Category: 374930-88-8

Shallal, Hassan M.; Faridi, Jesika S.; Russu, Wade A. published the artcile< Anti-tumor pyrimidinylpiperazines bind to the prosurvival Bcl-2 protein family member Bcl-XL>, Product Details of C13H19BrN4O2, the main research area is pyrimidinylpiperazine preparation Bcl XL protein inhibitor anticancer; piperazine pyrimidinyl preparation Bcl XL protein inhibitor anticancer.

Overexpression of prosurvival or underexpression of pro-death Bcl-2 family proteins can lead to cancer cell resistance to chemotherapy and radiation treatment. Inhibition of the prosurvival Bcl-2 family proteins has become a strategy for cancer therapy and inhibitors are currently being evaluated in the clinic both as single agents and in combination with established drugs. Here, we describe the design, synthesis, and evaluation of pyrimidinylpiperazines I (R = Et, X = H, F, OH, NO2, Y = H, Br, Cl, 1H-pyrazol-4-yl; R = PhCH2, X = H, F, OH, NO2, NH2, Y = H, Br, Cl, 1H-pyrazol-4-yl) that were discovered to be inhibitors of the prosurvival Bcl-2 protein family member Bcl-XL. This study identified compound I (R = PhCH2, X = H, Y = 1H-pyrazol-4-yl), which demonstrated a GI50 value of 8.4 μM against A549 lung adenocarcinoma cells and a binding affinity Ki value for Bcl-XL of 127 nM.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Product Details of C13H19BrN4O2.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Bachovchin, Kelly A.; Sharma, Amrita; Bag, Seema; Klug, Dana M.; Schneider, Katherine M.; Singh, Baljinder; Jalani, Hitesh B.; Buskes, Melissa J.; Mehta, Naimee; Tanghe, Scott; Momper, Jeremiah D.; Sciotti, Richard J.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Pollastri, Michael P.; Ferrins, Lori published the artcile< Improvement of aqueous solubility of lapatinib-derived analogues: identification of a quinolinimine lead for human African trypanosomiasis drug development>, Recommanded Product: tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate, the main research area is trypanosomiasis parasiticide quinolinimine lapatinib pharmacokinetics Trypanosoma brucei.

Lapatinib, an approved epidermal growth factor receptor inhibitor, was explored as a starting point for the synthesis of new hits against Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). Previous work culminated in I, which was part of a series typically associated with poor aqueous solubility In this report, we present various medicinal chem. strategies that were used to increase the aqueous solubility and improve the physicochem. profile without sacrificing antitrypanosomal potency. To rank trypanocidal hits, a new assay (summarized in a cytocidal effective concentration (CEC50)) was established, as part of the lead selection process. Increasing the sp3 carbon content of I resulted in II (0.19 μM EC50 against T. brucei and 990 μM aqueous solubility). Further chem. exploration of II yielded III, a trypanocidal quinolinimine (EC50: 0.013 μM; aqueous solubility: 880 μM; and CEC50: 0.18 μM). Compound III reduced parasitemia 109 fold in trypanosome-infected mice; it is an advanced lead for HAT drug development.

Journal of Medicinal Chemistry published new progress about Homo sapiens. 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Recommanded Product: tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Ortiz, Eliezer; Shezaf, Jonathan Z.; Chang, Yu-Hsiang; Goncalves, Theo P.; Huang, Kuo-Wei; Krische, Michael J. published the artcile< Understanding Halide Counterion Effects in Enantioselective Ruthenium-Catalyzed Carbonyl (α-Aryl)allylation: Alkynes as Latent Allenes and Trifluoroethanol-Enhanced Turnover in The Conversion of Ethanol to Higher Alcohols via Hydrogen Auto-transfer>, Product Details of C13H19BrN4O2, the main research area is homoallylic alc preparation enantioselective; aryl propyne ethanol coupling ruthenium halide counterion effect.

Crystallog. characterization of RuX(CO)(η3-C3H5)(JOSIPHOS), where X = Cl, Br, or I, reveals a halide-dependent diastereomeric preference that defines metal-centered stereogenicity and, therefrom, the enantioselectivity of C-C coupling in ruthenium-catalyzed anti-diastereo- and enantioselective C-C couplings of primary alcs. with 1-aryl-1-propynes to form products of carbonyl anti-(α-aryl)allylation. Computational studies reveal that a non-classical hydrogen bond between iodide and the aldehyde formyl CH bond stabilizes the favored transition state for carbonyl addition An improved catalytic system enabling previously unattainable transformations was developed that employs an iodide-containing precatalyst, RuI(CO)3(η3-C3H5), in combination with trifluoroethanol, as illustrated by the first enantioselective ruthenium-catalyzed C-C couplings of ethanol to form higher alcs.

