Month: November 2022

Floresca, Christina Z. published the artcileReciprocal mutations in TM2/TM3 in a D2 dopamine receptor background confirms the importance of this microdomain as a selective determinant of para-halogenated 1,4-disubstituted aromatic piperazines, COA of Formula: C18H19ClN4, the publication is Archiv der Pharmazie (Weinheim, Germany) (2005), 338(5-6), 268-275, database is CAplus and MEDLINE.

The authors recently demonstrated that in the D4 dopamine receptor the aromatic microdomain that spans the interface of the second and third transmembrane (TM) domains influences the high affinity interactions of extremely D4-selective ligands possessing a 1,4-disubstituted aromatic piperazine/piperidine (1,4-DAP) structure. On the basis of their substructural features and patterns of sensitivity to mutations constructed in a D4 receptor background, the D4-selective 1,4-DAPs were categorized as having two distinct modes of binding that the authors named mode-1 and mode-3. Here the authors extend these findings of the ligand-receptor structure-affinity relationships for some of these highly D4-selective 1,4-DAPs by measuring the effect of the corresponding reciprocal TM2/TM3 mutations constructed in a D2 dopamine receptor background on the binding affinity of the para-halogenated mode-1 ligands L750,667 and FAUC213. The results indicate that the D2-V2.61F+FV3.28-3.29LM mutant binds L750,667 and FAUC213 with significantly increased affinity, i.e., its binding profile becomes more D4-like. These findings further support the assignment of the TM2/TM3 aromatic microdomain encompassing positions 2.61 and 3.28-3.29 as a 1,4-DAP D4-selectivity microdomain and highlights the importance of the precise emplacement of aromatics in this microdomain as key to the selective mol. recognition of L750,667 and FAUC213.

Archiv der Pharmazie (Weinheim, Germany) 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, COA of Formula: C18H19ClN4.

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

Blass, Benjamin E. published the artcileDesign, synthesis, and evaluation of functionalized 5-(4-arylpiperazin-1-yl)-N-arylpentanamides as selective dopamine D₃ receptor ligands, Quality Control of 178928-58-0, the publication is Medicinal Chemistry Research (2022), 31(1), 132-145, database is CAplus.

Substance use disorder remains a major, unmet medical need. Cocaine is one of the most commonly abused recreational drugs and in 2018, there were over 5.5 million cocaine users. There are no approved therapies for the treatment of cocaine use disorder, but the D₃ dopamine receptor has been identified as a potential therapeutic target. Our initial lead compound (6) is a potent D₃ ligand with a high level of selectivity for D₃ over D2, but its solubility is low. We have identified a new series of functionalized 5-(4-arylpiperazin-1-yl)-N-arylpentanamides (7) that are potent D₃ binders that have moderate to high selectivity for D₃ over D₂. Exemplary members of this series were also significantly more soluble than our initial lead compound (6).

Medicinal Chemistry Research published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Quality Control of 178928-58-0.

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

Pagano, Mafalda published the artcileThe Fight against the Influenza A Virus H1N1: Synthesis, Molecular Modeling, and Biological Evaluation of Benzofurazan Derivatives as Viral RNA Polymerase Inhibitors, Application In Synthesis of 67914-60-7, the publication is ChemMedChem (2014), 9(1), 129-150, database is CAplus and MEDLINE.

The influenza RNA polymerase complex, which consists of the three subunits PA, PB1, and PB2, is a promising target for the development of new antiviral drugs. A large library of benzofurazan compounds was synthesized and assayed against influenza virus A/WSN/33 (H1N1). Most of the new derivatives were found to act by inhibiting the viral RNA polymerase complex through disruption of the complex formed between subunits PA and PB1. Docking studies were also performed to elucidate the binding mode of benzofurazans within the PB1 binding site in PA and to identify amino acids involved in their mechanism of action. The predicted binding pose is fully consistent with the biol. data and lays the foundation for the rational development of more effective PA-PB1 inhibitors.

ChemMedChem 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 In Synthesis of 67914-60-7.

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

Bordner, Jon published the artcile1,3-Diamino-6,7-dimethoxyisoquinoline derivatives as potential α₁-adrenoceptor antagonists, COA of Formula: C10H17N3O2, the publication is Journal of Medicinal Chemistry (1988), 31(5), 1036-9, database is CAplus and MEDLINE.

Treatment of 2,4,5-Me(MeO)₂C₆H₂CN (I) with LiN(CHMe₂)₂ followed by reaction with R₂NCN [R = Me, R₂ = (CH₂)₅] provided 1,3-diamino-6,7-dimethoxyisoquinolines II (R = as above), which were evaluated for α-adrenoceptor binding affinity and antihypertensive activity. II (R = Me) showed no significant affinity for α₁-adrenoceptors, while the 3-(2-furoyl-1-piperazinyl) analog III, prepared from I and 1-cyano-4-(tert-butoxycarbonyl)piperazine in 3 steps, was 1000-fold less potent than prazosin. PK_a data showed that 34% N(2) protonation of II (R = Me) (pK_a = 7.1) would occur at physiol. pH, in agreement with x-ray crystallog. anal. of III.HCl. Comparison of pos. charge distribution following protonation of II (R = Me) with the corresponding quinoline and quinazoline cations confirmed that N(1) protonation is required for these heterocyclic nuclei to bind efficiently to the α₁-adrenoceptor. Computer-assisted comparison of the x-ray structures of III.HCl and prazosin suggested that the 4.0 kcal/mol difference in α₁-adrenoceptor binding energies was largely due to salt-bridge formation (ca. 3.0 kcal/mol) between the protonated quinazoline and the receptor protein. Neither II nor III were effective antihypertensive agents in rats even when administered at relatively high doses (10 mg/kg). These results support the hypothesis that the antihypertensive activity of prazosin, doxazosin, and related compounds derives solely from α₁-adrenoceptor blocking.

Journal of Medicinal Chemistry published new progress about 113534-02-4. 113534-02-4 belongs to piperazines, auxiliary class Piperazine,Nitrile,Amide, name is tert-Butyl 4-cyanopiperazine-1-carboxylate, and the molecular formula is C10H17N3O2, COA of Formula: C10H17N3O2.

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

Silverman, Lisa S. published the artcile3H-[1,2,4]-Triazolo[5,1-i]purin-5-amine derivatives as adenosine A_2A antagonists, SDS of cas: 67914-60-7, the publication is Bioorganic & Medicinal Chemistry Letters (2007), 17(6), 1659-1662, database is CAplus and MEDLINE.

A novel series of 3-substituted-8-aryl-[1,2,4]triazolo[5,1-i]purin-5-amine analogs related to Sch 58261 was synthesized in order to identify potent adenosine A_2A receptor antagonists with improved selectivity over the A₁ receptor, physiochem. properties, and pharmacokinetic profiles as compared to those of Sch 58261. As a result of structural modifications, numerous analogs with excellent in vitro binding affinities and selectivities were identified. Moreover, compound I (R = MeOCH₂CH₂O) displayed both superior in vitro and highly promising in vivo profiles.

Bioorganic & Medicinal Chemistry Letters 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 C10H16Br3N, SDS of cas: 67914-60-7.

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

Yan, Zihong published the artcileSynthesis and antiviral activity evaluation of derivatives of anti-influenza virus inhibitor nucleozin, Computed Properties of 180698-19-5, the publication is Huaxue Tongbao (2018), 81(11), 1015-1022, database is CAplus.

Nucleozin has good inhibitory activity as an inhibitor against influenza virus nucleoprotein. In this paper, we investigate the aromatic ring part which is connected directly with piperazine in the nucleozin mol. structure. A series of nucleozin derivatives were synthesized by palladium catalyzed coupling reaction, and the structure-activity relationship of this part in nucleozin mol. was clarified by detecting the inhibitory activities of the synthesized compounds on influenza virus H1N1. After replacing the chlorine atom in the mol. with a Me group, it was found that the inhibitory activity is significantly improved compared with the prototype mol. nucleozin. This study has a significant meaning in the drug-like improvement of this kind of mol.

Huaxue Tongbao 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 C13H11NO, Computed Properties of 180698-19-5.

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

Gunsaru, Bornface published the artcileSimplified reversed chloroquines to overcome malaria resistance to quinoline-based drugs, Application of 1-Biphenyl-4-yl-piperazine, the publication is Antimicrobial Agents and Chemotherapy (2017), 61(5), e01913-16/1-e01913-16/13, database is CAplus and MEDLINE.

Building on our earlier work of attaching a chemosensitizer (reversal agent) to a known drug pharmacophore, we have now expanded the structure-activity relationship study to include simplified versions of the chemosensitizer. The change from two aromatic rings in this head group to a single ring does not appear to detrimentally affect the antimalarial activity of the compounds Data from in vitro heme binding and β-hematin inhibition assays suggest that the single aromatic RCQ compounds retain activities against Plasmodium falciparum similar to those of CQ, although other mechanisms of action may be relevant to their activities.

Antimicrobial Agents and Chemotherapy 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, Application of 1-Biphenyl-4-yl-piperazine.

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

Bryan, Marian C. published the artcilePyridones as Highly Selective, Noncovalent Inhibitors of T790M Double Mutants of EGFR, Application of 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, the publication is ACS Medicinal Chemistry Letters (2016), 7(1), 100-104, database is CAplus and MEDLINE.

The rapid advancement of a series of noncovalent inhibitors of T790M mutants of EGFR is discussed. The optimization of a nonselective high-throughput screening pyridone hit to potent mols. with high levels of selectivity over wtEGFR and the broader kinome is described herein.

ACS Medicinal Chemistry Letters published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C10H16N4, Application of 6-(4-Methylpiperazin-1-yl)pyridin-3-amine.

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

Leahy, James W. published the artcileDiscovery of a Novel Series of Potent and Orally Bioavailable Phosphoinositide 3-Kinase γ Inhibitors, HPLC of Formula: 1033743-83-7, the publication is Journal of Medicinal Chemistry (2012), 55(11), 5467-5482, database is CAplus and MEDLINE.

The phosphoinositide 3-kinases (PI3Ks) have been linked to an extraordinarily diversified group of cellular functions making these enzymes compelling targets for the treatment of disease. A large body of evidence has linked PI3Kγ to the modulation of autoimmune and inflammatory processes making it an intriguing target for drug discovery. A high-throughput screening (HTS) campaign revealed two hits that were nominated for further optimization studies. The in vitro activity of the first HTS hit, I, designated as the sulfonylpiperazine scaffold, was optimized utilizing structure-based design. However, nonoptimal pharmacokinetic properties precluded this series from further studies. An overlay of the x-ray structures of the sulfonylpiperazine scaffold and the second HTS hit, II, within their complexes with PI3Kγ revealed a high degree of overlap. This feature was utilized to design a series of hybrid analogs including advanced leads such as III with desirable potency, selectivity, and oral bioavailability.

Journal of Medicinal Chemistry published new progress about 1033743-83-7. 1033743-83-7 belongs to piperazines, auxiliary class Piperazine,Boronic acid and ester,Sulfamide,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester, name is tert-Butyl 4-((3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine-1-carboxylate, and the molecular formula is C21H33BN2O6S, HPLC of Formula: 1033743-83-7.

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

Belfield, Andrew J. published the artcileSynthesis of Meta-substituted aniline derivatives by nucleophilic substitution, Synthetic Route of 178928-58-0, the publication is Tetrahedron (1999), 55(46), 13285-13300, database is CAplus.

Substitution by amines of fluorobenzenes containing a meta-substituted electron withdrawing group (EWG), in DMSO at 100°C over 60 h gave meta-substituted aniline derivatives in isolated yields of up to 98%. The scope of the reaction is explored in terms of reaction conditions and substrates. It is postulated that facile meta-substitutions are facilitated through field stabilization of the intermediate anion by EWG substituents.

Tetrahedron published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Synthetic Route of 178928-58-0.

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