I) has an antinociceptive effect through its impact on the κ-opioid receptor (KOR). Derivatives of I were synthesized by altering its amide and tertiary amine groups; and they were evaluated for their antinociceptive effects. The results indicated that the distance between these groups on I was optimal for the antinociceptive effect. The effects obtained with racemic compounds II [R = β-CH₂Ph, α-CH₂Ph, R¹ = α-H, R² = R³ = H; R = β-CH₂Ph, α-CH₂Ph, R¹ = α-H, R² = (CH₂)₄Me, R³ = H; R = H, R¹ = α-H, β-H, R² = H, R³ = β-CH₂Ph; R = H, R¹ = α-H, β-H, R² = (CH₂)₄Me, R³ = β-CH₂Ph] and (-)-II [R = β-CH₂Ph, R¹ = β-H, R² = H, (CH₂)₄Me, R³ = H] indicated that the relative configuration of the 3- and 4-substituents influenced the effect mediated through the KOR.

Chemical & Pharmaceutical Bulletin 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 C18H28B2O4, Recommanded Product: Piperidine-4-carboxamide.

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

Song, Mingxia published the artcileDesign, synthesis, and anticonvulsant effects evaluation of nonimidazole histamine H₃ receptor antagonists/inverse agonists containing triazole moiety, Quality Control of 39546-32-2, the publication is Journal of Enzyme Inhibition and Medicinal Chemistry (2020), 35(1), 1310-1321, database is CAplus and MEDLINE.

Histamine H₃ receptors (H₃R) antagonists/inverse agonists are becoming a promising therapeutic approach for epilepsy. In this article, novel nonimidazole H₃R antagonists/inverse agonists have been designed and synthesized via hybriding the H₃R pharmacophore (aliphatic amine with propyloxy chain) with the 1,2,4-triazole moiety as anticonvulsant drugs. The majority of antagonists/inverse agonists prepared here exerted moderate to robust activities in cAMP-response element (CRE) luciferase screening assay. 1-(3-(4-(3-Phenyl-4H-1,2,4-triazol-4-yl)phenoxy)propyl)piperidine () and 1-(3-(4-(3-(4-chlorophenyl)-4H-1,2,4-triazol-4-yl)phenoxy)propyl)piperidine displayed the highest H₃R antagonistic activities, with IC₅₀ values of 7.81 and 5.92 nM, resp. Meanwhile, the compounds with higher H₃R antagonistic activities exhibited protection for mice in maximal electroshock seizure (MES)-induced convulsant model. Moreover, the protection of against the MES induced seizures was fully abrogated when mice were co-treated with RAMH, a CNS-penetrant H₃R agonist, which suggested that the potential therapeutic effect of was through H₃R. These results indicate that the attempt to find new anticonvulsant among H₃R antagonists/inverse agonists is practicable.

Journal of Enzyme Inhibition and 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 C12H17NS2, Quality Control of 39546-32-2.

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

Guo, Yan published the artcileDesign, synthesis, and evaluation of acetylcholinesterase and butyrylcholinesterase dual-target inhibitors against Alzheimer’s disease, Quality Control of 39546-32-2, the publication is Molecules (2020), 25(3), 489, database is CAplus and MEDLINE.

A series of novel derivatives based on G801-0274 were synthesized and evaluated, together with the known analogs, for their inhibitory activities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The inhibitory activities of AChE and BChE were evaluated in vitro by Ellman method. The results show that some compounds have good inhibitory activity against AChE and BChE. Among them, compound -N-((1-Benzylpiperidin-4-yl)methyl)-2-Oxoindoline-5-carboxamide showed the strongest inhibitory effect on both AChE (AChE IC₅₀ = 0.39μM) and BChE (BChE IC₅₀ = 0.28μM). Enzyme inhibition kinetics and mol. modeling studies have shown that the above compound bind simultaneously to the peripheral anionic site (PAS) and the catalytic sites (CAS) of AChE and BChE and in addition, the cytotoxicity of this compound is lower than that of Tacrine, indicating its suitability as anti-Alzheimer’s disease (anti-AD) agents. In summary, these data suggest that compound N-((1-Benzylpiperidin-4-yl)methyl)-2-Oxoindoline-5-carboxamide is a promising multipotent agent for the treatment of AD.

Molecules 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

Voller, Jiri published the artcile6-Substituted purines as ROCK inhibitors with anti-metastatic activity, Safety of Piperidine-4-carboxamide, the publication is Bioorganic Chemistry (2019), 103005, database is CAplus and MEDLINE.

