Heterocyclic Building Blocks-piperidine

Wang, Wentao published the artcileTumor-targeting multi-shelled hollow nanospheres as drug loading platforms for imaging-guided combinational cancer therapy, Synthetic Route of 826-36-8, the publication is Biomaterials Science (2020), 8(6), 1748-1758, database is CAplus and MEDLINE.

In this work, we developed multi-shelled hollow nanospheres [RGD@a_m-ZnO@CuO@Au@DOX HNSs] as multifunctional therapeutic agents to achieve effective and targeted Zn²⁺/Cu²⁺ therapy, induced drug delivery under low pH/red-light conditions, and enhanced phototherapy under single red-light. The photothermal and photodynamic performance of a_m-ZnO@CuO@Au HNSs was enhanced relative to that of a_m-ZnO nanoparticles (NPs) or a_m-ZnO@CuO HNSs by utilizing the resonance energy transfer process and broad red-light absorption. The pH-sensitive a_m-ZnO@CuO@Au HNSs were dissolved to Zn²⁺/Cu²⁺ in the acidic endosomes/lysosomes of cancer cells, resulting in a cancer cell killing effect. The release performance of doxorubicin (DOX) from RGD@a_m-ZnO@CuO@Au@DOX HNSs was evaluated under low pH and red-light-irradiated conditions, and targeting of HNSs was confirmed by dual-modal imaging (magnetic resonance/fluorescence) of the tumor area. Moreover, in vivo synergistic therapy using RGD@a_m-ZnO@CuO@Au@DOX HNSs was further evaluated in mice bearing human pulmonary adenocarcinoma (A549) cells, achieving a remarkable synergistic antitumor effect superior to that obtained by monotherapy. This study validated that RGD@a_m-ZnO@CuO@Au@DOX HNSs can be a promising candidate for efficient postoperative cancer therapy.

Biomaterials Science published new progress about 826-36-8. 826-36-8 belongs to piperidines, auxiliary class Natural product, name is 2,2,6,6-Tetramethylpiperidin-4-one, and the molecular formula is C2H4ClNO, Synthetic Route of 826-36-8.

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

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

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

Tang, Kai published the artcileStructure-based design, synthesis and biological evaluation of aminopyrazines as highly potent, selective, and cellularly active allosteric SHP2 inhibitors, Computed Properties of 39546-32-2, the publication is European Journal of Medicinal Chemistry (2022), 114106, database is CAplus and MEDLINE.

Src homol.-2-containing protein tyrosine phosphatase 2 (SHP2) encoded by the proto-oncogene PTPN11 is the first identified non-receptor protein tyrosine phosphatase. SHP2 dysregulation contributes to the pathogenesis of different cancers, making SHP2 a promising therapeutic target for cancer therapy. In this article, authors report the structure-guided design based on the well-characterized SHP2 inhibitor SHP099, extensive structure-activity relationship studies (SARs) of aminopyrazines, biochem. characterization and cellular potency. These medicinal chem. efforts lead to the discovery of the lead compound TK-453 I, which potently inhibits SHP2 (SHP2WT IC₅₀ = 0.023μM, ΔTm = 7.01°C) in a reversible and noncompetitive manner. Compound I exhibits high selectivity over SHP2PTP, SHP1 and PTP1B, and may bind at the “tunnel” allosteric site of SHP2 as SHP099. As the key pharmacophore, the aminopyrazine scaffold not only reorganizes the cationic-π stacking interaction with R111 via the novel hydrogen bond interaction between the S atom of thioether linker and T219, but also mediates a hydrogen bond with E250. In vitro studies indicate that I inhibits proliferation of HeLa, KYSE-70 and THP-1 cells moderately and induces apoptosis of Hela cells. Further mechanistic studies suggest that I can decrease the phosphorylation levels of AKT and Erk1/2 in HeLa and KYSE-70 cells.

European 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 C7H13BN2O2, Computed Properties of 39546-32-2.

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

Xin, Zhili published the artcileDiscovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors, Quality Control of 1032229-33-6, the publication is Bioorganic & Medicinal Chemistry Letters (2008), 18(15), 4298-4302, database is CAplus and MEDLINE.

A series of structurally novel stearoyl-Co-A desaturase 1 (SCD1) inhibitors has been identified via mol. scaffold manipulation. Preliminary structure-activity relationship (SAR) studies led to the discovery of potent, and orally bioavailable piperidine-aryl urea-based SCD1 inhibitors. 4-(2-Chlorophenoxy)-N-[3-(Me carbamoyl)phenyl]piperidine-1-carboxamide (I) exhibited robust in vivo activity with dose-dependent desaturation index lowering effects.

Bioorganic & Medicinal Chemistry Letters published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C9H21NO3, Quality Control of 1032229-33-6.

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

Liu, Jian-Guo published the artcileDevelopment of Bisindole-Substituted Aminopyrazoles as Novel GSK-3β Inhibitors with Suppressive Effects against Microglial Inflammation and Oxidative Neurotoxicity, Formula: C18H24N2O2, the publication is ACS Chemical Neuroscience (2020), 11(20), 3398-3408, database is CAplus and MEDLINE.

Development of glycogen synthase kinase-3β (GSK-3β) inactivation-centric agents with polypharmacol. profiles is increasingly recognized as a promising therapeutic strategy against the multifactorial etiopathol. of Alzheimer’s disease (AD). In this respect, a series of disubstituted aminopyrazole derivatives were designed and synthesized as a new class of GSK-3β inhibitors. Most of these derivatives possess GSK-3β inhibitory activities with IC₅₀ values in the micromolar ranges, among which bisindole-substituted aminopyrazole derivative 6h displayed moderate GSK-3β inhibition (IC₅₀ = 1.76 ± 0.19μM), and alleviative effects against lipopolysaccharide (LPS)-induced glial inflammation in BV-2 cells and glutamate-induced oxidative neurotoxicity in HT-22 cells. Further in vivo studies indicated that compound 6h(I) had potent anti-inflammatory effect, by showing markedly reduced microglial activation and astrocyte proliferation in the brain of LPS-injected mice. Overall, the simultaneous modulation of 6h on multiple dysfunctions of disease network highlights this structural distinctively bisindole-substituted aminopyrazole could be a useful prototype for the discovery of novel therapeutic agents to tackle AD and other GSK-3β associated complex neurol. syndromes.

ACS Chemical Neuroscience published new progress about 170364-89-3. 170364-89-3 belongs to piperidines, auxiliary class Indole,Piperidine,Amide, name is tert-Butyl 4-(1H-indol-1-yl)piperidine-1-carboxylate, and the molecular formula is C18H24N2O2, Formula: C18H24N2O2.

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

Wu, Qi-Fan published the artcileDesign, synthesis and fungicidal activity of isothiazole-thiazole derivatives, Related Products of piperidines, the publication is RSC Advances (2018), 8(69), 39593-39601, database is CAplus and MEDLINE.

3,4-Dichloroisothiazoles can induce systemic acquired resistance (SAR) to enhance plant resistance against a subsequent pathogen attack, and oxathiapiprolin exhibits excellent anti-fungal activity against oomycetes targeting at the oxysterol-binding protein. To discover novel chems. with systemic acquired resistance and fungicidal activity, 21 novel isothiazole-thiazole derivatives were designed, synthesized and characterized according to the active compound derivatization method. Compound 6u, with EC₅₀ values of 0.046 mg L^-1 and 0.20 mg L^-1 against Pseudoperonospora cubensis (Berk. et Curt.) Rostov and Phytophthora infestans in vivo, might act at the same target as oxysterol binding protein (PcORP1) of oxathiapiprolin; this result was validated by cross-resistance and mol. docking studies. The expression of the systemic acquired resistance gene pr1 was significantly up-regulated after treating with compound 6u for 24 h (43-fold) and 48 h (122-fold). These results can help the development of isothiazole-thiazole-based novel fungicides.

