Month: November 2022

Yang, Renjing published the artcileSynthesis and Anti-Hepatoma Activities of U12 Derivatives Arresting G0/G1 Phase and Inducing Apoptosis by PI3K/AKT/mTOR Pathway, Recommanded Product: (E)-1-Cinnamylpiperazine, the publication is Pharmaceuticals (2022), 15(1), 107, database is CAplus and MEDLINE.

In this study, the structural modification and optimization of U12 were further investigated and twelve U12 derivatives I [R = aminocyclopropyl, piperazin-1-yl, 4-methylanilino, etc.], II were synthesized by substitution, esterification and amidation reactions. The evaluation of the cytotoxicity of synthetic derivatives against hepatoma cell lines (HepG2) indicated that II, I [R = 4-benzylpiperazin-1-yl, [4-[(E)-cinnamyl]piperazin-1-yl], piperazin-1-yl, aziridin-1-yl, 4-hydroxyanilino] showed more effective cytotoxic effects on the growth of HepG2 cells than U12, and the preliminary structure-activity relationship was discussed. Among them, compound I [R = 4-benzylpiperazin-1-yl] exhibited the most potent anti-hepatocellular carcinoma activity. Mechanism studies indicated that compound I [R = (4-benzylpiperazin-1-yl)] inhibited HepG2 cell proliferation by arresting the G0/G1 phase, and suppressed the activation of the PI3K/AKT/mTOR pathway. Further studies showed that compound I [R = 4-benzylpiperazin-1-yl] induced HepG2 cells apoptosis through activating the caspase signaling pathway. Furthermore, compound I [R = (4-benzylpiperazin-1-yl)] evidently inhibited the growth of HepG2-derived tumor xenografts in vivo without observable adverse effects. Thus, compound I [R = 4-benzylpiperazin-1-yl] might be considered as a promising candidate for the treatment of hepatocellular carcinoma.

Pharmaceuticals 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 C4H11NO, Recommanded Product: (E)-1-Cinnamylpiperazine.

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

Grycova, Aneta published the artcileImpurities contained in antifungal drug ketoconazole are potent activators of human aryl hydrocarbon receptor, Related Products of piperazines, the publication is Toxicology Letters (2015), 239(2), 67-72, database is CAplus and MEDLINE.

Antifungal drug ketoconazole is a mixture of (+)/(-) cis-enantiomers, which also contains several impurities. Ketoconazole was identified as an activator of aryl hydrocarbon receptor AhR by three independent research teams. In the current paper impurities contained in ketoconazole preparations are strong activators of human AhR and inducers of CYP1A1. Impurity IMP-C had similar potency (EC₅₀), but 10-15 times higher efficacy (magnitude of induction) towards AhR, comparing to (+)-ketoconazole, as revealed by gene reporter assay in AZ-AHR stably transfected cells. Impurities IMP-B and IMP-C, and in lesser extent IMP-E, induced a formation of AhR-DNA complex, as demonstrated by electromobility shift assay EMSA. Impurities IMP-C and IMP-E dose-dependently induced CYP1A1 mRNA after 24 h, and their effects were comparable to those by (+)-ketoconazole. The level of CYP1A1 protein in HepG2 cells was strongly increased by IMP-C after 48 h. In conclusion, the authors’ data further elucidated mol. effects of ketoconazole towards AhR signaling pathway, with possible implications in ketoconazole role in skin chemoprevention and/or damage, involving AhR.

Toxicology Letters 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, Related Products of piperazines.

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

Pedersen, Simon S. published the artcileA Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides, Recommanded Product: (E)-1-Cinnamylpiperazine, the publication is Chemistry – A European Journal (2021), 27(24), 7114-7123, database is CAplus and MEDLINE.

A series of pharmaceutically relevant small mols. and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon-13. Key to the success of this novel carbon isotope labeling technique is the observation that ¹³C-labeled Ni(II)-acyl complexes, formed from a ¹³CO insertion step with Ni(II)-alkyl intermediates, rapidly react in less than one minute with 2,2′-dipyridyl disulfide to quant. form the corresponding 2-pyridyl thioesters. Either the use of ¹³C-SilaCOgen or ¹³C-COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one-pot acylation of a series of structurally diverse amines provides the desired ¹³C-labeled carboxamides in good yields. A single electron transfer pathway is proposed between the Ni(II)-acyl complexes and the disulfide providing a reactive Ni(III)-acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chem. for carbon-11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of ¹³C-labeled liraglutide and insulin degludec, representing two antidiabetic drugs.

Chemistry – A European Journal 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, Recommanded Product: (E)-1-Cinnamylpiperazine.

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

Neumann, Karoline T. published the artcileSynthesis of Aliphatic Carboxamides Mediated by Nickel NN₂-Pincer Complexes and Adaptation to Carbon-Isotope Labeling, Recommanded Product: (E)-1-Cinnamylpiperazine, the publication is Chemistry – A European Journal (2018), 24(56), 14946-14949, database is CAplus and MEDLINE.

The development of a nickel-mediated aminocarbonylation utilizing NN₂-pincer Ni-complexes, alkylzinc reagents, stoichiometric carbon monoxide and amines is described for the first time, which can be adapted to late-stage carbon-isotope labeling. This work expands the scope of the highly established palladium-promoted version of the reaction, by allowing carbon-sp³ fragments to take part in the three-component reaction. Finally, the results obtained show a remarkable effect of the pincer ligand for the reductive elimination step with the amine, which is followed by 13C NMR spectroscopy studies.

Chemistry – A European Journal 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, Recommanded Product: (E)-1-Cinnamylpiperazine.

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

Xie, Lan-Gui published the artcileIridium-catalyzed reductive Ugi-type reactions of tertiary amides, COA of Formula: C13H18N2, the publication is Nature Communications (2018), 9(1), 1-8, database is CAplus and MEDLINE.

A series of Ugi-type reactions of tertiary amides enabled by an initial chemoselective iridium-catalyzed partial reduction, followed by reaction with isocyanide and (thio)acetic acid or trimethylsilyl azide, thus providing a multicomponent synthesis of α-amino (thio)amide or α-amino tetrazole derivatives The reductive Ugi-type reactions were amenable to a broad range of amides and isocyanides and were applicable to late-stage functionalization of various bioactive mols. and pharmaceutical compounds

Nature Communications 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 C18H28N2O7, COA of Formula: C13H18N2.

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

Xie, Lan-Gui published the artcileTertiary amine synthesis via reductive coupling of amides with Grignard reagents, Recommanded Product: (E)-1-Cinnamylpiperazine, the publication is Chemical Science (2017), 8(11), 7492-7497, database is CAplus and MEDLINE.

A new iridium catalyzed reductive coupling reaction of Grignard reagents R¹MgX (R¹ = Me, H₂C:CH, Me₃SiCH₂, n-C₅H₁₁, PhCH₂, etc.; X = Cl, Br) and tertiary amides R²C(O)NR³R⁴ (R² = Ph, 4-MeOC₆H₄, 2-furyl, etc.; R³R⁴N = 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, etc; R³ = Me, MeO, Ph, PhCH₂, R⁴ = Me; etc.) affording functionalised tertiary amine products R¹R²CHNR³R⁴ via an efficient and tech.-simple one-pot, two-stage exptl. protocol, is reported. The reaction, which can be carried out on gram-scale using as little as 1 mol% Vaska’s complex [IrCl(CO)(PPh₃)₂] and tetramethyldisiloxane as the terminal reductant for the initial reductive activation step, tolerates a broad range of tertiary amides from (hetero)aromatic to aliphatic (branched, unbranched and formyl) and a wide variety of alkyl (linear, branched), vinyl, alkynyl and (hetero)aryl Grignard reagents. The new methodol. has been applied directly to bioactive mol. synthesis and the high chemoselectivity of the reductive coupling of amide has been exploited in late stage functionalization of drug mols. This reductive functionalisation of tertiary amides provides a new and practical solution to tertiary amine synthesis.

Chemical Science 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 C12H9NO, Recommanded Product: (E)-1-Cinnamylpiperazine.

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

Fernandez, Ariadna published the artcilePiperazinyl Bicyclic Derivatives as Selective Ligands of the α2δ-1 Subunit of Voltage-Gated Calcium Channels, Application In Synthesis of 207284-20-6, the publication is ACS Medicinal Chemistry Letters (2021), 12(11), 1802-1809, database is CAplus and MEDLINE.

The synthesis and pharmacol. activities of a new series of piperazinyl quinazolin-4-(3H)-one derivatives I [R¹ = H, 5-Br, 6-(4-pyridinyl), 8-Br, etc.; R² = 2-methoxyethyl, benzyl, 2-furylmethyl, etc.; R³ = H, Me, Pr, n-Bu, etc.; R⁴ = piperazin-1-yl, (3R,5S)-3,5-dimethylpiperazin-1-yl, (S)-3-methylpiperazin-1-yl, etc.] acting toward the α2δ-1 subunit of voltage-gated calcium channels (Cavα2δ-1) were reported. Different positions of a micromolar HTS hit were explored, and best activities were obtained for compounds I containing a small alkyl group in position 3 of the quinazolin-4-(3H)-one scaffold and a 3-methyl-piperazin-1-yl- or 3,5-dimethyl-piperazin-1-yl-Bu group in position 2. The activity was shown to reside in the R enantiomer of the chain in position 2, and several eutomers reached single digit nanomolar affinities. Final modification of the central scaffold to reduce lipophilicity provided the pyrido[4,3-d]pyrimidin-4(3H)-one II, which showed high selectivity for Cavα2δ-1 vs. Cavα2δ-2, probably linked to its improved analgesic efficacy-safety ratio in mice over pregabalin.

