Month: November 2022

Rotstein, David M. published the artcileStereoisomers of ketoconazole: preparation and biological activity, SDS of cas: 67914-60-7, the publication is Journal of Medicinal Chemistry (1992), 35(15), 2818-25, database is CAplus and MEDLINE.

The four stereoisomers of the antifungal agent ketoconazole, (2S,4R)-, (2R,4R)-, (2R,4S)-, and (2S,4S)-(imidazolylmethyl)phenyl{[(acetylpiperazinyl)phenoxy]methyl}dioxolanes I, were prepared and evaluated for their selectivity in inhibiting a number of cytochrome P 450 enzymes. Thus, (bromomethyl)phenyldioxolanes II condensed with 4-(N-acetylpiperazino)phenol and imidazole to give I. II were prepared by bromination of 2′,4′-dichloroacetophenone followed by reaction with (S)- and (R)-solketal tosylate. Large differences in selectivity among the isomers were observed for inhibition of the cytochromes P 450 involved in steroid biosynthesis, whereas little difference was observed for inhibition of those associated with hepatic drug metabolism The cis-(2S,4R) and trans-(2R,4R) isomers are equipotent in inhibiting corticoid 11β-hydroxylase and much more effective than their antipodes. Little selectivity was observed for inhibition of cholesterol side chain cleavage or xenobiotic hydroxylases. These data indicate that the affinity of azoles for cytochrome P 450 enzymes involved in steroid synthesis is high dependent on the stereochem. of the entire mol., whereas binding to drug metabolizing enzymes is a less selective process.

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, SDS of cas: 67914-60-7.

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

Huang, Y. published the artcileSynthesis of potent and selective dopamine D₄ antagonists as candidate radioligands, Category: piperazines, the publication is Bioorganic & Medicinal Chemistry Letters (2001), 11(11), 1375-1377, database is CAplus and MEDLINE.

A series of dopamine D₄ antagonists, pyridinylpyrrolyl arylpiperazines I (R = F, MeO, R¹ = H; R = H, R¹ = F, MeO, MeS, CF₃, CH:CH₂, Et, Pr, Ph), was synthesized and evaluated as potential candidates for development as positron emission tomog. (PET) radioligands. Thus, azagramine II was reacted with the corresponding arylpiperazine in xylene under reflux to give I in 45 to 82% yield. All new compounds display high affinity and selectivity for the D₄ receptors and compounds I (R = H, R¹ = MeO; R = MeO, R1 = H; R = H, R¹ = MeS) were identified as candidates for radioligand development. The activity against serotonin receptors was also examined

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, Category: piperazines.

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

Hatnapure, Girish D. published the artcileSynthesis and biological evaluation of novel piperazine derivatives of flavone as potent anti-inflammatory and antimicrobial agent, Formula: C13H18N2, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(20), 6385-6390, database is CAplus and MEDLINE.

A series of 6-methoxy-2-(piperazin-1-yl)-4H-chromen-4-one and 5,7-dimethoxy-2-(piperazin-1-ylmethyl)-4H-chromen-4-one derivatives of biol. interest were prepared and screened for their pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Among all the title compound screened, seven compounds, e.g., I, were found to have promising anti-inflammatory activity (up to 65-87% TNF-α and 70-93% IL-6 inhibitory activity) at concentration of 10 μM with reference to standard dexamethasone (71% TNF-a and 84% IL-6 inhibitory activities at 1 μM) while five compounds were found to be potent antimicrobial agent showing even 2 to 2.5-fold more potency than that of standard ciprofloxacin and miconazole at the same MIC value of 10 μg/mL.

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, Formula: C13H18N2.

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

Patel, Gautam published the artcileKinase Scaffold Repurposing for Neglected Disease Drug Discovery: Discovery of an Efficacious, Lapatanib-Derived Lead Compound for Trypanosomiasis, Name: 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine, the publication is Journal of Medicinal Chemistry (2013), 56(10), 3820-3832, database is CAplus and MEDLINE.

