Category: piperazines

Faruk Mansoor, U. published the artcileDesign and synthesis of potent Gram-negative specific LpxC inhibitors, Application of 1-Biphenyl-4-yl-piperazine, the publication is Bioorganic & Medicinal Chemistry Letters (2011), 21(4), 1155-1161, database is CAplus and MEDLINE.

Antibiotic resistant hospital acquired infections are on the rise, creating an urgent need for novel bactericidal drugs. Enzymes involved in lipopolysaccharide (LPS) biosynthesis are attractive antibacterial targets since LPS is the major structural component of the outer membrane of Gram-neg. bacteria. Lipid A is an essential hydrophobic anchor of LPS and the first committed step in lipid A biosynthesis is catalyzed by a unique zinc dependent metalloamidase, UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC). LpxC is an attractive Gram-neg. only target that has been chem. validated by potent bactericidal hydroxamate inhibitors that work by coordination of the enzyme’s catalytic zinc ion. An exploratory chem. effort focused on expanding the SAR around hydroxamic acid zinc-binding warheads’ lead to the identification of novel compounds with enzyme potency and antibacterial activity similar to CHIR-090.

Bioorganic & Medicinal Chemistry Letters 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, Application of 1-Biphenyl-4-yl-piperazine.

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

Dholkawala, Fahd published the artcileSynthesis and characterization of brain penetrant prodrug of neuroprotective D-264: Potential therapeutic application in the treatment of Parkinson’s disease, HPLC of Formula: 180698-19-5, the publication is European Journal of Pharmaceutics and Biopharmaceutics (2016), 62-70, database is CAplus and MEDLINE.

Parkinson’s disease (PD) is one of the major debilitating neurodegenerative disorders affecting millions of people worldwide. Progressive loss of dopamine neurons resulting in development of motor dysfunction and other related non-motor symptoms is the hallmark of PD. Previously, we have reported on the neuroprotective property of a potent D3 preferring agonist D-264. In our goal to increase the bioavailability of D-264 in the brain, we have synthesized a modified cysteine based prodrug of D-264 and evaluated its potential in crossing the blood-brain barrier. Herein, we report the synthesis of a novel modified cysteine conjugated prodrug of potent neuroprotective D3 preferring agonist D-264 and systematic evaluation of the hydrolysis pattern of the prodrug to yield D-264 at different time intervals in rat plasma and brain homogenates using HPLC anal. Furthermore, we have also performed in vivo experiments with the prodrug to evaluate its enhanced brain penetration ability.

European Journal of Pharmaceutics and Biopharmaceutics 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, HPLC of Formula: 180698-19-5.

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

Zhao, Hong-Yi published the artcileDiscovery of Potent PROTACs Targeting EGFR Mutants through the Optimization of Covalent EGFR Ligands, Name: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, the publication is Journal of Medicinal Chemistry (2022), 65(6), 4709-4726, database is CAplus and MEDLINE.

To overcome the intractable problem of drug resistance, proteolysis targeting chimeras (PROTACs) targeting EGFR mutants were developed by optimizing covalent EGFR ligands. Covalent or reversible covalent pyrimidine- or purine-containing PROTACs were designed, synthesized, and evaluated. As a consequence, covalent PROTAC I, with a novel purine-containing EGFR ligand, was discovered as a highly potent degrader against EGFR^L858R/T790M and EGFR^del19, reaching the lowest DC₅₀ values among all reported EGFR-targeting PROTACs. Furthermore, I exhibited excellent cellular activity against the H1975 and HCC827 cell lines with high selectivity. Mechanism investigation indicated that the lysosome was involved in the degradation process. Importantly, the covalent binding strategy was proven to be an effective approach for the design of PROTACs targeting EGFR^L858R/T790M, which laid the practical foundation for further development of potent EGFR-targeting PROTACs.

Journal of Medicinal Chemistry 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 C12H16BBrO2, Name: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine.

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

Bruncko, Milan published the artcileStructure-Guided Design of a Series of MCL-1 Inhibitors with High Affinity and Selectivity, Product Details of C12H16N2O2, the publication is Journal of Medicinal Chemistry (2015), 58(5), 2180-2194, database is CAplus and MEDLINE.