Journal of the American Chemical Society published new progress about Alkynes, aryl Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Product Details of C13H19BrN4O2.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Yi, Jun; Badir, Shorouk O.; Kammer, Lisa Marie; Ribagorda, Maria; Molander, Gary A. published the artcile< Deaminative Reductive Arylation Enabled by Nickel/Photoredox Dual Catalysis>, Safety of tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate, the main research area is deaminative reductive arylation nickel photoredox catalyst.

Described is a cross-electrophilic, deaminative coupling strategy harnessing Katritzky salts as a new species of electrophile in Ni/photoredox dual catalytic reductive cross-coupling reactions. Distinguishing features of this arylation protocol include its mild reaction conditions, high chemoselectivity, and adaptability to a variety of complex substrates [i.e., pyridinium salts derived from amines and partners derived from (hetero)aryl bromides].

Organic Letters published new progress about Bromides Role: RCT (Reactant), RACT (Reactant or Reagent) ((hetero)aryl). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Safety of tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Spinello, Brian J.; Wu, Jessica; Cho, Yoon; Krische, Michael J. published the artcile< Conversion of Primary Alcohols and Butadiene to Branched Ketones via Merged Transfer Hydrogenative Carbonyl Addition-Redox Isomerization Catalyzed by Rhodium>, Formula: C13H19BrN4O2, the main research area is isobutyl ketone preparation; alc butadiene tandem carbonyl addition redox isomerization rhodium catalyst; aldehyde butadiene tandem reductive coupling redox isomerization rhodium catalyst.

The first examples of rhodium-catalyzed carbonyl addition via hydrogen autotransfer were described, as illustrated in tandem butadiene-mediated carbonyl addition-redox isomerizations that directly converted primary alcs. to iso-Bu ketones RC(O)CH(Me)Et [R = 3-MeOC6H4, 3,4,5-tri-MeOC6H2, benzothiophen-5-yl, etc.]. Related reductive coupling-redox isomerizations of aldehyde reactants mediated by sodium formate also were reported. A double-labeling crossover experiment revealed that the rhodium alkoxide obtained upon carbonyl addition enacted redox isomerization without dissociation of rhodium at any intervening stage.

Journal of the American Chemical Society published new progress about Addition reaction. 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Formula: C13H19BrN4O2.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Rabal, Obdulia; Sanchez-Arias, Juan A.; Cuadrado-Tejedor, Mar; de Miguel, Irene; Perez-Gonzalez, Marta; Garcia-Barroso, Carolina; Ugarte, Ana; Estella-Hermoso de Mendoza, Ander; Saez, Elena; Espelosin, Maria; Ursua, Susana; Haizhong, Tan; Wei, Wu; Musheng, Xu; Garcia-Osta, Ana; Oyarzabal, Julen published the artcile< Discovery of in Vivo Chemical Probes for Treating Alzheimer's Disease: Dual Phosphodiesterase 5 (PDE5) and Class I Histone Deacetylase Selective Inhibitors>, Formula: C13H19BrN4O2, the main research area is sildenafil vardenafil orthoaminoanilide synthesis antiAlzheimer SAR PDE5 histone deacetylase; Alzheimer’s disease; PDE5 inhibition; chemical probes; class I HDAC selective inhibition; dual inhibitors; in vivo test.

In order to determine the contributions of histone deacetylase (HDAC) isoforms to the beneficial effects of dual phosphodiesterase 5 (PDE5) and pan-HDAC inhibitors on in vivo models of Alzheimer’s disease (AD), we have designed, synthesized, and tested novel chem. probes with the desired target compound profile of PDE5 and class I HDAC selective inhibitors. Compared to previous hydroxamate-based series, these mols. exhibit longer residence times on HDACs. In this scenario, shorter or longer preincubation times may have a significant impact on the IC50 values of these compounds and therefore on their corresponding selectivity profiles on the different HDAC isoforms. On the other hand, different chem. series have been explored and, as expected, some pairwise comparisons show a clear impact of the scaffold on biol. responses. The lead identification process led to compound I, which shows an adequate ADME-Tox profile and in vivo target engagement (histone acetylation and cAMP/cGMP response element-binding (CREB) phosphorylation) in the central nervous system (CNS), suggesting that this compound represents an optimized chem. probe; thus, I has been assayed in a mouse model of AD (Tg2576).