Lapatinib analogs such as I (X = O, CH₂) were prepared as trypanocidal agents for use as lead compounds in the development of treatments for human African trypanosomiasis which do not require i.v. administration. Lapatinib was previously shown to kill T. brucei with low micromolar EC₅₀ values; analogs replacing the methylfurylquinazoline moiety with a heteroarylsulfonylphenylquinazolinyl moiety were prepared and tested against both T. brucei and human hepatocarcinoma cells. 4-Anilinoquinazolines, particularly I (X = O) (NEU617), were found to be highly potent and orally bioavailable inhibitors of trypanosome replication. I (X = O) blocks duplication of the kinetoplast and arrests cytokinesis in T. brucei, which may make it useful as a chem. tool for studying regulation of the trypanosome cell cycle.

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, Name: 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine.

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

Harmon, Shawn D. published the artcileEffect of the Δ⁶-desaturase inhibitor SC-26196 on PUFA metabolism in human cells, Related Products of piperazines, the publication is Lipids (2003), 38(4), 469-476, database is CAplus and MEDLINE.

The objective of this study was to determine the effect of 2,2-diphenyl-5-(4-{[(1E)-pyridin-3-yl-methylidene]-amino}piperazin-1-yl)pentanenitrile (SC-26196), a Δ⁶-desaturase inhibitor, on PUFA metabolism in human cells. SC-26196 inhibited the desaturation of 2 μM [1-¹⁴C]18:2n-6 by 87-95% in cultured human skin fibroblasts, coronary artery smooth muscle cells, and astrocytes. By contrast, SC-26196 did not affect the conversion of [1-¹⁴C]20:3n-6 to 20:4 in the fibroblasts, demonstrating that it is selective for Δ⁶-desaturase. The IC₅₀ values for inhibition of the desaturation of 2 μM [1-¹⁴C]18:3n-3 and [3-¹⁴C]24:5n-3 in the fibroblasts, 0.2-0.4 μM, were similar to those for the inhibition of [1-¹⁴C]18:2n-6 desaturation, and the rates of recovery of [1-¹⁴C]18:2n-6 and [3-¹⁴C]24:5n-3 desaturation after removal of SC-26196 from the culture medium also were similar. SC-26196 reduced the conversion of [3-¹⁴C]22:5n-3 and [3-¹⁴C]24:5n-3 to DHA by 75 and 84%, resp., but it had no effect on the retroconversion of [3-¹⁴C]24:6n-3 to DHA. These results demonstrate that SC-26196 effectively inhibits the desaturation of 18- and 24-carbon PUFA and, therefore, decreases the synthesis of arachidonic acid, EPA, and DHA in human cells. Furthermore, they provide addnl. evidence that the conversion of 22:5n-3 to DHA involves Δ⁶-desaturation

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 C27H29N5, Related Products of piperazines.

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

Lee, Hee-Yoon published the artcileStructure-activity relationship studies of the chromosome segregation inhibitor, Incentrom A, Application In Synthesis of 87179-40-6, the publication is Bioorganic & Medicinal Chemistry Letters (2008), 18(16), 4670-4674, database is CAplus and MEDLINE.

A series of Incentrom A analogs that inhibit the chromosome segregation process in yeast were synthesized and tested for their effects on chromosome stability and cell proliferation. Pharmacophore and structure-activity relationship of Incentrom A for the anti-yeast activity were established.

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, Application In Synthesis of 87179-40-6.

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

Harding, John R. published the artcileDevelopment of a microwave-enhanced isotopic labeling procedure based on the Eschweiler-Clarke methylation reaction, Application of (E)-1-Cinnamylpiperazine, the publication is Tetrahedron Letters (2002), 43(52), 9487-9488, database is CAplus.

A number of primary and secondary amines have been rapidly methylated under microwave-enhanced conditions using formic acid-formaldehyde mixtures, providing a route to ²H(D)-containing compounds and the potential for ³H(T), ¹¹C, ¹³C, and ¹⁴C labeling.

Tetrahedron 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, Application of (E)-1-Cinnamylpiperazine.

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

Ramesh, Deepthi published the artcileIndole chalcones: Design, synthesis, in vitro and in silico evaluation against Mycobacterium tuberculosis, Application of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, the publication is European Journal of Medicinal Chemistry (2020), 112358, database is CAplus and MEDLINE.