Myeloid cell leukemia 1 (MCL-1) is a BCL-2 family protein that has been implicated in the progression and survival of multiple tumor types. Herein the authors report a series of MCL-1 inhibitors that emanated from a high throughput screening (HTS) hit and progressed via iterative cycles of structure-guided design. Advanced compounds from this series exhibited subnanomolar affinity for MCL-1 and excellent selectivity over other BCL-2 family proteins as well as multiple kinases and GPCRs. In a MCL-1 dependent human tumor cell line, administration of compound I rapidly induced caspase activation with associated loss in cell viability. The small mols. described herein thus comprise effective tools for studying MCL-1 biol.

Journal of 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, Product Details of C12H16N2O2.

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

Lodha, Kamlesh K. published the artcileExploring new tetrahydrothienopyridine derivatives as platelet agglutination inhibitors: synthesis, biological evaluation and In silico study, Quality Control of 67914-60-7, the publication is ChemistrySelect (2022), 7(2), e202103428, database is CAplus.

The P2Y12 receptor is the major target for antithrombic drugs which plays a key role in platelet activation. New derivatives of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine (THP) were designed targeting P2Y12 receptor. An efficient route was developed for synthesis of THP derivatives and subsequently evaluated for their antiplatelet agglutination activity. Amongst the synthesized THP derivatives (4 a-4 g), the compounds 4 a and 4 g displayed significant activity (with 88.25 and 70.17 % inhibition) as compared to other analogs and comparable with that of the reference drugs, aspirin and prasugrel. Data extracted from computational chem. techniques such as mol. docking, provided the structural rationale for the observed platelet agglutination inhibition by the newly synthesized tetrahydrothienopyridine analogs. We proposed the involvement of residues such as Cys-194 in the formation of the covalent adduct with the active metabolite of tetrahydrothienopyridine derivatives This study also put forward the possibility of the existence of an alternate pathway for metabolizing the tetrahydrothienopyridine compounds The structural data presented in this study is expected to accelerate the research on developing a tetrahydrothienopyridine scaffold as an effective antithrombotic therapeutic modality.

ChemistrySelect 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, Quality Control of 67914-60-7.

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

Obukowicz, Mark G. published the artcileNovel, selective Δ6 or Δ5 fatty acid desaturase inhibitors as antiinflammatory agents in mice, Name: 2,2-Diphenyl-5-(4-((pyridin-3-ylmethylene)amino)piperazin-1-yl)pentanenitrile, the publication is Journal of Pharmacology and Experimental Therapeutics (1998), 287(1), 157-166, database is CAplus.

Decreased synthesis of arachidonic acid by inhibition of the Δ6 or Δ5 desaturase was evaluated as a means to mitigate inflammation. Using quant. in vitro and in vivo radioassays, novel compounds representing five classes of Δ5 desaturase inhibitors and one class of Δ6 desaturase inhibitor were identified. The Δ6 desaturase inhibitor, SC-26196, had pharmacokinetic and pharmacodynamic profiles in mice that allowed for the evaluation of the pharmacol. effects of chronic inhibition of desaturase activity. SC-26196 decreased edema to the same extent as indomethacin or essential fatty acid deficiency in the carrageenan paw edema model in the mouse. The anti-inflammatory properties of SC-26196 were consistent with its mechanism of action as a Δ6 desaturase inhibitor: (1) A correlation existed between inhibition of liver Δ6 desaturase activity and decreases in edema. The onset of the decrease in edema was time dependent. Selective reduction of arachidonic acid occurred dose dependently in liver, plasma and peritoneal cells. In the presence of SC-26196, controlled refeeding of arachidonic acid, but not oleic acid, reversed the changes resulting from desaturase inhibition. The Δ6 desaturase may be a target for development of antiinflammatory drugs whose mechanism of action is unique.

Journal of Pharmacology and Experimental Therapeutics 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 C27H29N5, Name: 2,2-Diphenyl-5-(4-((pyridin-3-ylmethylene)amino)piperazin-1-yl)pentanenitrile.

