Month: November 2022

Ryu, Jae Chun published the artcileSynthesis of ketoconazole derivatives, Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, the publication is Bulletin of the Korean Chemical Society (2003), 24(4), 460-466, database is CAplus.

For the drug master file (DMF) of ketoconazole, four impurities contained in ketoconazole were synthesized. During the synthesis of I, a new synthetic method of 1,4-dihydropyrazine was established. To oxidize the aminoalc. of I to the aminal I, the standard Swern oxidation condition was modified to mask the nucleophilicity of the amino group temporarily using one equivalent of acetic acid. Derivative II was synthesized via regioselective bromination at the I position of the 4-aminophenol derivative of II using Br₂ in the presence of p-TsOH. The etherification of aryl bromide with a phenol derivative compound was accomplished by a modification of the general Cu-mediated reaction condition using excess of the phenol derivative itself as a solvent at elevated temperature (190 °C).

Bulletin of the Korean Chemical 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, Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone.

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

Boeckler, Frank published the artcileModeling the Similarity and Divergence of Dopamine D₂-like Receptors and Identification of Validated Ligand-Receptor Complexes, Quality Control of 337972-47-1, the publication is Journal of Medicinal Chemistry (2005), 48(3), 694-709, database is CAplus and MEDLINE.

Focusing on the similarity and divergence of GPCR subtypes and their ligand interactions, we generated dopamine D₂, D₃, and D₄ receptor models based on the rhodopsin crystal structure and refined these with an extensive MM/MD protocol. After validation by diagnostic exptl. data, subtype-specific relative positions of TM1, 2, 6, and 7 and bending angles of TM7 were found. To sample the conformational space of the complex, we performed simulated-annealing runs of the receptor protein with the sub-nanomolar antagonist spiperone. Docking a representative set of ligands, we were able to identify one superior model for each subtype when excellent correlations between predicted energies of binding and exptl. affinities (r² = 0.72 for D₂, 0.91 for D₃ and 0.77 for D₄) could be observed Further anal. revealed general ligand interactions with ASP3.32 and aromatic residues in TM6/7 and individual key interactions with TM1 and TM2 residues of the D₃ and D₄ receptor models, resp.

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, Quality Control of 337972-47-1.

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

Sun, Jun-Rong published the artcile3D-QSAR and docking studies on pyrrolopyrimidine derivatives as LIM-kinase 2 inhibitors, Computed Properties of 1116571-01-7, the publication is Letters in Drug Design & Discovery (2011), 8(3), 229-240, database is CAplus.

The pyrrolopyrimidine derivatives have been regarded as a novel class of LIM-kinase 2 inhibitor. To explore the relationship between the structures of substituted pyrrolopyrimidine derivatives and their inhibitory activities against LIMK2, CoMFA and CoMSIA analyses, and mol. docking studies were performed on a dataset of forty-one compounds The two 3D-QSAR models resulted from thirty-one mols. in the training set gave r²_cv values of 0.635 and 0.660, r² values of 0.973 and 0.965, resp. The predictive ability of CoMFA and CoMSIA, determined using a test set of ten compounds, gave predictive correlation coefficients of 0.971 and 0.964, resp. 3D contour maps generated from CoMFA and CoMSIA along with the docking binding structures provided enough information about the structural requirements for better activity. The results can serve as a useful guideline to design novel LIMK2 inhibitors with better potencies.

Letters in Drug Design & Discovery 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 C12H14BNO2, Computed Properties of 1116571-01-7.

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

Morera, Ludovica published the artcileDevelopment and characterization of endocannabinoid hydrolases FAAH and MAGL inhibitors bearing a benzotriazol-1-yl carboxamide scaffold, Category: piperazines, the publication is Bioorganic & Medicinal Chemistry (2012), 20(21), 6260-6275, database is CAplus and MEDLINE.

A series of (1H-benzo[d][1,2,3]triazol-1-yl)(4-benzylpiperazin-1-yl)methanones and of (1H-benzo[d][1,2,3]triazol-1-yl)(4-phenylpiperazin-1-yl)methanones has been prepared and tested on human fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). In the benzylpiperazinyl series, compound 29 (ML30) exhibited an IC₅₀ value of 0.54 nM on MAGL, combined with a 1000-fold selectivity vs. FAAH, while compounds 11 and 16 acted as potent dual FAAH-MAGL inhibitors (IC₅₀ <10 nM). In the phenylpiperazinyl series, compounds 37, 38, 42, and 43 displayed IC₅₀ values against MAGL in the nanomolar range, while being between one and two orders of magnitude less potent on the FAAH, while compounds 31 and 32 were potent FAAH inhibitors (IC₅₀ <20 nM) and over 12-fold selective vs. MAGL. The key structural determinants driving the structure-activity relationships were explored by the minimization of the inhibitors inside the active site of both enzymes.

Bioorganic & Medicinal Chemistry 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, Category: piperazines.

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

Fukunishi, Yoshifumi published the artcilePrediction of Synthetic Accessibility Based on Commercially Available Compound Databases, Name: N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, the publication is Journal of Chemical Information and Modeling (2014), 54(12), 3259-3267, database is CAplus and MEDLINE.

A compound’s synthetic accessibility (SA) is an important aspect of drug design, since in some cases computer-designed compounds cannot be synthesized. There have been several reports on SA prediction, most of which have focused on the difficulties of synthetic reactions based on retro-synthesis analyses, reaction databases and the availability of starting materials. The authors developed a new method of predicting SA using com. available compound databases and mol. descriptors. SA was estimated from the probability of existence of substructures consisting of the compound in question, the number of symmetry atoms, the graph complexity, and the number of chiral centers of the compound The probabilities of the existence of given substructures were estimated based on a compound library. The predicted SA results reproduced the expert manual assessments with a Pearson correlation coefficient of 0.56. Since the authors method required a compound database and not a reaction database, it should be easy to customize the prediction for compound vendors. The correlation between the sales price of approved drugs and the SA values was also examined and weak. The price most likely depends on the total cost of development and other factors.

Journal of Chemical Information and Modeling published new progress about 863127-77-9. 863127-77-9 belongs to piperazines, auxiliary class TGF-beta/Smad,Bcr-Abl,Natural product, name is N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, and the molecular formula is C22H28ClN7O3S, Name: N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate.

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

Mastuo, Kasumi published the artcileNickel-Catalyzed Hydrodeoxygenation of Aryl Sulfamates with Alcohols as Mild Reducing Agents, Product Details of C12H16N2O2, the publication is Synthesis (2021), 53(23), 4449-4460, database is CAplus.

The nickel-catalyzed hydrodeoxygenation of aryl sulfamates ROS(O)₂R¹ [R = 2-propanoylbenzen-1-yl, 1-ethyl-1H-indol-4-yl, 4-(4-acetylpiperazin-1-yl)benzen-1-yl, etc.; R¹ = dimethylaminyl, piperidin-1-yl, bis(propan-2-yl)aminyl, etc.] has been developed with alcs. as mild reductants. A variety of functional groups and heterocycles were tolerated in this reaction system to give the desired products RH in high yields. In addition, the gram-scale process and stepwise cine-substitution were also achieved with high efficiency.

Synthesis 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

Khan, Mohammad Faheem published the artcileSynthesis of novel imbricatolic acid analogues via insertion of N-substituted piperazine at C-15/C-19 positions, displaying glucose uptake stimulation in L6 skeletal muscle cells, Name: (E)-1-Cinnamylpiperazine, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(14), 4636-4639, database is CAplus and MEDLINE.

A new class of N-substituted piperazine analogs of imbricatolic acid have been designed and synthesized by using the appropriate synthetic routes in excellent yield. All synthesized compounds were screened for their in vitro glucose uptake stimulatory activity. Among them compounds I–IV triggered L6 skeletal muscle cells for glucose uptake at 54.73%, 40.79%, 40.90%, and 39.55% stimulation, resp. I has emerged as important lead compound showing potential antidiabetic activity. Illustration about their synthesis and in vitro glucose uptake activity is described.

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, Name: (E)-1-Cinnamylpiperazine.

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

Kuriyama, Masami published the artcileNickel-Catalyzed Deoxygenative Deuteration of Aryl Sulfamates, Quality Control of 67914-60-7, the publication is Advanced Synthesis & Catalysis (2017), 359(6), 1043-1048, database is CAplus.

The nickel-catalyzed deoxygenative deuteration of aryl/heteroaryl sulfamates was developed, and the effective incorporation of deuterium into a variety of aromatic compounds was achieved with sufficient catalytic efficiency and high deuteration degree. This process tolerated reducible functional moieties and heterocyclic structures. Addnl., a double introduction of deuterium also successfully gave a desired product with a high yield and deuterium content.

Advanced Synthesis & Catalysis 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

Severinsen, Kasper published the artcileBinding of the Amphetamine-like 1-Phenyl-piperazine to Monoamine Transporters, Recommanded Product: 1-Biphenyl-4-yl-piperazine, the publication is ACS Chemical Neuroscience (2012), 3(9), 693-705, database is CAplus and MEDLINE.

The human serotonin transporter (hSERT), the human dopamine transporter (hDAT), and the human norepinephrine transporter (hNET) facilitate the active uptake of the neurotransmitters serotonin, dopamine, and norepinephrine from the synaptic cleft. Drugs of abuse such as MDMA (street-name ecstasy) and certain 1-phenyl-piperazine (PP) analogs such as 1-(3-chlorophenyl)-piperazine (mCPP) elicit their stimulatory effect by elevating the synaptic concentration of serotonin by blocking or reversing the normal transport activity of hSERT. Recent data suggest that certain analogs of PP may be able to counteract the addictive effect of cocaine. Little is still known about the precise mechanism by which MDMA and PP analogs function at hSERT, hDAT, and hNET and even less is known about the specific protein-ligand interactions. In this study, we provide a comprehensive biochem. examination of a repertoire of PP analogs in hSERT, hDAT, and hNET. Combined with induced fit docking models and mol. dynamics simulations of PP and 1-(3-hydroxyphenyl)-piperazine (3-OH-PP) bound to hSERT and hDAT, we present detailed mol. insight into the promiscuous binding of PP analogs in the monoamine transporters. We find that PP analogs inhibit uptake as well as induce release in all three monoamine transporters. We also find that the selectivity of the PP analogs can be adjusted by carefully selecting substituents on the PP skeleton.

ACS Chemical Neuroscience 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 C5H10N2OS, Recommanded Product: 1-Biphenyl-4-yl-piperazine.

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

Hou, Jinqiang published the artcileDevelopment of Candidates for Positron Emission Tomography (PET) Imaging of Ghrelin Receptor in Disease: Design, Synthesis, and Evaluation of Fluorine-Bearing Quinazolinone Derivatives, Computed Properties of 67914-60-7, the publication is Journal of Medicinal Chemistry (2018), 61(3), 1261-1275, database is CAplus and MEDLINE.

Mol. imaging with positron emission tomog. (PET) is an attractive platform for noninvasive detection and assessment of disease. The development of a PET imaging agent targeting the ghrelin receptor (growth hormone secretagogue receptor type 1a or GHS-R1a) has the potential to lead to the detection and assessment of the higher than normal expression of GHS-R1a in diseases such as prostate, breast, and ovarian cancer. To enable the development of ¹⁸F radiopharmaceuticals, we have designed and synthesized three series of quinazolinone derivatives, resulting in the identification of two compound with subnanomolar binding affinity and one fluorine-bearing compound I with picomolar binding affinity (20 pM), representing the highest binding affinity for GHS-R1a reported to date. Two lead compounds (II, IC₅₀ = 20.6 nM; III, IC₅₀ = 9.3 nM) were successfully ¹⁸F-radiolabeled with radiochem. purity of greater than 99%. Mol. modeling studies were performed to shed light on ligand-receptor interactions.

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, Computed Properties of 67914-60-7.

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