Indole chalcones were designed and synthesized as a promising set of compounds against H₃₇Rv strain of Mycobacterium tuberculosis. Within this library of compounds, (E)-1-(furan-3-yl)-3-(1H-indol-3-yl)prop-2-en-1-one (18), (E)-3-(1H-indol-3-yl)-1-(thiophen-2-yl)prop-2-en-1-one (20) and (E)-2-((1H-indol-2-yl)methylene)cyclopentan-1-one (24) displayed high anti-tubercular activity at 50 μg/mL with MIC values of 210, 197 and 236 μM resp. The in-silico studies revealed that compound 18 exhibit binding modes similar to FAS-II inhibitors like INH or Thiolactomycin against KasA protein. Cytotoxicity assay results suggest that the compounds 18, 20 and 24 are non-cytotoxic to human megakaryocytes and murine B cells.

European 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, Application of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone.

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

Cramer, Richard D. published the artcile“Lead Hopping”. Validation of Topomer Similarity as a Superior Predictor of Similar Biological Activities, Safety of 2-((4-(4-Chlorophenyl)piperazin-1-yl)methyl)pyrazolo[1,5-a]pyridine, the publication is Journal of Medicinal Chemistry (2004), 47(27), 6777-6791, database is CAplus and MEDLINE.

Two extensive studies quantifying the ability of topomer shape similarity to forecast a variety of biol. similarities are described. In a prospective trial of “lead hopping”, using topomer similarity for virtual screening and queries from the patent literature, biol. assays of 308 selected compounds (representing 0.03% of those available, per assay type) yielded 11 successful “lead hops” in the 13 assays attempted. The hit rate averaged over all assays was 39% (“activity” defined as inhibition ≥20% at 10 μM), significantly greater than an unexpectedly high neg. control hit rate of 15%. The average “Tanimoto 2D fingerprint similarity” between query and “lead hop” structures (0.36) was little more than the Tanimoto similarity between random drug-like structures. Topomer shape and Tanimoto 2D fingerprint similarities were also compared retrospectively, in their tendencies to concentrate together potential and actual drugs reported to belong to the same “activity class”, for twenty classes. Among the most similar 3% of structures (corresponding to “≥0.85 Tanimoto” for these structures), an average of 62% of the topomer similar selection possessed a near neighbor belonging to the same activity class, roughly a one-third superiority over the “Tanimoto ≥ 0.85” selection containing 48% actives in avoiding false positives. Conversely, the least similar 75% of structures contained 0.3% actives for topomer similarity vs. 1.0% actives for Tanimoto 2D fingerprint similarity, a 3-fold superiority for topomers in avoiding false negatives.

Journal of Medicinal Chemistry 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, Safety of 2-((4-(4-Chlorophenyl)piperazin-1-yl)methyl)pyrazolo[1,5-a]pyridine.

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

Bachovchin, Daniel A. published the artcileSuperfamily-wide portrait of serine hydrolase inhibition achieved by library-versus-library screening, Category: piperazines, the publication is Proceedings of the National Academy of Sciences of the United States of America (2010), 107(49), 20941-20946, S20941/1-S20941/172, database is CAplus and MEDLINE.

Serine hydrolases (SHs) are-one of the largest and most diverse enzyme classes in mammals. They play fundamental roles in virtually all physiol. processes and are targeted by drugs to treat diseases such as diabetes, obesity, and neurodegenerative disorders. Despite this, we lack biol. understanding for most of the 110+ predicted mammalian metabolic SHs, in large part because of a dearth of assays to assess their biochem. activities and a lack of selective inhibitors to probe their function in living systems. We show here that the vast majority (>80%) of mammalian metabolic SHs can be labeled in proteomes by a single, active site-directed fluorophosphonate probe. We exploit this universal activity-based assay in a library-vs.-library format to screen 70+ SHs against 140+ structurally diverse carbamates. Lead inhibitors were discovered for ∼40% of the screened enzymes, including many poorly characterized SHs: Global profiles identified carbamate inhibitors that discriminate among highly sequence-related SHs and, conversely, enzymes that share inhibitor sensitivity profiles despite lacking sequence homol. These findings indicate that sequence relatedness is not a strong predictor of shared pharmaol. within the SH superfamily. Finally, we show that lead carbamate inhibitors can be optimized into pharmacol. probes that inactivate individual SHs with high specificity in vivo.

Proceedings of the National Academy of Sciences of the United States of America 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