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

Harrison, Bryce A. published the artcileNovel Class of LIM-Kinase 2 Inhibitors for the Treatment of Ocular Hypertension and Associated Glaucoma, Formula: C20H21BrN8, the publication is Journal of Medicinal Chemistry (2009), 52(21), 6515-6518, database is CAplus and MEDLINE.

The discovery of a pyrrolopyrimidine class of LIM-kinase 2 (LIMK2) inhibitors is reported. These LIMK2 inhibitors show good potency in enzymic and cellular assays and good selectivity against ROCK. After topical dosing to the eye in a steroid induced mouse model of ocular hypertension, the compounds reduce intraocular pressure to baseline levels. The compounds also increase outflow facility in a pig eye perfusion assay. These results suggest LIMK2 may be an effective target for treating ocular hypertension and associated glaucoma.

Journal of Medicinal Chemistry published new progress about 1116571-01-7. 1116571-01-7 belongs to piperazines, auxiliary class Other Aromatic Heterocyclic,Piperazine,Chiral,Nitrile,Bromide,Carbamidine,Amine,Benzene, name is (S)-N-(3-Bromophenyl)-N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide, and the molecular formula is C20H21BrN8, Formula: C20H21BrN8.

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

Sanz Sharley, Daniel D. published the artcileAcetic acid as a catalyst for the N-acylation of amines using esters as the acyl source, Related Products of piperazines, the publication is Chemical Communications (Cambridge, United Kingdom) (2017), 53(12), 2020-2023, database is CAplus and MEDLINE.

Authors report a cheap and simple method for the acetylation of a variety of amines using catalytic acetic acid and either Et acetate or Bu acetate as the acyl source. Catalyst loadings as low as 10 mol% afforded acetamide products in excellent yields at temperatures ranging from 80-120°. The methodol. can also be successfully applied for the synthesis of a broad range of other amides, including the formation of formamides at 20°.

Chemical Communications (Cambridge, United Kingdom) 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

Devine, William published the artcileProtozoan parasite growth inhibitors discovered by cross-screening yield potent scaffolds for lead discovery, Formula: C17H27BN2O4S, the publication is Journal of Medicinal Chemistry (2015), 58(14), 5522-5537, database is CAplus and MEDLINE.

Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have an estimated combined burden of over 87 million disability-adjusted life years. New drugs are needed for each of these diseases. Building on the previous identification of NEU-617 as a potent and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), the authors have now tested this class of analogs against other protozoal species: T. cruzi (Chagas disease), Leishmania major (cutaneous leishmaniasis), and Plasmodium falciparum (malaria). Based on hits identified in this screening campaign, the authors describe the preparation of several replacements for the quinazoline scaffold and report these inhibitors’ biol. activities against these parasites. In doing this, the authors have identified several potent proliferation inhibitors for each pathogen, such as NEU-924, I, for T. cruzi and NEU-1017, II, for L. major and P. falciparum.

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 C17H27BN2O4S, Formula: C17H27BN2O4S.

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

Xie, Chao published the artcileNatural Product Glycine Betaine as an Efficient Catalyst for Transformation of CO₂ with Amines to Synthesize N-Substituted Compounds, Safety of (E)-1-Cinnamylpiperazine, the publication is ACS Sustainable Chemistry & Engineering (2017), 5(8), 7086-7092, database is CAplus.

Transformation of carbon dioxide (CO₂) into value-added chems. is of great importance, and use of natural products as a catalyst is very interesting. Herein, we used the naturally occurring glycine betaine as an efficient and renewable catalyst for the formation of a C-N bond between CO₂ and amines using PhSiH₃ as the reductant. The effects of different factors on the reaction were studied. It was demonstrated that the catalyst was very active for the reactions, and a broad range of amine substrates could be converted with satisfactory yields. Moreover, the selectivity to different N-substituted compounds could be controlled by the molar ratio of reactants (i.e., CO₂, amines, and PhSiH₃) and the reaction temperature In the catalytic cycle, the carbon oxidation state of CO₂ could be reduced to +2, 0, and -2, resp., and thus, the corresponding formamides, aminals, and methylamines were produced via successive two-electron reduction steps.

ACS Sustainable Chemistry & Engineering 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 C2H5BF3K, Safety of (E)-1-Cinnamylpiperazine.

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