M.W=200-250 | Page 24 of 29 | Heterocyclic Building Blocks-piperazine

Johnson, Mark’s team published research in Journal of Medicinal Chemistry in 56 | CAS: 945953-41-3

Journal of Medicinal Chemistry published new progress about 945953-41-3. 945953-41-3 belongs to piperazines, auxiliary class Piperazine,Amide,Aldehyde, name is tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, and the molecular formula is C11H20N2O3, Recommanded Product: tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate.

Johnson, Mark published the artcileStructure-Activity Relationship Study of N⁶-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N⁶-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine Analogues: Development of Highly Selective D3 Dopamine Receptor Agonists along with a Highly Potent D2/D3 Agonist and Their Pharmacological Characterization [Erratum to document cited in CA157:094154], Recommanded Product: tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, the publication is Journal of Medicinal Chemistry (2013), 56(2), 589-590, database is CAplus and MEDLINE.

On page 5826, the abstract contained an incorrect structure; the corrected structure is given. On page 5828, Scheme 2 contained several incorrect structures; the corrected scheme is given. Corrected elemental anal. and mass spectrometry data are given for the Supporting Information and Table 1.

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

Modi, Gyan’s team published research in Journal of Medicinal Chemistry in 57 | CAS: 180698-19-5

Journal of Medicinal Chemistry 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, Related Products of piperazines.

Modi, Gyan published the artcileStructural Modifications of Neuroprotective Anti-Parkinsonian (-)-N6-(2-(4-(Biphenyl-4-yl)piperazin-1-yl)-ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine (D-264): An Effort toward the Improvement of in Vivo Efficacy of the Parent Molecule, Related Products of piperazines, the publication is Journal of Medicinal Chemistry (2014), 57(4), 1557-1572, database is CAplus and MEDLINE.

In our overall goal to develop multifunctional dopamine D₂/D₃ agonist drugs for the treatment of Parkinson’s disease (PD), we previously synthesized potent D₃ preferring agonist D-264 (1a), which exhibited neuroprotective properties in two animal models of PD. To enhance the in vivo efficacy of 1a, a structure-activity relationship study was carried out. Competitive binding and [³⁵S]GTPγS functional assays identified compound (-)-9b as one of the lead mols. with preferential D₃ agonist activity (EC₅₀(GTPγS); D₃ = 0.10 nM; D₂/D₃ (EC₅₀): 159). Compounds (-)-9b and (-)-8b exhibited high in vivo activity in two PD animal models, reserpinized and 6-hydroxydopamine (OHDA)-induced unilateral lesioned rats. On the other hand, 1a failed to show any in vivo activity in these models unless the compound was dissolved in 5-10% beta-hydroxy Pr cyclodextrin solution Lead compounds exhibited appreciable radical scavenging activity. In vitro experiments with dopaminergic MN9D cells indicated neuroprotection by both 1a and (-)-9b from toxicity of MPP+.

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

Meddad-Belhabich, Nadia’s team published research in Bioorganic & Medicinal Chemistry in 18 | CAS: 67914-60-7

Bioorganic & 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, Computed Properties of 67914-60-7.

Meddad-Belhabich, Nadia published the artcileDesign of new potent and selective secretory phospholipase A₂ inhibitors. 6-Synthesis, structure-activity relationships and molecular modelling of 1-substituted-4-[4,5-dihydro-1,2,4-(4H)-oxadiazol-5-one-3-yl(methyl)]-functionalized aryl piperazin/one/dione derivatives, Computed Properties of 67914-60-7, the publication is Bioorganic & Medicinal Chemistry (2010), 18(10), 3588-3600, database is CAplus and MEDLINE.

The group IIA human non-pancreatic secretory phospholipase A₂ (hnp-sPLA₂) is one of the enzymes implied in the inflammatory process. In the course of our work on inhibitors of this enzyme we investigated the influence of rigidity of the piperazine region on the biol. activity. Several modifications were explored. Various linkers, such as amide, urea, carbamate, or alkoxyphenyl were inserted between the piperazine and the lipophilic chain. Also, modification of the piperazine core to incorporate carbonyl groups was studied. In an in vitro fluorimetric assay using the human GIIA (HPLA₂) and porcine pancreatic GIB enzymes, compound 60a (I) had the optimal activity with an IC₅₀ = 30 nM on HPLA₂. By means of mol. modeling we attempted to get informations towards comprehension of differences in activity.

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

Stefancich, Giorgio’s team published research in Archiv der Pharmazie (Weinheim, Germany) in 325 | CAS: 67914-60-7

Archiv der Pharmazie (Weinheim, Germany) 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 C7H7IN2O, SDS of cas: 67914-60-7.

Stefancich, Giorgio published the artcileAntibacterial and antifungal agents. XV. Synthesis and antifungal activity of structural analogs of bifonazole and ketoconazole, SDS of cas: 67914-60-7, the publication is Archiv der Pharmazie (Weinheim, Germany) (1992), 325(11), 687-94, database is CAplus and MEDLINE.

The synthesis and antifungal activities of the cis– and trans-1-acetyl-4-{4-[[2-(1,1′-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl}piperazines I are reported. Stereochem. assignments to diastereomeric pairs of cis/trans isomers were made on the basis of ¹H and ¹³C NMR data. Among test derivatives the best activity was shown by the benzoyl esters of the cis– and trans-[2-(1,1′-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methanols II (R = H, SO₂CH₃).

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

Goodarzi, Hassan’s team published research in Journal of the Electrochemical Society in 165 | CAS: 67914-60-7

Journal of the Electrochemical Society 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.

Goodarzi, Hassan published the artcileElectrochemical Synthesis of a New Derivative of 1,4-Dihydroxybenzene: Embedded Nucleophile in the Structure of Electrophile, SDS of cas: 67914-60-7, the publication is Journal of the Electrochemical Society (2018), 165(10), H667-H672, database is CAplus.

The electrochem. oxidation of 4-(Piperazin-1-yl)phenols (1a,b) was studied in the H₂O, MeCN and nitromethan by cyclic voltammetry and controlled-potential coulometry. P-quinone-imines generated of oxidation 4-(Piperazin-1-yl)phenols after the hydrolysis reaction participate in Michael-addition reactions with released piperazine of hydrolysis reaction of p-quinone imines. The present work led to the development of a facile and environmentally friendly electrochem. method for the synthesis of a new derivative of 1,4-dihydroxybenzene under green conditions. The effect of H₂O as a solute on the electrochem. response of 4-(Piperazin-1-yl)phenols (1a,b) was examined in the MeCN (AN) and nitromethane (NM) solvent.

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

Heeres, J.’s team published research in Journal of Medicinal Chemistry in 27 | CAS: 67914-60-7

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, Category: piperazines.

Heeres, J. published the artcileAntimycotic azoles. 7. Synthesis and antifungal properties of a series of novel triazol-3-ones, Category: piperazines, the publication is Journal of Medicinal Chemistry (1984), 27(7), 894-900, database is CAplus and MEDLINE.

The antifungal triazolone derivatives I [R = H, Me, Q (X = N, CH); R¹ = H, alkyl; R² = H, Me) were prepared by a multistep sequence from 1-(p-methoxyphenyl)piperazine or MeSO₃Q via piperazines III (R³ = H, Bz) and cyclization of III [R³ = C(:NH)NH₂] with R²C(:NH)NH₂. In vitro and in vivo antifungal properties of I are reported. Compound I [R = Q (X = N), R¹ = MeEtCH, R² = H], which displays a pronounced oral activity against vaginal candidosis in rats and against microsporosis in guinea pigs, was selected for clin. evaluation.

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

He, Chunxian’s team published research in ChemMedChem in 2017 | 229009-40-9

ChemMedChem published new progress about ATPase inhibitors. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Synthetic Route of 229009-40-9.

He, Chunxian; Preiss, Laura; Wang, Bin; Fu, Lei; Wen, Hui; Zhang, Xiang; Cui, Huaqing; Meier, Thomas; Yin, Dali published the artcile< Structural Simplification of Bedaquiline: the Discovery of 3-(4-(N,N-Dimethylaminomethyl)phenyl)quinoline-Derived Antitubercular Lead Compounds>, Synthetic Route of 229009-40-9, the main research area is quinoline dimethylaminomethyl phenyl preparation antitubercular activity; ATP synthase; Mycobacterium tuberculosis; bedaquiline; multidrug resistance; pulmonary tuberculosis.

Bedaquiline (BDQ) is a novel and highly potent last-line antituberculosis drug that was approved by the US FDA in 2013. Owing to its stereo-structural complexity, chem. synthesis and compound optimization are rather difficult and expensive. This study describes the structural simplification of bedaquiline while preserving antitubercular activity. The compound’s structure was split into fragments and reassembled in various combinations while replacing the two chiral carbon atoms with an achiral linkage instead. Four series of analogs were designed; these candidates retained their potent antitubercular activity at sub-microgram per mL concentrations against both sensitive and multidrug-resistant (MDR) Mycobacterium tuberculosis strains. Six out of the top nine MIC-ranked candidates were found to inhibit mycobacterial ATP synthesis activity with IC50 values between 20 and 40 μm, one had IC50>66 μm, and two showed no inhibition, despite their antitubercular activity. These results provide a basis for the development of chem. less complex, lower-cost bedaquiline derivatives and describe the identification of two derivatives with antitubercular activity against non-ATP synthase related targets.

ChemMedChem published new progress about ATPase inhibitors. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Synthetic Route of 229009-40-9.

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

Zhou, Min’s team published research in Journal of the American Chemical Society in 2018-06-06 | 229009-40-9

Journal of the American Chemical Society published new progress about Alkynes, arynes Role: RCT (Reactant), RACT (Reactant or Reagent). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Application In Synthesis of 229009-40-9.

Zhou, Min; Ni, Chuanfa; Zeng, Yuwen; Hu, Jinbo published the artcile< Trifluoromethyl Benzoate: A Versatile Trifluoromethoxylation Reagent>, Application In Synthesis of 229009-40-9, the main research area is trifluoromethyl benzoate versatile trifluoromethoxylation reagent; trifluoromethoxylation halogenation aryne.

Trifluoromethyl benzoate (TFBz) is developed as a new shelf-stable trifluoromethoxylation reagent, which can be easily prepared from inexpensive starting materials using KF as the only fluorine source. The synthetic potency of TFBz is demonstrated by trifluoromethoxylation-halogenation of arynes, nucleophilic substitution of alkyl (pseudo)halides, cross-coupling with aryl stannanes, and asym. difunctionalization of alkenes. The unprecedented trifluoromethoxylation-halogenation of arynes proceeds smoothly at room temperature with the aid of a crown ether-complexed potassium cation, which significantly stabilizes the trifluoromethoxide anion derived from TFBz.

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

Ivashchenko, Andrey A’s team published research in Bioorganic & Medicinal Chemistry in 2020-10-15 | 229009-40-9

Bioorganic & Medicinal Chemistry published new progress about Alkadiynes Role: PAC (Pharmacological Activity), PKT (Pharmacokinetics), PRP (Properties), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

Ivashchenko, Andrey A.; Ivanenkov, Yan A.; Aladinskiy, Vladimir A.; Karapetian, Ruben N.; Koryakova, Angela G.; Ryakhovskiy, Alexey A.; Mitkin, Oleg D.; Kravchenko, Dmitry V.; Savchuk, Nikolai P.; Zagribelnyy, Bogdan A.; Ivashchenko, Alexander V. published the artcile< Synthesis, biological evaluation and in silico modeling of novel pan-genotypic NS5A inhibitors>, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is peptide linked bisimidazole preparation NS5A inhibitor mol modeling SAR; Combinatorial synthesis; HCV; In silico modeling; Medicinal chemistry; NS5A inhibitors.

A series of novel small-mol. pan-genotypic hepatitis C virus (HCV) NS5A inhibitors with picomolar activity containing 2-[(2S)-pyrrolidin-2-yl]-5-[4-(4-{2-[(2S)-pyrrolidin-2-yl]-1H-imidazol-5-yl}buta-1,3-diyn-1-yl)aryl]-1H-imidazole core was designed based on mol. modeling study and SAR anal. The constructed in silico model and docking study provide a deep insight into the binding mode of this type of NS5A inhibitors. Based on the predicted binding interface authors have prioritized the most crucial diversity points responsible for improving antiviral activity. The synthesized mols. were tested in a cell-based assay, and compound I exhibited an EC50 value in the range of 2.9-34 pM against six genotypes of NS5A HCV, including gT3a, and demonstrated favorable pharmacokinetic profile in rats. This lead compound can be considered as an attractive candidate for further clin. evaluation.

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

Liu, Xuesong’s team published research in Journal of Medicinal Chemistry in 2019-05-23 | 229009-40-9

Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Reference of 229009-40-9.

Liu, Xuesong; Wang, Beilei; Chen, Cheng; Qi, Ziping; Zou, Fengming; Wang, Junjie; Hu, Chen; Wang, Aoli; Ge, Juan; Liu, Qingwang; Yu, Kailin; Hu, Zhenquan; Jiang, Zongru; Wang, Wei; Wang, Li; Wang, Wenchao; Ren, Tao; Bai, Mingfeng; Liu, Qingsong; Liu, Jing published the artcile< Discovery of (E)-N1-(3-Fluorophenyl)-N3-(3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)malonamide (CHMFL-KIT-033) as a Novel c-KIT T670I Mutant Selective Kinase Inhibitor for Gastrointestinal Stromal Tumors (GISTs)>, Reference of 229009-40-9, the main research area is CHMFL KIT033 preparation cKIT T670I kinase inhibitor gastrointestinal tumor.

Gain-of-function mutations of c-KIT kinase play crucial pathol. roles for the gastrointestinal stromal tumors (GISTs). Despite the success of imatinib as the first-line treatment of GISTs, dozens of drug-acquired resistant mutations emerge, and c-KIT T670I is one of the most common mutants among them. Although several kinase inhibitors are capable of overcoming the T670I mutant, none of them can achieve the selectivity over the c-KIT wild-type (wt), which also plays important roles in a variety of physiol. functions such as hematopoiesis. Starting from axitinib, through fragment hybrid type II kinase inhibitor design approach, we have discovered a novel inhibitor 24, which not only exhibits potent activity to c-KIT T670I mutant but also achieves 12-fold selectivity over c-KIT weight Compound 24 displays good antiproliferative effects against c-KIT T670I mutant-driven GIST cell lines (GIST-T1/T670I and GIST-5R) and also exhibits suitable in vivo pharmacokinetic profiles as well as dose-dependent antitumor efficacy. This study provides a proof of concept for developing a c-KIT mutant selective inhibitor that theor. can render a better therapeutic window.

Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Reference of 229009-40-9.

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