ACS Medicinal Chemistry Letters published new progress about 207284-20-6. 207284-20-6 belongs to piperazines, auxiliary class Piperazine,Chiral, name is (S)-2-Ethylpiperazine, and the molecular formula is C6H14N2, Application In Synthesis of 207284-20-6.

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

Zhang, Weihe published the artcileUNC2025, a Potent and Orally Bioavailable MER/FLT3 Dual Inhibitor, Related Products of piperazines, the publication is Journal of Medicinal Chemistry (2014), 57(16), 7031-7041, database is CAplus and MEDLINE.

We previously reported a potent small mol. Mer tyrosine kinase inhibitor UNC1062. However, its poor PK properties prevented further assessment in vivo. We report here the sequential modification of UNC1062 to address DMPK properties and yield a new potent and highly orally bioavailable Mer inhibitor, 11, capable of inhibiting Mer phosphorylation in vivo, following oral dosing as demonstrated by pharmaco-dynamic (PD) studies examining phospho-Mer in leukemic blasts from mouse bone marrow. Kinome profiling vs. more than 300 kinases in vitro and cellular selectivity assessments demonstrate that 11 has similar subnanomolar activity against Flt3, an addnl. important target in acute myelogenous leukemia (AML), with pharmacol. useful selectivity vs. other kinases examined

Journal of Medicinal Chemistry published new progress about 914610-39-2. 914610-39-2 belongs to piperazines, auxiliary class Piperazine,Boronic acid and ester,Sulfamide,Benzene,Piperazine,Boronate Esters,Boronic acid and ester,, name is 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine, and the molecular formula is C19H14Cl2, Related Products of piperazines.

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

Gitto, Rosaria published the artcileN-Substituted isoquinoline derivatives as potential AChE inhibitors, SDS of cas: 87179-40-6, the publication is Journal of Heterocyclic Chemistry (2010), 47(1), 54-62, database is CAplus.

N-Substituted donepezil-related 1,2,3,4-tetrahydroisoquinolines were prepared as potential acetyl choline esterase inhibitors. Microwave-assisted procedures and solution-phase parallel synthesis were chosen to optimize the synthetic approach and improve the yields. All synthesized compounds were tested for AChE inhibitory activity by colorimetry, and some of them displayed low inhibitory effects at μM concentrations

Journal of Heterocyclic 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, SDS of cas: 87179-40-6.

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

Crespo, Roberto A. published the artcileStructure-Guided Drug Design of 6-Substituted Adenosine Analogues as Potent Inhibitors of Mycobacterium tuberculosis Adenosine Kinase, SDS of cas: 180698-19-5, the publication is Journal of Medicinal Chemistry (2019), 62(9), 4483-4499, database is CAplus and MEDLINE.

Mycobacterium tuberculosis adenosine kinase (MtbAdoK) is an essential enzyme of Mtb and forms part of the purine salvage pathway within mycobacteria. Evidence suggests that the purine salvage pathway might play a crucial role in Mtb survival and persistence during its latent phase of infection. In these studies, we adopted a structural approach to the discovery, structure-guided design, and synthesis of a series of adenosine analogs that displayed inhibition constants ranging from 5 to 120 nM against the enzyme. Two of these compounds exhibited low micromolar activity against Mtb with half maximal effective inhibitory concentrations of 1.7 and 4.0 μM. Our selectivity and preliminary pharmacokinetic studies showed that the compounds possess a higher degree of specificity against MtbAdoK when compared with the human counterpart and are well tolerated in rodents, resp. Finally, crystallog. studies showed the mol. basis of inhibition, potency, and selectivity and revealed the presence of a potentially therapeutically relevant cavity unique to the MtbAdoK homodimer.

Journal of Medicinal Chemistry published new progress about 180698-19-5. 180698-19-5 belongs to piperazines, auxiliary class Piperazine,Benzene, name is 1-Biphenyl-4-yl-piperazine, and the molecular formula is C16H18N2, SDS of cas: 180698-19-5.

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