Category: 39546-32-2

Zhang, Xinyu published the artcile3,6-Diamino-7,8-dihydroisoquinoline-4-carbonitrile derivatives: unexpected facile synthesis, full-color-tunable solid-state emissions and mechanofluorochromic activities, Safety of Piperidine-4-carboxamide, the publication is Organic Chemistry Frontiers (2021), 8(5), 856-867, database is CAplus.

A series of novel 3,6-diamino-7,8-dihydroisoquinoline-4-carbonitrile (DDIC) derivatives I [R = Bn, R¹ = Me; R² = Ph, 4-FC₆H₄, 2-thienyl, etc.; RR¹ = (CH₂)₄, (CH₂)₅, (CH₂)₂CH(CH₃)(CH₂)₂, etc.] were prepared from dicyanomethylene-4H-pyran derivatives and secondary amines by a mechanism of ring-opening and sequential ring-closing reactions. This reaction had the advantages of readily available materials, simple operations, mild reaction conditions, a broad substrate scope and good yields. The DDIC derivatives displayed solid-state fluorescence with the emission wavelengths covering the whole visible light range and the solid-state emissions were demonstrated to be ascribed to the twisted mol. conformations and loose stacking modes by crystal structural anal. Among the compounds, 9aa exhibited a bathochromic mechanofluorochromic (MFC) phenomenon from blue to cyan due to increased mol. conjugation upon grinding, whereas 3aj and 3ka exhibited hypsochromic MFC activities with the color changing from orange to green and red to orange, resp., because of decreased mol. conjugation, revealing that full-color-tunable emissions could also be realized by mechanofluorochromism. Furthermore, MFC-active mols. could be used in the field of encryption of important image or text information. Addnl., 3ka was demonstrated to emit single-mol. white fluorescence in organic solvents through the regulation of the concentration The unexpected discovery of the DDIC derivatives provided a new possibility for the design and synthesis of novel isoquinoline-based fluorescent materials with excellent performance in the solid state.

Organic Chemistry Frontiers 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 C10H10O2, Safety of Piperidine-4-carboxamide.

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

Mao, Fei published the artcileDesign, Synthesis, and Biological Evaluation of Orally Available First-Generation Dual-Target Selective Inhibitors of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5) for the Treatment of Alzheimer’s Disease, Safety of Piperidine-4-carboxamide, the publication is ACS Chemical Neuroscience (2018), 9(2), 328-345, database is CAplus and MEDLINE.

Through drug discovery strategies of repurposing and redeveloping existing drugs, a series of novel tadalafil derivatives were rationally designed, synthesized, and evaluated to seek dual-target AChE/PDE5 inhibitors as good candidate drugs for Alzheimer’s disease (AD). Among these derivatives, (6R,12aR)-6-(benzo[d][1,3]dioxol-5-yl)-2-(2-(1-benzylpiperidin-4yl)ethyl)-2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dione (1p, I) and (6R,12aS)-6-(benzo[d][1,3]dioxol-5-yl)-2-(2-(1-benzylpiperidin-4yl)ethyl)-2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dione (1w, II) exhibited excellent selective dual-target AChE/PDE5 inhibitory activities and improved blood-brain barrier (BBB) penetrability. Importantly, II·Cit (citrate of II) could reverse the cognitive dysfunction of scopolamine-induced AD mice and exhibited an excellent effect on enhancing cAMP response element-binding protein (CREB) phosphorylation in vivo, a crucial factor in memory formation and synaptic plasticity. Moreover, the mol. docking simulations of II with hAChE and hPDE5A confirmed that the design strategy was rational. In summary, the research provides a potential selective dual-target AChE/PDE5 inhibitor as a good candidate drug for the treatment of AD, and it could also be regarded as a small mol. probe to validate the novel AD therapeutic approach in vivo.

ACS Chemical Neuroscience 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, Safety of Piperidine-4-carboxamide.

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

Peng, Hui published the artcileSuppression of NRF2-ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells, SDS of cas: 39546-32-2, the publication is Toxicology and Applied Pharmacology (2016), 1-7, database is CAplus and MEDLINE.

Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of the antioxidant response element (ARE)-dependent transcription, plays a pivotal role in chem. detoxification in normal and tumor cells. Consistent with previous findings that NRF2-ARE contributes to chemotherapeutic resistance of cancer cells, we found that stable knockdown of NRF2 by lentiviral shRNA in human acute monocytic leukemia (AML) THP-1 cells enhanced the cytotoxicity of several chemotherapeutic agents, including arsenic trioxide (As₂O₃), etoposide and doxorubicin. Using an ARE-luciferase reporter expressed in several human and mouse cells, we identified a set of compounds, including isonicotinic acid amides, isoniazid and ethionamide, that inhibited NRF2-ARE activity. Treatment of THP-1 cells with ethionamide, for instance, significantly reduced mRNA expression of multiple ARE-driven genes under either basal or As₂O₃-challenged conditions. As determined by cell viability and cell cycle, suppression of NRF2-ARE by ethionamide also significantly enhanced susceptibility of THP-1 and U937 cells to As₂O₃-induced cytotoxicity. In THP-1 cells, the sensitizing effect of ethionamide on As₂O₃-induced cytotoxicity was highly dependent on NRF2. To our knowledge, the present study is the first to demonstrate that ethionamide suppresses NRF2-ARE signaling and disrupts the transcriptional network of the antioxidant response in AML cells, leading to sensitization to chemotherapeutic agents.

Toxicology and Applied Pharmacology 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, SDS of cas: 39546-32-2.

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

Long, Jiao published the artcileNickel/Bronsted Acid-Catalyzed Chemo- and Enantioselective Intermolecular Hydroamination of Conjugated Dienes, Safety of Piperidine-4-carboxamide, the publication is iScience (2019), 369-379, database is CAplus and MEDLINE.

A novel nickel/Bronsted acid-catalyzed asym. hydroamination of acyclic 1,3-dienes was established. A wide array of primary and secondary amines were transformed into allylic amines with high yields and high enantioselectivities under very mild conditions. Moreover, this method was compatible with various functional groups and heterocycles, allowing for late-stage functionalization of biol. active complex mols. Remarkably, this protocol exhibited good chemoselectivity with respect to amines bearing two different nucleophilic sites. Mechanistic studies revealed that the enantioselective carbon-nitrogen bond-forming step was reversible.

iScience 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, Safety of Piperidine-4-carboxamide.

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

Wu, Chun-Feng published the artcileSynthesis and bioevaluation of diaryl urea derivatives as potential antitumor agents for the treatment of human colorectal cancer, HPLC of Formula: 39546-32-2, the publication is European Journal of Medicinal Chemistry (2022), 114055, database is CAplus and MEDLINE.

The development of inhibitors targeting the PI3K-Akt-mTOR signaling pathway has been greatly hindered by the on-target AEs, such as hyperglycemia and hepatotoxicities. In this study, a series of diaryl urea derivatives has been designed and synthesized based on clin. candidate gedatolisib, and most of the newly synthesized derivatives showed kinase inhibitory and antiproliferative activities within nanomolar and submicromolar level, resp. The terminal L-proline amide substituted derivative I showed 8.6-fold more potent PI3Kα inhibitory activity (0.7 nM) and 4.6-fold more potent antiproliferative effect against HCT116 cell lines (0.11μM) compared with control gedatolisib. The potential antitumor mechanism and efficacy of I in HCT116 xenograft models have also been evaluated, and found I showed comparable in vivo antitumor activity with gedatolisib. The safety investigations revealed that compound I exhibited more safer profiles in the selectivity of liver cells (selectivity index: >6.6 vs 1.85) and blood glucose regulation than gedatolisib. In addition, the in vitro stability assays also indicated that developed compound I possessed good metabolic stabilities.

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 C9H9BO2, HPLC of Formula: 39546-32-2.

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

Dong, Yuxiang published the artcileStructure-Activity Relationship of the Antimalarial Ozonide Artefenomel (OZ439), Quality Control of 39546-32-2, the publication is Journal of Medicinal Chemistry (2017), 60(7), 2654-2668, database is CAplus and MEDLINE.

Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with their higher pK_a and lower log D_7.4 values. For primary amino ozonides, addition of polar functional groups decreased in vivo antimalarial efficacy. For secondary amino ozonides, addnl. functional groups had variable effects on metabolic stability and efficacy, but the most effective members of this series also had the highest log D_7.4 values. For tertiary amino ozonides, addition of polar functional groups with H-bond donors increased metabolic stability but decreased in vivo antimalarial efficacy. Primary and tertiary amino ozonides with cycloalkyl and heterocycle substructures were superior to their acyclic counterparts. The high curative efficacy of these ozonides was most often associated with high and prolonged plasma exposure, but exposure on its own did not explain the presence or absence of either curative efficacy or in vivo toxicity.

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

Keita, Massaba published the artcileSynthesis of isocyanides through dehydration of formamides using XtalFluor-E, Synthetic Route of 39546-32-2, the publication is Tetrahedron Letters (2015), 56(2), 461-464, database is CAplus.

The formation of isocyanides from formamides using XtalFluor-E, [Et₂NSF₂]BF₄, is presented. A wide range of formamides can be used to produce the corresponding isocyanides in up to 99% yield. In a number of cases, the crude products showed good purity (generally >80% by NMR) allowing to be used directly in multi-component reactions.

Tetrahedron Letters 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

Decara, Juan M. published the artcileDiscovery of V-0219: A Small-Molecule Positive Allosteric Modulator of the Glucagon-Like Peptide-1 Receptor toward Oral Treatment for “Diabesity”, Quality Control of 39546-32-2, the publication is Journal of Medicinal Chemistry (2022), 65(7), 5449-5461, database is CAplus and MEDLINE.

Peptidic agonists of the glucagon-like peptide-1 receptor (GLP-1R) have gained a prominent role in the therapy of type-2 diabetes and are being considered for reducing food intake in obesity. Potential advantages of small mols. acting as pos. allosteric modulators (PAMs) of GLP-1R, including oral administration and reduced unwanted effects, could improve the utility of this class of drugs. Here, we describe the discovery of compound 9 (4-{[1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)piperidin-3-yl]methyl}morpholine, V-0219) that exhibits enhanced efficacy of GLP-1R stimulation, subnanomolar potency in the potentiation of insulin secretion, and no significant off-target activities. The identified GLP-1R PAM shows a remarkable in vivo activity, reducing food intake and improving glucose handling in normal and diabetic rodents. Enantioselective synthesis revealed oral efficacy for (S)-9 in animal models. Compound 9 behavior bolsters the interest of a small-mol. PAM of GLP-1R as a promising therapeutic approach for the increasingly prevalent obesity-associated diabetes.

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

Pettenuzzo, Andrea published the artcileDesign, physico-chemical characterization and in vitro biological activity of organogold(III) glycoconjugates, SDS of cas: 39546-32-2, the publication is Dalton Transactions (2021), 50(25), 8963-8979, database is CAplus and MEDLINE.

To develop new metal-based glycoconjugates as potential anticancer agents, four organometallic Au(III)-dithiocarbamato glycoconjugates [Au(III)(2-Bnpy)(SSC-Inp-GlcN)](PF₆) (2-Bnpy: 2-benzylpyridine; Inp: isonipecotic moiety; GlcN: amino-glucose scaffold; Au3-Au6) and the corresponding model nonglycosylated counterparts [Au(III)(2-Bnpy)(SSC-Inp-R)](PF₆) (R: OEt (Au1), NH₂ (Au2)) were generated and characterized by several anal. techniques (elemental anal., FTIR, ¹H-/¹³C-NMR, ESI-MS, UV-visible, x-ray crystallog.). Their stability under physiol.-relevant conditions (PBS solution) and n-octanol/PBS distribution coefficient (D_7.4) also were evaluated. Au(III) glycoconjugates showed an antiproliferative effect against ovarian carcinoma A2780 cells, with GI₅₀ values in the low micromolar range. Remarkably, their cell growth inhibitory effect increases upon the addition of a glucose transporter 1 (GLUT1) inhibitor, thus ruling out the involvement of GLUT1 in their transport inside the cell. Addnl. mechanistic studies were carried out in A2780 cells, supporting the hypothesis of a facilitated diffusion mechanism (possibly mediated by glucose transporters other than GLUT1), and revealing their capability to act as topoisomerase I and II inhibitors and to disrupt mitochondrial membrane integrity, giving ROS, thus resulting in the promotion of oxidative stress and, eventually, cell death.

Dalton Transactions 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, SDS of cas: 39546-32-2.

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

Pettenuzzo, Andrea published the artcileAn innovative and efficient route to the synthesis of metal-based glycoconjugates: proof-of-concept and potential applications, Safety of Piperidine-4-carboxamide, the publication is Dalton Transactions (2018), 47(31), 10721-10736, database is CAplus and MEDLINE.

With a view to developing more efficient strategies to the functionalization of metallodrugs with carbohydrates, the authors here report on an innovative and efficient synthetic route to generate Au(III) glycoconjugates in high yields and purity. The method is based on the initial synthesis of the Zn(II)-dithiocarbamato intermediate [Zn^II(SSC-Inp-GlcN)₂] (Inp = isonipecotic moiety; GlcN = amino-glucose) followed by the transfer of the glucoseisonipecoticdithiocarbamato ligand to the Au(III) center via transmetalation reaction between the Zn(II) intermediate and K[Au^IIIBr₄] in 1 : 2 stoichiometric ratio, yielding the corresponding glucose-functionalized Au(II)-dithiocarbamato derivative [Au^IIIBr₂(SSC-Inp-GlcN)]. No protection/deprotection of the amino-glucose scaffold and no chromatog. purification were needed. The synthetic protocol was optimized for glucose precursors bearing the amino function at either the C² or the C⁶ position, and works in the case of both α and β anomers. The application of the synthetic strategy was also successfully extended to other metal ions of biomedical interest, such as Au(I) and Pt(II), to obtain [Au^I(SSC-Inp-GlcN)(PPh₃)] and [Pt^II(SSC-Inp-GlcN)₂], resp. All compounds were fully characterized by elemental anal., mid- and far-IR, mono- and multidimensional NMR spectroscopy, and, where possible, x-ray crystallog. Results and potential applications are here discussed.

Dalton Transactions 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, Safety of Piperidine-4-carboxamide.

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