ACS Chemical Neuroscience published new progress about Alzheimer disease. 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Formula: C13H19BrN4O2.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Phelan, James P.; Wiles, Rebecca J.; Lang, Simon B.; Kelly, Christopher B.; Molander, Gary A. published the artcile< Correction: Rapid access to diverse, trifluoromethyl-substituted alkenes using complementary strategies [Erratum to document cited in CA169:178001]>, Formula: C13H19BrN4O2, the main research area is trifluoromethyl alkene preparation erratum; silyl alc trifluoromethyl cross coupling palladium erratum; Peterson elimination erratum; organotrifluoroborate cross coupling palladium erratum.

in the original article the Electronic Supplementary Information footnote included addnl. incorrect CCDC numbers for the crystal data reported; the correction is provided here.

Chemical Science published new progress about Addition reaction. 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Formula: C13H19BrN4O2.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Donald, Craig S.; Moss, Thomas A.; Noonan, Gary M.; Roberts, Bryan; Durham, Emma C. published the artcile< Deuterodehalogenation, a mild method for synthesising deuterated heterocycles>, Application In Synthesis of 374930-88-8, the main research area is heterocyclic halide ethyldeuterosilane deuteroisopropanol deuterodehalogenation palladium catalyst; deuterated heterocycle preparation.

This article reported a mild and efficient method for introducing deuterium into a range of heterocycles by reacting readily available halide analogs in a deuterodehalogenation reaction using D8-isopropanol or Et3SiD under palladium-catalyzed condition.

Tetrahedron Letters published new progress about Dehalogenation. 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Application In Synthesis of 374930-88-8.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Scott, James S.; Birch, Alan M.; Brocklehurst, Katy J.; Broo, Anders; Brown, Hayley S.; Butlin, Roger J.; Clarke, David S.; Davidsson, Ojvind; Ertan, Anne; Goldberg, Kristin; Groombridge, Sam D.; Hudson, Julian A.; Laber, David; Leach, Andrew G.; MacFaul, Philip A.; McKerrecher, Darren; Pickup, Adrian; Schofield, Paul; Svensson, Per H.; Sorme, Pernilla; Teague, Joanne published the artcile< Use of Small-Molecule Crystal Structures To Address Solubility in a Novel Series of G Protein Coupled Receptor 119 Agonists: Optimization of a Lead and in Vivo Evaluation>, Recommanded Product: tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate, the main research area is antidiabetic GPCR119 agonist preparation structure activity crystal structure.

G protein coupled receptor 119 (GPR119) is viewed as an attractive target for the treatment of type 2 diabetes and other elements of the metabolic syndrome. During a program toward discovering agonists of GPR119, we herein describe optimization of an initial lead compound, 2, into a development candidate, 42. A key challenge in this program of work was the insolubility of the lead compound Small-mol. crystallog. was utilized to understand the intermol. interactions in the solid state and resulted in a switch from an aryl sulfone to a 3-cyanopyridyl motif. The compound was shown to be effective in wild-type but not knockout animals, confirming that the biol. effects were due to GPR119 agonism.

Journal of Medicinal Chemistry published new progress about 5-HT2B receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Recommanded Product: tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Jouffroy, Matthieu; Primer, David N.; Molander, Gary A. published the artcile< Base-Free Photoredox/Nickel Dual-Catalytic Cross-Coupling of Ammonium Alkylsilicates>, Computed Properties of 374930-88-8, the main research area is photoredox nickel catalyzed coupling ammonium alkylsilicate hetero aryl bromide.

Single-electron transmetalation is recognized as an enabling technol. for the mild transfer of alkyl groups to transition metal catalysts in cross-coupling reactions. Hypercoordinate silicates represent a new and improved class of radical precursors because of their low oxidation potentials and the innocuous byproducts generated upon oxidation Herein, authors report the cross-coupling of secondary and primary ammonium alkylsilicates with (hetero)aryl bromides in good to excellent yields. The base-free conditions have exceptional protic group tolerance on both partners, permitting the cross-coupling of unprotected primary and secondary amines.

Journal of the American Chemical Society published new progress about Aryl bromides Role: RCT (Reactant), RACT (Reactant or Reagent) (hetero). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Computed Properties of 374930-88-8.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics