M.W=350-400 | Page 2 of 2 | Heterocyclic Building Blocks-piperazine

Mehta, Naimee’s team published research in ACS Infectious Diseases in 4 | CAS: 914610-39-2

ACS Infectious Diseases 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, Category: piperazines.

Mehta, Naimee published the artcileOptimization of Physicochemical Properties for 4-Anilinoquinoline Inhibitors of Plasmodium falciparum Proliferation, Category: piperazines, the publication is ACS Infectious Diseases (2018), 4(4), 577-591, database is CAplus and MEDLINE.

The authors recently reported the medicinal chem. reoptimization of a known human tyrosine kinase inhibitor, lapatinib, against a variety of parasites responsible for numerous tropical diseases, including human African trypanosomiasis (Trypanosoma brucei), Chagas disease (T. cruzi), Leishmaniasis (Leishmania spp.), and malaria (Plasmodium falciparum). Herein, the authors report the authors’ continuing efforts to optimize this series against P. falciparum. Through the design of a library of compounds focused on reducing the lipophilicity and mol. weight, followed by an SAR exploration, the authors have identified NEU-1953 (40). This compound is a potent inhibitor of P. falciparum with an improved ADME profile over the previously reported compound, NEU-961.

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

Zhang, Weihe’s team published research in Journal of Medicinal Chemistry in 57 | CAS: 914610-39-2

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.

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

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

Juen, Ludovic’s team published research in Journal of Medicinal Chemistry in 60 | CAS: 914610-39-2

Juen, Ludovic published the artcileNew Inhibitor Targeting Signal Transducer and Activator of Transcription 5 (STAT5) Signaling in Myeloid Leukemias, COA of Formula: C17H27BN2O4S, the publication is Journal of Medicinal Chemistry (2017), 60(14), 6119-6136, database is CAplus and MEDLINE.

Signal Transducer and Activator of Transcription 5 (STAT5) are crucial effectors of tyrosine kinase oncogenes in myeloid leukemias. Inhibition of STAT5 would contribute to reducing the survival of leukemic cells and also tackling their chemoresistance. In a first screening experiment, the authors identified hit 13 (I) as able to inhibit STAT5 phosphorylation and leukemic cell growth. The synthesis of 18 analogs of 13 allowed the authors to identify one compound, 17f (II), as having the most potent antileukemic effect. Compound 17f inhibited the growth of acute and chronic myeloid leukemia cells and phosphorylation and transcriptional activity of STAT5. Importantly, 17f had minimal effects on bone marrow stromal cells that play vital functions in the microenvironment of hematopoietic and leukemic cells. The authors also demonstrated that 17f inhibits STAT5 but not STAT3, AKT or Erk1/2 phosphorylation. These results suggest that 17f might be a new lead mol. targeting STAT5 signaling in myeloid leukemias.

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

Kaoukabi, Asma’s team published research in Journal of Heterocyclic Chemistry in 56 | CAS: 914610-39-2

Journal of Heterocyclic 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, Recommanded Product: 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine.

Kaoukabi, Asma published the artcileEfficient Synthesis of New 2H-Chromene Retinoid Hybrid Derivatives by Suzuki Cross-Coupling Reactions, Recommanded Product: 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine, the publication is Journal of Heterocyclic Chemistry (2019), 56(4), 1260-1274, database is CAplus.

In an attempt to improve anticancer activity, a series of retinoid-chromene hybrids were prepared The novel heterocyclic chromene-retinoid hybrids that include oxygen as a heteroatom in a six-membered cyclic ring (2H-chromene or 2H-1-benzopyran) were designed and synthesized by introducing different groups such as an aromatic or styrylphenyl group in the 6-position of 2H-chromene. These novel compounds were synthesized by using the efficient cascade one-pot process involving Wittig-Horner-Emmons reaction and Suzuki-Miyaura cross-coupling palladium-catalyzed reactions with 60% to 90% overall yields. These new compounds were tested against glioblastoma multiforme brain cancer, medulloblastoma, neuroblastoma cell lines and breast cancer MCF-7 cell lines. Two of them exhibited an appreciable antitumor activity in the low micromolar range, which opens new perspectives for therapeutic application on humans.

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

Hansen, Hanne D.’s team published research in European Journal of Medicinal Chemistry in 2014-05-22 | CAS: 1073354-42-3

European Journal of Medicinal Chemistry published new progress about 5-HT1A receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1073354-42-3 belongs to class piperazines, name is tert-Butyl 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine-1-carboxylate, and the molecular formula is C20H32BN3O4, Recommanded Product: tert-Butyl 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine-1-carboxylate.

Hansen, Hanne D. published the artcileSynthesis, radiolabeling and in vivo evaluation of [11C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT7 receptor, Recommanded Product: tert-Butyl 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine-1-carboxylate, the main research area is biphenylpiperazine preparation radiolabeling PET imaging serotonin 5HT7 receptor; 5-HT(7) receptor; Arylpiperazine; PET; Radioligand; SB-269970.

In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, showed the best combination of affinity, selectivity, and lipophilicity, and was thus chosen for carbon-11 labeling and evaluation in pigs. After i.v. injection, compound I entered the pig brain and displayed reversible tracer kinetics. Pretreatment with the 5-HT7 receptor selective antagonist SB-269970 resulted in limited decrease in the binding of I, suggesting that this radioligand is not optimal for imaging the brain 5-HT7 receptor in vivo but it may serve as a lead compound for the design of novel 5-HT7 receptor PET radioligands.

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

Segawa, Jun’s team published research in Journal of Medicinal Chemistry in 1992-12-11 | CAS: 113028-17-4

Journal of Medicinal Chemistry published new progress about thiazetoquinolinecarboxylic acid derivative preparation bactericide. 113028-17-4 belongs to class piperazines, name is Ethyl 6-fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate, and the molecular formula is C18H20FN3O3S, Synthetic Route of 113028-17-4.

Segawa, Jun published the artcileStudies on pyridonecarboxylic acids. 1. Synthesis and antibacterial evaluation of 7-substituted-6-halo-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acids, Synthetic Route of 113028-17-4, the main research area is thiazetoquinolinecarboxylic acid derivative preparation bactericide.

A series of [1,3]thiazeto[3,2-a]quinoline-3-carboxylic acids (I) and their esters were prepared and evaluated for antibacterial activity. The derivatives with an H or Me group at C-1, F at C-6, and a piperazinyl or 4-methyl-1-piperazinyl group at C-7 showed superior in vitro antibacterial activity, and the derivatives with 4-methyl-1-piperazinyl group at C-7 had potent in vivo activity. I (R = piperazino) (NM394) showed excellent in vitro antibacterial activity and low toxicity but poor absorption from the gastrointestinal tract. I [R = (5-methyl-2-oxo-1,3-dioxol-4-yl)methylpiperazino) (NM441) had a favorable pharmacokinetic profile and oral activity superior to that of ciprofloxacin in exptl. animals.

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

Locatelli, Marcello’s team published research in Journal of Pharmaceutical and Biomedical Analysis in 2013-05-05 | CAS: 113028-17-4

Journal of Pharmaceutical and Biomedical Analysis published new progress about HPLC. 113028-17-4 belongs to class piperazines, name is Ethyl 6-fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate, and the molecular formula is C18H20FN3O3S, Synthetic Route of 113028-17-4.

Locatelli, Marcello published the artcileHigh performance liquid chromatography determination of prulifloxacin and five related impurities in pharmaceutical formulations, Synthetic Route of 113028-17-4, the main research area is prulifloxacin impurity determination HPLC tablet.

A novel HPLC method for the simultaneous determination of Prulifloxacin, Ulifloxacin, its process impurities in a tablets formulation and Enrofloxacin, used as Internal Standard, is developed. The separation was successfully carried out with a new stationary phase, HILIC, under isocratic elution mode using ammonium acetate buffer (5 mM, pH 5.8) and acetonitrile (12:88, volume/volume) at a flow rate of 1.0 mL/min. Column was thermostated at 25 °C (±1 °C) and 20 μL were injected for the anal. Calibration curves were linear in the investigated range with correlation coefficient better than 0.9880, while the limit of quantifications ranged from 0.25 to 5 μg/mL, depending from the analyte. The within and between batch precision (RSD%) values ranged from 0.11% to 13.9% while within and between batch trueness (bias%) values ranged from 14.0% to -11.3%. This method for the direct determination and quantification of process impurities in pharmaceutical formulations is suitable for routine analyses in quality control laboratories and was applied to evaluate for the 1st time, the presence and the quantities of cited analytes in com. available formulation.

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

Segawa, Jun’s team published research in Chemical & Pharmaceutical Bulletin in 1995-07-31 | CAS: 113028-17-4

Chemical & Pharmaceutical Bulletin published new progress about Crystal structure. 113028-17-4 belongs to class piperazines, name is Ethyl 6-fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate, and the molecular formula is C18H20FN3O3S, Product Details of C18H20FN3O3S.

Segawa, Jun published the artcileStudies on pyridonecarboxylic acids. IV. Synthesis and antibacterial activity evaluation of S-(-)- and R-(+)-6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acids, Product Details of C18H20FN3O3S, the main research area is thiazetoquinolinecarboxylic acid synthesis antibacterial activity.

Optically active isomers of 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid (NM394) were prepared through optical resolution of a racemic intermediate by high-performance liquid chromatog. The absolute configuration at the C-1 position in the thiazetoquinolone ring of the (-)-isomer was confirmed by X-ray anal. of to be S. The in vitro antibacterial activity of the (-)-isomer was 2-8 times that of the (+)-isomer.

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

Ozaki, Masakuni’s team published research in Chemotherapy (Basel) in 1998-02-28 | CAS: 113028-17-4

Chemotherapy (Basel) published new progress about Antimicrobial agents. 113028-17-4 belongs to class piperazines, name is Ethyl 6-fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate, and the molecular formula is C18H20FN3O3S, Recommanded Product: Ethyl 6-fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate.

Ozaki, Masakuni published the artcileIn vivo antibacterial activity of a prodrug of NM394, a thiazetoquinoline carboxylic acid derivative, Recommanded Product: Ethyl 6-fluoro-1-methyl-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-[1,3]thiazeto[3,2-a]quinoline-3-carboxylate, the main research area is thiazetoquinoline prodrug NM441 NM394 antibacterial.

NM394 (6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]-thiazeto[3,2-a]quinoline-3-carboxylic acid) has potent, broad-spectrum antibacterial activity in vitro, but not in vivo. To increase the bioavailability of NM394, various prodrugs were synthesized and tested. One of them, NM441, an N-(5-methyl-2-oxo-1,3-dioxol-4-yl) derivative, showed potent in vivo antibacterial activity. Using thin-layer chromatog.-bioautog., it was confirmed that after oral administration, NM441 was readily absorbed and hydrolyzed to NM394. Other prodrugs of NM394 were only partially metabolized to NM394. In pharmacokinetic studies in mice and monkeys, it was found that the blood levels of NM394 were 7.8 and 5.9 × greater, resp., when NM441 rather than NM394 was administered. These findings suggest that NM441 is an effective prodrug of NM394.

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