Rho-associated serine/threonine kinases (ROCKs) are principal regulators of the actin cytoskeleton that regulate the contractility, shape, motility, and invasion of cells. We explored the relationships between structure and anti-ROCK2 activity in a group of purine derivatives substituted at the C6 atom by piperidin-1-yl or azepan-1-yl groups. Structure-activity relationship (SAR) analyses suggested that anti-ROCK activity is retained, and may be further increased, by substitution of the parent compounds at the C2 atom or by expansion of the C6 side chain. These inhibitors of ROCK can reach effective concentrations within cells, as demonstrated by a decrease in phosphorylation of the ROCK target MLC, and by inhibition of the ROCK-dependent invasion of melanoma cells in the collagen matrix. Our study may be useful for further optimization of C6-substituted purine inhibitors of ROCKs and of other sensitive kinases identified by the screening of a broad panel of protein kinases.

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 C15H14Cl2S2, Safety of Piperidine-4-carboxamide.

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

Pu, Szu-Yuan published the artcileOptimization of Isothiazolo[4,3-b]pyridine-Based Inhibitors of Cyclin G Associated Kinase (GAK) with Broad-Spectrum Antiviral Activity, Recommanded Product: Piperidine-4-carboxamide, the publication is Journal of Medicinal Chemistry (2018), 61(14), 6178-6192, database is CAplus and MEDLINE.

There is an urgent need for strategies to combat dengue and other emerging viral infections. We reported that cyclin G-associated kinase (GAK), a cellular regulator of the clathrin-associated host adaptor proteins AP-1 and AP-2, regulates intracellular trafficking of multiple unrelated RNA viruses during early and late stages of the viral lifecycle. We also reported the discovery of potent, selective GAK inhibitors based on an isothiazolo[4,3-b]pyridine scaffold, albeit with moderate antiviral activity. Here, we describe our efforts leading to the discovery of novel isothiazolo[4,3-b]pyridines that maintain high GAK affinity and selectivity. These compounds demonstrate improved in vitro activity against dengue virus, including in human primary dendritic cells, and efficacy against the unrelated Ebola and chikungunya viruses. Moreover, inhibition of GAK activity was validated as an important mechanism of antiviral action of these compounds These findings demonstrate the potential utility of a GAK-targeted broad-spectrum approach for combating currently untreatable emerging viral infections.

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, Recommanded Product: Piperidine-4-carboxamide.

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

Lv, Kai published the artcileDesign, synthesis and anti-HBV activity of NVR3-778 derivatives, Name: Piperidine-4-carboxamide, the publication is Bioorganic Chemistry (2020), 103363, database is CAplus and MEDLINE.

NVR3-778, one of the most advanced capsid assembly modulators (CAMs), is currently in phase II clin. trial for the treatment of HBV infection. In this study, we reported the first structure optimization of NVR3-778. Compound 2d was found to exhibit more potent anti-HBV activity (IC₅₀: 0.25μM), lower cytotoxicity (CC₅₀: 10.68μM) and higher selectivity index (SI: 40.72) than NVR3-778 (IC₅₀: 0.33μM; CC₅₀: 5.14μM; SI: 18.36) in vitro, and also display similar inhibitory effect on the assembly of HBV capsids as NVR3-778. Mol. docking further suggested that compound 2d might form a stronger interaction with core protein. Moreover, compound 2d also showed acceptable pharmacokinetic profiles. Currently compound 2d was selected as a new lead for further modifications, and studies to determine the in vivo anti-HBV studies of 2d will begin soon.

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

Zhang, Hongbo published the artcileDiscovery of novel small-molecule inhibitors of PD-1/PD-L1 interaction via structural simplification strategy, Safety of Piperidine-4-carboxamide, the publication is Molecules (2021), 26(11), 3347, database is CAplus and MEDLINE.

Blockade of the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction is currently the focus in the field of cancer immunotherapy, and so far, several monoclonal antibodies (mAbs) have achieved encouraging outcomes in cancer treatment. Despite this achievement, mAbs-based therapies are struggling with limitations including poor tissue and tumor penetration, long half-life time, poor oral bioavailability, and expensive production costs, which prompted a shift towards the development of the small-mol. inhibitors of PD-1/PD-L1 pathways. Even though many small-mol. inhibitors targeting PD-1/PD-L1 interaction have been reported, their development lags behind the corresponding mAb, partly due to the challenges of developing drug-like small mols. Herein, we report the discovery of a series of novel inhibitors targeting PD-1/PD-L1 interaction via structural simplification strategy by using BMS-1058 as a starting point. Among them, compound A9 stands out as the most promising candidate with excellent PD-L1 inhibitory activity (IC₅₀ = 0.93 nM, LE = 0.43) and high binding affinity to hPD-L1 (K_D = 3.64 nM, LE = 0.40). Furthermore, A9 can significantly promote the production of IFN-γ in a dose-dependent manner by rescuing PD-L1 mediated T-cell inhibition in Hep3B/OS-8/hPD-L1 and CD3-pos. T cells co-culture assay. Taken together, these results suggest that A9 is a promising inhibitor of PD-1/PD-L1 interaction and is worthy for further study.

Molecules 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 C11H24O3, Safety of Piperidine-4-carboxamide.

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