Month: November 2022

Kulkarni, B. published the artcileDesign, synthesis and molecular docking studies of some 1-(5-(2-fluoro-5-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-3-yl)piperazine derivatives as potential anti-inflammatory agents, Category: piperazines, the publication is Molecular Diversity, database is CAplus and MEDLINE.

The facile synthesis of a series of piperazinyl-substituted 1,2,4-oxadiazoles I (R = 4-ClC₆H₄CH₂, PhSO₂, 2-pyrazinylcarbonyl, etc.) in good to excellent yields is reported. The anti-inflammatory potential of the newly synthesized compounds was evaluated by anti-denaturation assay using diclofenac sodium as the reference standard Some of the compounds exhibited profound activity profile when compared to the standard drug. The mol. docking and SAR studies were carried out at the later stage to gain more insights about the promising activity profile of the synthesized mols.

Molecular Diversity published new progress about 113534-02-4. 113534-02-4 belongs to piperazines, auxiliary class Piperazine,Nitrile,Amide, name is tert-Butyl 4-cyanopiperazine-1-carboxylate, and the molecular formula is C10H17N3O2, Category: piperazines.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Beyzavi, Hudson published the artcile¹⁸F-Deoxyfluorination of Phenols via Ru π-Complexes, COA of Formula: C12H16N2O2, the publication is ACS Central Science (2017), 3(9), 944-948, database is CAplus and MEDLINE.

The deficiency of robust and practical methods for ¹⁸F-radiofluorination is a bottleneck for positron emission tomog. (PET) tracer development. Here, we report the first transition-metal-assisted ¹⁸F-deoxyfluorination of phenols. The transformation benefits from readily available phenols as starting materials, tolerance of moisture and ambient atm., large substrate scope, and translatability to generate doses appropriate for PET imaging.

ACS Central Science published new progress about 67914-60-7. 67914-60-7 belongs to piperazines, auxiliary class Piperazine,Benzene,Phenol,Amide, name is 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, and the molecular formula is C12H16N2O2, COA of Formula: C12H16N2O2.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Prabhakaran, Jaya published the artcileSynthesis and in vivo evaluation of [¹¹C]MPTQ: A potential PET tracer for alpha2A-adrenergic receptors, Name: (E)-1-Cinnamylpiperazine, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(12), 3654-3657, database is CAplus and MEDLINE.

Radiosynthesis and in vivo evaluation of [N-methyl-¹¹C] 5-methyl-3-[4-(3-phenylallyl)-piperazin-1-ylmethyl]-3,3a,4,5-tetrahydroisoxazolo[4,3-c]quinoline, I (R = ¹¹CH₃)(II), a potential PET tracer for alpha2-adrenergic receptors is described. Syntheses of nonradioactive standard and corresponding desmethyl precursor I (R = Me, H) were achieved from 2-aminobenzaldehyde in 40% and 65% yields, resp. Methylation using [¹¹C]CH₃I in the presence of aqueous potassium hydroxide in DMSO afforded II in 25% yield (EOS, end of synthesis) with >99% chem. and radiochem. purities with a specific activity range from 3-4 Ci/μmol (n = 6). The total synthesis time was 30 min from EOB (end of bombardment). PET (Positron-emission tomog.) studies in anesthetized baboon show that II penetrates the BBB (blood brain barrier) and accumulates in alpha2A-AR enriched brain areas.

Bioorganic & Medicinal Chemistry Letters published new progress about 87179-40-6. 87179-40-6 belongs to piperazines, auxiliary class Benzenes, name is (E)-1-Cinnamylpiperazine, and the molecular formula is C13H18N2, Name: (E)-1-Cinnamylpiperazine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Wang, Chenxuan published the artcileInhibition of Δ-6 desaturase reduces fatty acid re-esterification in 3T3-L1 adipocytes independent of changes in n3-PUFA cellular content, Category: piperazines, the publication is Biochimica et Biophysica Acta, Molecular and Cell Biology of Lipids (2022), 1867(7), 159160, database is CAplus and MEDLINE.