RSC Advances 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 C19H22BNO5, Related Products of piperidines.

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

Wu, Qifan published the artcileDiscovery of Novel Piperidinylthiazole Derivatives As Broad-Spectrum Fungicidal Candidates, Category: piperidines, the publication is Journal of Agricultural and Food Chemistry (2019), 67(5), 1360-1370, database is CAplus and MEDLINE.

Oxathiapiprolin is one of the best active fungicides discovered for oomycetes control. To develop a fungicide candidate with a broad spectrum of activity, 22 new piperidinylthiazole derivatives were designed and synthesized. Compound (I) showed the best activity against Pseudoperonospora cubensis (Berk. et Curt.) Rostov and Phytophthora infestans in vivo with 100% and 80% of inhibition, resp., at 1 mg/L, and 72.87% of field efficacy against P. cubensis at 1 g ai/667 m² validated these results. Compound (II) exhibited a broad spectrum of excellent activity against Sclerotinia sclerotiorum with EC₅₀ = 0.30 mg/L (>10 times more active than oxathiapiprolin and azoxystrobin in vitro), good activity against Botrytis cinerea, Cercospora arachidicola, and Gibberella zeae with EC₅₀ of 14.54, 5.57, and 14.03 mg/L in vitro and against P. cubensis and P. infestans with 60% and 30% inhibition rates, resp., at 1 mg/L in vivo. Mode of action studies by RNA sequencing anal. discovered oxysterol-binding protein (OSBP), chitin synthase (CHS1), and (1,3)-β-glucan synthase (FKS2) as the potent target of II against S. sclerotiorum. Quenching studies validated that OSBP was the same target of both II and oxathiapiprolin; it was quenched by both of them. Our studies discovered isothiazole-containing piperidinylthiazole as an OSBP target-based novel lead for fungicide development.

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 C11H8O3, Category: piperidines.

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

Cai, Dong published the artcileExploring new structural features of the 18β-glycyrrhetinic acid scaffold for the inhibition of anaplastic lymphoma kinase, Application of Piperidine-4-carboxamide, the publication is Molecules (2019), 24(19), 3631pp., database is CAplus and MEDLINE.

Novel 18β-glycyrrhetinic acid derivatives possessing a carbamate moiety I [R = 4-ClC₆H₄, 3,4-di-ClC₆H₃, 4-Cl-3-CF₃C₆H₃, etc.; R¹ = OH, morpholino] and structurally similar ester derivatives II [R² = 4-ClC₆H₄CH₂, (4-methylpiperazin-1-yl)methyl, (4-formyl-1-piperidyl)methyl, etc.] were developed and evaluated for their efficacy as antitumor inhibitors. In the cellular assays, most of the N-substituted carbamate derivatives I at the C3-position exhibited potent activities. The results of SAR investigation revealed that the introduction of the morpholine group at the C30-COOH led to a significant loss of the inhibitory potency. Among the ester derivatives, the ester group at C3-position also determined a noticeable reduction in the efficacy. Compound I [R = 3-CF₃C₆H₄; R¹ = OH] exhibited the most prominent antiproliferative activity against six human cancer cells (A549, HT29, HepG2, MCF-7, PC-3, and Karpas299). Furthermore, compound I [R = 3-CF₃C₆H₄; R¹ = OH] exerted a moderate inhibiting effect on the ALK. The results of mol. docking analyses suggested that it could bind well to the active site of the receptor ALK, which was consistent with the biol. data. These results might inspire further structural optimization of 18β-glycyrrhetinic acid aiming at the development of potent antitumor agents. The structures I [R = 4-ClC₆H₄, 4-BrC₆H₄, 4-FC₆H₄, 3-CF₃C₆H₄, 4-CF₃OC₆H₄; R¹ = morpholino] were studied by X-ray crystallog. analyses.

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, Application of Piperidine-4-carboxamide.

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