Category: piperazines

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

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

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

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

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

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

Irie, Osamu published the artcileDiscovery of selective and nonpeptidic cathepsin S inhibitors, Formula: C12H16N2O2, the publication is Bioorganic & Medicinal Chemistry Letters (2008), 18(14), 3959-3962, database is CAplus and MEDLINE.

Nonpeptidic, selective, and potent cathepsin S inhibitors were derived from an inhouse pyrrolopyrimidine cathepsin K inhibitor by modification of the P2 and P3 moieties. The pyrrolopyrimidine-based inhibitors show nanomolar inhibition of cathepsin S with over 100-fold selectivity against other cysteine proteases, including cathepsin K and L. Some of the inhibitors showed cellular activities in mouse splenocytes as well as oral bioavailabilities in rats.

Bioorganic & Medicinal Chemistry 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, Formula: C12H16N2O2.

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

Brossard, Dominique published the artcileSynthesis of bile acid derivatives and in vitro cytotoxic activity with pro-apoptotic process on multiple myeloma (KMS-11), glioblastoma multiforme (GBM), and colonic carcinoma (HCT-116) human cell lines, HPLC of Formula: 87179-40-6, the publication is European Journal of Medicinal Chemistry (2010), 45(7), 2912-2918, database is CAplus and MEDLINE.

The use of nitrogenous heterocycles as building blocks in the synthesis of conjugate bile acid derivatives was described. New piperazinyl bile acid derivatives I [R^7a = OH, R^7b = H, R¹² = OH, R²⁴ = 4-methyl-1-piperazinylamino, 4-(trans-cinnamyl)-1-piperazinyl; R^7a = H, R^7b = OH, R¹² = H, R²⁴ = 4-methyl-1-piperazinylamino, 4-(trans-cinnamyl)-1-piperazinyl; R^7a = OH, R^7b = H, R¹² = H, R²⁴ = 4-methyl-1-piperazinylamino, 4-(trans-cinnamyl)-1-piperazinyl] were synthesized and tested in vitro against various human cancer cells (GBM, KMS-11, HCT-116). The best pro-apoptotic activity was obtained with N-(4N-cinnamylpiperazin-1-yl)-3α,7β-dihydroxy-5β-cholan-24-amide I [R^7a = H, R^7b = OH, R¹² = H, R²⁴ = 4-(trans-cinnamyl)-1-piperazinyl] and N-(4N-cinnamyllpiperazin-1-yl)-3α,7α-dihydroxy-5β-cholan-24-amide I [R^7a = OH, R^7b = H, R¹² = H, R²⁴ = 4-(trans-cinnamyl)-1-piperazinyl] on these human cancer cell lines (IC₅₀: 8.5-31.4 μM). This activity was associated with nuclear and DNA fragmentation, demonstrating that I [R^7a = H, R^7b = OH, R¹² = H, R²⁴ = 4-(trans-cinnamyl)-1-piperazinyl] induces cell death by an apoptotic process as does I [R^7a = OH, R^7b = H, R¹² = H, R²⁴ = 4-(trans-cinnamyl)-1-piperazinyl]. This study shows the possibility of heterocycle-steroids as new anticancer agents with improved bioactivity and easy to synthesize.

European Journal of 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, HPLC of Formula: 87179-40-6.

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

Oshima, Shinji published the artcileStudy on the increased probability of detecting adverse drug reactions based on Bayes’ theorem: evaluation of the usefulness of information on the onset timing of adverse drug reactions, Recommanded Product: N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, the publication is Biological & Pharmaceutical Bulletin (2017), 40(9), 1389-1398, database is CAplus and MEDLINE.

In order to avoid adverse drug reactions (ADRs), pharmacists are reconstructing ADR-related information based on various types of data gathered from patients, and then providing this information to patients. Among the data provided to patients is the time-to-onset of ADRs after starting the medication (i.e., ADR onset timing information). However, a quant. evaluation of the effect of onset timing information offered by pharmacists on the probability of ADRs occurring in patients receiving this information has not been reported to date. In this study, we extracted 40 ADR-drug combinations from the data in the Japanese Adverse Drug Event Report database. By applying Bayes’ theorem to these combinations, we quant. evaluated the usefulness of onset timing information as an ADR detection predictor. As a result, when information on days after taking medication was added, 54 ADR-drug combinations showed a likelihood ratio (LR) in excess of 2. In particular, when considering the ADR-drug combination of anaphylactic shock with levofloxacin or loxoprofen, the number of days elapsed between start of medication and the onset of the ADR was 0, which corresponded to increased likelihood ratios (LRs) of 138.7301 or 58.4516, resp. When information from 1-7d after starting medication was added to the combination of liver disorder and acetaminophen, the LR was 11.1775. The results of this study indicate the clin. usefulness of offering information on ADR onset timing.

Biological & Pharmaceutical Bulletin published new progress about 863127-77-9. 863127-77-9 belongs to piperazines, auxiliary class TGF-beta/Smad,Bcr-Abl,Natural product, name is N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, and the molecular formula is C22H28ClN7O3S, Recommanded Product: N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate.

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

Cummings, David F. published the artcileThree amino acids in the D₂ dopamine receptor regulate selective ligand function and affinity, Related Products of piperazines, the publication is Journal of Neurochemistry (2009), 110(1), 45-57, database is CAplus and MEDLINE.

The D₂ dopamine receptor is an important therapeutic target for the treatment of psychotic, agitated, and abnormal behavioral states. To better understand the specific interactions of subtype-selective ligands with dopamine receptor subtypes, seven ligands with high selectivity (>120-fold) for the D₄ subtype of dopamine receptor were tested on wild-type and mutant D₂ receptors. Five of the selective ligands were observed to have 21-fold to 293-fold increases in D₂ receptor affinity when three non-conserved amino acids in TM2 and TM3 were mutated to the corresponding D₄ amino acids. The two ligands with the greatest improvement in affinity for the D₂ mutant receptor [i.e., 3-([4-(4-iodophenyl) piperazin-1-yl]methyl)-1H-pyrrolo[2,3-b]pyridine (L-750,667) and 1-[4-iodobenzyl]-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]- aminopiperidine (RBI-257)] were investigated in functional assays. Consistent with their higher affinity for the mutant than for the wild-type receptor, concentrations of L-750,667 or RBI-257 that produced large reductions in the potency of quinpirole’s functional response in the mutant did not significantly reduce quinpirole’s functional response in the wild-type D₂ receptor. In contrast to RBI-257 which is an antagonist at all receptors, L-750,667 is a partial agonist at the wild-type D₂ but an antagonist at both the mutant D₂ and wild-type D₄ receptors. Our study demonstrates for the first time that the TM2/3 microdomain of the D₂ dopamine receptor not only regulates the selective affinity of ligands, but in selected cases can also regulate their function. Utilizing a new docking technique that incorporates receptor backbone flexibility, the three non-conserved amino acids that encompass the TM2/3 microdomain were found to account in large part for the differences in intermol. steric contacts between the ligand and receptors. Consistent with the exptl. data, this model illustrates the interactions between a variety of subtype-selective ligands and the wild-type D₂, mutant D₂, or wild-type D₄ receptors.

Journal of Neurochemistry published new progress about 337972-47-1. 337972-47-1 belongs to piperazines, auxiliary class Inhibitor, name is 2-((4-(4-Chlorophenyl)piperazin-1-yl)methyl)pyrazolo[1,5-a]pyridine, and the molecular formula is C18H19ClN4, Related Products of piperazines.

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