Δ-6 Desaturase (D6D) is a key enzyme in the synthesis of long-chain polyunsaturated fatty acids (LC-PUFA). Evidence suggests that reduced D6D activity not only disrupts LC-PUFA production, but also impacts whole body lipid handling and body weight; however, the mechanisms remain largely unexplored. Therefore, we investigated the effect of D6D inhibition on the regulation of lipid accumulation in 3T3-L1 adipocytes with and without changes in n-3 PUFA content. 3T3-L1 cells were treated with a D6D inhibitor (SC-26196) in the presence or absence of α-linolenic acid (ALA) throughout differentiation. We found that D6D inhibition blocked the conversion of ALA to eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPAn-3) when ALA was supplemented, while no changes in n-3 PUFA content were observed in cells treated with the D6D inhibitor alone. D6D inhibited cells had reduced triacylglycerol (TAG) accumulation despite an EPA/DPA deficiency. In addition, analyses of cellular protein markers, as well as non-esterified fatty acids and glycerol release in medium, suggested an increase in lipolysis and a decrease in fatty acid re-esterification in D6D-inhibited cells, independent of n-3 PUFA changes. To provide further evidence, we treated cells with the D6D inhibitor in the presence or absence of EPA and compared them with ALA-treated cells. Although EPA further reduced TAG content, the reduced markers of fatty acid re-esterification were not affected by ALA or EPA. Collectively, this study provides new insight showing that D6D inhibition reduces TAG accumulation and fatty acid re-esterification in adipocytes independent of changes in n-3 PUFA cellular content.

Biochimica et Biophysica Acta, Molecular and Cell Biology of Lipids published new progress about 218136-59-5. 218136-59-5 belongs to piperazines, auxiliary class Metabolic Enzyme,D6D, name is 2,2-Diphenyl-5-(4-((pyridin-3-ylmethylene)amino)piperazin-1-yl)pentanenitrile, and the molecular formula is C13H16O2, Category: piperazines.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Schiaffella, Fausto published the artcileNovel ketoconazole analogues based on the replacement of 2,4-dichlorophenyl group with 1,4-benzothiazine moiety: Design, synthesis, and microbiological evaluation, Category: piperazines, the publication is Bioorganic & Medicinal Chemistry (2006), 14(15), 5196-5203, database is CAplus and MEDLINE.

As a part of a program to develop novel antifungal agents, new compounds which incorporate the 1,4-benzothiazine moiety into the structure of ketoconazole (KTZ) were prepared These compounds were computationally investigated to assess whether the 1,4-benzothiazine moiety was a suitable bioisosteric replacement for the 2,4-dichlorophenyl group of KTZ in order to obtain a more potent inhibition of CYP51 enzyme of Candida albicans. Results of preliminary microbiol. studies show that the racemic cis-7 analog has a good in vivo activity, comparable to that of KTZ, but the best activity was observed in the racemic trans-7 analog.

Bioorganic & Medicinal Chemistry published new progress about 67914-60-7. 67914-60-7 belongs to piperazines, auxiliary class Piperazine,Benzene,Phenol,Amide, name is 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, and the molecular formula is C12H16N2O2, Category: piperazines.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Heinz, Christoph published the artcileNi-Catalyzed Carbon-Carbon Bond-Forming Reductive Amination, Formula: C13H18N2, the publication is Journal of the American Chemical Society (2018), 140(6), 2292-2300, database is CAplus and MEDLINE.

This report describes a three-component, Ni-catalyzed reductive coupling that enables the convergent synthesis of tertiary benzhydryl amines (e.g. I), which are challenging to access by traditional reductive amination methodologies. The reaction makes use of iminium ions generated in situ from the condensation of secondary N-trimethylsilyl amines with benzaldehydes, and these species undergo reaction with several distinct classes of organic electrophiles. The synthetic value of this process is demonstrated by a single-step synthesis of antimigraine drug flunarizine (Sibelium) and high yielding derivatization of paroxetine (Paxil) and metoprolol (Lopressor). Mechanistic investigations support a sequential oxidative addition mechanism rather than a pathway proceeding via α-amino radical formation. Accordingly, application of catalytic conditions to an intramol. reductive coupling is demonstrated for the synthesis of endo- and exocyclic benzhydryl amines.

Journal of the American Chemical Society published new progress about 87179-40-6. 87179-40-6 belongs to piperazines, auxiliary class Benzenes, name is (E)-1-Cinnamylpiperazine, and the molecular formula is C13H18N2, Formula: C13H18N2.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Hayatshahi, Hamed S. published the artcileFactors Governing Selectivity of Dopamine Receptor Binding Compounds for D2R and D3R Subtypes, Formula: C11H13N3, the publication is Journal of Chemical Information and Modeling (2021), 61(6), 2829-2843, database is CAplus and MEDLINE.

Targeting the D3 dopamine receptor (D3R) is a promising pharmacotherapeutic strategy for the treatment of many disorders. The structure of the D3R is similar to the D2 dopamine receptor (D2R), especially in the transmembrane spanning regions that form the orthosteric binding site, making it difficult to identify D3R selective pharmacotherapeutic agents. Here, the authors examine the mol. basis for the high affinity D3R binding and D3R vs. D2R binding selectivity of substituted phenylpiperazine thiopheneamides. Removing the thiophenearylamide portion of the ligand consistently decreases the affinity of these ligands at D3R, while not affecting their affinity at the D2R. The authors’ long (>10μs) mol. dynamics simulations demonstrated that both dopamine receptor subtypes adopt two major conformations that the authors refer to as closed or open conformations, with D3R sampling the open conformation more frequently than D2R. The binding of ligands with conjoined orthosteric-allosteric binding moieties causes the closed conformation to populate more often in the trajectories. Also, significant differences were observed in the extracellular loops (ECL) of these two receptor subtypes leading to the identification of several residues that contribute differently to the ligand binding for the two receptors that could potentially contribute to ligand binding selectivity. The authors’ observations also suggest that the displacement of ordered water in the binding pocket of D3R contributes to the affinity of the compounds containing an allosteric binding motif. These studies provide a better understanding of how a bitopic mode of engagement can determine ligands that bind selectively to D2 and D3 dopamine receptor subtypes.

Journal of Chemical Information and Modeling published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Formula: C11H13N3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Chen, Yonghao published the artcileSynthesis of ketoconazole by phase-transfer catalysis, Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, the publication is Zhongguo Yiyao Gongye Zazhi (2008), 39(8), 564-566, database is CAplus.

Antifungal drug ketoconazole was synthesized by utilization of phase-transfer catalysis from [2-bromomethyl-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl]methanol via acylation, N-alkylation with imidazole and hydrolysis, formation the active ester with methanesulfonyl chloride, and then condensation with the side chain 1-acetyl-4-(4-hydroxyphenyl)piperazine. The overall yield was about 30%.

Zhongguo Yiyao Gongye Zazhi published new progress about 67914-60-7. 67914-60-7 belongs to piperazines, auxiliary class Piperazine,Benzene,Phenol,Amide, name is 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, and the molecular formula is C12H16N2O2, Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Guo, Jia-Lin published the artcileSynthesis and biological evaluation of 3-(piperidin-4-yl)isoxazolo[4,5-d]pyrimidine derivatives as novel PI3Kδ inhibitors, Recommanded Product: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, the publication is Chinese Chemical Letters (2015), 26(10), 1283-1288, database is CAplus.

An efficient synthesis of novel 3-(piperidin-4-yl)isoxazolo[4,5-d]pyrimidine scaffold has been designed and developed. A series of 5-phenylurea derivatives I [R¹ = H, CH₂CH₂NMe₂, iso-Pr, etc.; R² = Bn, H, or Et] were synthesized using this method. Their cytotoxic activities against breast cancer cell line BT-474 were evaluated by CCK-8 assay. Most of them showed potent anti-proliferative activities, of which compound 20 (I, R¹ = CH₂CH₂F and R² = Bn) and 21 (I, R¹ = Me and R² = Bn) exhibited IC₅₀s of 1.565 and 1.311 μM, resp. Furthermore, compound 20 and 21 also showed potent inhibitory activities against PI3Kδ with IC₅₀s of 0.286 and 0.452 μM, resp. These results indicate that these 3-(piperidin-4-yl)isoxazolo[4,5-d]pyrimidine derivatives are novel antitumor agents through the inhibition of PI3Kδ.

Chinese Chemical Letters published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C10H16N4, Recommanded Product: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Cheng, Xian-Chao published the artcileDesign, synthesis, and biological activities of novel Ligustrazine derivatives, Related Products of piperazines, the publication is Bioorganic & Medicinal Chemistry (2007), 15(10), 3315-3320, database is CAplus and MEDLINE.

A series of novel Ligustrazine derivatives was designed, synthesized, and assayed for their protective effects on damaged ECV-304 cells and antiplatelet aggregation activities. The results showed that most Ligustrazine derivatives exhibited lower EC₅₀ values for protective effects on the ECV-304 cells damaged by hydrogen peroxide in comparison with Ligustrazine. And some Ligustrazine derivatives presented better antiplatelet aggregation activities than Ligustrazine. The derivatives containing the bisphenylmethyl pharmacophore (7a-c) exhibited highest potency. Compound 7a displayed most potential protective effects on the ECV-304 cells damaged by hydrogen peroxide, and compound 7c was found to be the most active antiplatelet aggregation agent. Structure-activity relationships were briefly discussed.

Bioorganic & Medicinal Chemistry published new progress about 87179-40-6. 87179-40-6 belongs to piperazines, auxiliary class Benzenes, name is (E)-1-Cinnamylpiperazine, and the molecular formula is C13H18N2, Related Products of piperazines.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics