Category: piperazines

Stewart, Andrew O. published the artcileDopamine D₄ ligands and models of receptor activation: 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole and related heteroarylmethylarylpiperazines exhibit a substituent effect responsible for additional efficacy tuning, Formula: C18H19ClN4, the publication is Journal of Medicinal Chemistry (2004), 47(9), 2348-2355, database is CAplus and MEDLINE.

A series of subtype selective dopamine D₄ receptor ligands from the heteroarylmethylphenylpiperazine class have been discovered that exhibit a remarkable structure-activity relation (SAR), revealing a substituent effect in which regiosubstitution on the terminal arylpiperazine ring can modulate functional or intrinsic activity. Other structure-dependent efficacy studies in the dopamine D₄ field have suggested a critical interaction of the heteroarylmethyl moiety with specific protein microdomains in controlling intrinsic activity. The authors studies indicate that for some binding orientations, the phenylpiperazine moiety also plays a key role in determining efficacy. These data also implicate a kinetic or efficiency term, contained within measured functional affinities for agonists, which support a sequential binding and conformational stabilization model for receptor activation. The structural similarity between partial agonist and antagonist, within this subset of ligands, and lack of bioisosterism for this substituent effect are key phenomena for these hypotheses.

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 C16H20N2, Formula: C18H19ClN4.

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

Zhang, Chenghong published the artcileStrategies to Mitigate the Bioactivation of Aryl Amines, Category: piperazines, the publication is Chemical Research in Toxicology (2020), 33(7), 1950-1959, database is CAplus and MEDLINE.

The bioactivation of xenobiotics to yield reactive metabolites can lead to tolerability and toxicity concerns within a drug discovery program. Development of strategies for mitigating the metabolic liability of commonly encountered toxicophores, such as anilines, relies on an understanding of the relative tendency of these functionalities to undergo bioactivation. In this report, we present the first systematic study of the structure-activity relationships of the bioactivation of aryl amine fragments (mol. weight < 250 Da) using a glutathione (GSH) trapping assay in the presence of human liver microsomes and the reduced form of NADP. This study demonstrates that conversion of anilines to nitrogen-containing heteroarylamines results in a lower abundance of GSH conjugates in the order Ph > pyrimidine ≈ pyridine > pyridazine. Introduction of electron-withdrawing functionality on the aromatic ring had a less pronounced effect on the extent of GSH conjugation. Examination of more drug-like compounds sourced from inhouse drug discovery programs revealed similar trends in bioactivation between matched pairs containing (hetero)aryl amines. This study provides medicinal chemists with insights and qual. guidance for the minimization of risks related to aryl amine metabolism

Chemical Research in Toxicology 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 C20H32B2O4, Category: piperazines.

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

Capuano, Ben published the artcileSynthesis and Preliminary Pharmacological Evaluation of 4′-Arylalkyl Analogs of Clozapine. III. Replacement of the Tricyclic Nucleus with a Bicyclic Template, SDS of cas: 87179-40-6, the publication is Australian Journal of Chemistry (2007), 60(12), 928-933, database is CAplus.

As a continuing part of our research program in search of novel compounds for the treatment of schizophrenia, we report the synthesis and preliminary receptor binding affinity for a series of bicyclic analogs of clozapine [I; Y = CH₂, Z = H, 3,4-OCH₂O, 3-OMe, 4-OMe; Y = CH₂CH₂, (CH₂)₃, (E)-CH:CHCH₂, Z = H] derived from a selection of promising tricyclic candidates published previously. These bicyclic compounds investigate some substituent effects and the length and nature of the linker between an ionizable nitrogen atom at physiol. pH and the introduced aryl moiety. The chem., structural characterization, and in vitro evaluation are described. Preliminary findings on the effects on activity of the nature and length of the linker, degree of unsaturation, and selected substituents coupled to the bicyclic nucleus are discussed in relation to affinity for dopamine D₄ and serotonin 5-HT_2A receptors.

Australian Journal of 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, SDS of cas: 87179-40-6.

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

Capuano, Ben published the artcileSynthesis and Preliminary Pharmacological Evaluation of 4′-Arylalkyl Analogues of Clozapine. II. Effect of the Nature and Length of the Linker, Computed Properties of 87179-40-6, the publication is Australian Journal of Chemistry (2003), 56(9), 875-886, database is CAplus.

We report the synthesis of a second generation of tricyclic analogs of clozapine, investigating the length and nature of the chain between an ionizable nitrogen atom at physiol. pH and the introduced aryl moiety. The chem., structural characterization, and pharmacol. evaluation of this series of 4′-arylalkyl analogs of clozapine are described. Preliminary findings on the effects on activity of the nature and length of the linker, degree of unsaturation, and type of aryl moiety on blockade of dopamine D₄ and serotonin 5-HT_2A receptors are discussed and animal behavioral data for key compounds presented.

Australian Journal of 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, Computed Properties of 87179-40-6.

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

Ericksen, Spencer S. published the artcileLigand selectivity of D₂ dopamine receptors is modulated by changes in local dynamics produced by sodium binding, COA of Formula: C18H19ClN4, the publication is Journal of Pharmacology and Experimental Therapeutics (2009), 328(1), 40-54, database is CAplus and MEDLINE.

We have uncovered a significant allosteric response of the D₂ dopamine receptor to physiol. relevant concentrations of sodium (140 mM), characterized by a sodium-enhanced binding affinity for a D₄-selective class of agonists and antagonists. This enhancement is significantly more pronounced in a D₂-V2.61(91)F mutant and cannot be mimicked by an equivalent concentration of the sodium replacement cation N-methyl-D-glucamine. This phenomenon was explored computationally at the mol. level by analyzing the effect of sodium binding on the dynamic properties of D₂ receptor model constructs. Normal mode anal. identified one mode (M₁₉), which is involved in the open/closed motions of the binding cleft as being particularly sensitive to the sodium effect. To examine the consequences for D₂ receptor ligand recognition, one of the ligands, L-745,870 [3-{[4-(4-chlorophenyl) piperazin-1-yl]methyl}-1H-pyrrolo[2,3-b]pyridine or CPPMA, chlorophenylpiperazinyl methylazaindole], was docked into conformers along the M₁₉ trajectory. Structurally and pharmacol. well established ligand-receptor interactions, including the ionic interaction with D3.32(114) and interactions between the ligand aryl moieties and V2.61(91)F, were achieved only in “open” phase conformers. The docking of (-)-raclopride [3,5-dichloro-N-(1-ethylpyrrolidin-2-ylmethyl)-2-hydroxy-6-methoxybenzamide] suggests that the same binding cleft changes in response to sodium-binding perturbation account as well for the enhancements in binding affinity for substituted benzamides in the wild-type D₂ receptor. Our findings demonstrate how key interactions can be modulated by occupancy at an allosteric site and are consistent with a mechanism in which sodium binding enhances the affinity of selected ligands through dynamic changes that increase accessibility of substituted benzamides and 1,4-DAP ligands to the orthosteric site and accessibility of 1,4-DAPs to V2.61(91)F.

Journal of Pharmacology and Experimental Therapeutics 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

Cremonesi, Giuseppe published the artcileLewis acid-catalyzed formylation reaction of 4-(piperazin-1-yl)phenols, SDS of cas: 67914-60-7, the publication is Heterocycles (2014), 88(1), 603-606, database is CAplus.

The Lewis acid-catalyzed reaction of 4-(piperazin-1-yl)phenols I (R¹ = Ac, CHO, Boc, PhCH₂; R² = H) with paraformaldehyde in aprotic solvents afforded salicylaldehydes I (R² = CHO) in good yields.

Heterocycles 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.

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

Crespo, Roberto A. published the artcileStructure-Guided Drug Design of 6-Substituted Adenosine Analogues as Potent Inhibitors of Mycobacterium tuberculosis Adenosine Kinase, SDS of cas: 180698-19-5, the publication is Journal of Medicinal Chemistry (2019), 62(9), 4483-4499, database is CAplus and MEDLINE.

Mycobacterium tuberculosis adenosine kinase (MtbAdoK) is an essential enzyme of Mtb and forms part of the purine salvage pathway within mycobacteria. Evidence suggests that the purine salvage pathway might play a crucial role in Mtb survival and persistence during its latent phase of infection. In these studies, we adopted a structural approach to the discovery, structure-guided design, and synthesis of a series of adenosine analogs that displayed inhibition constants ranging from 5 to 120 nM against the enzyme. Two of these compounds exhibited low micromolar activity against Mtb with half maximal effective inhibitory concentrations of 1.7 and 4.0 μM. Our selectivity and preliminary pharmacokinetic studies showed that the compounds possess a higher degree of specificity against MtbAdoK when compared with the human counterpart and are well tolerated in rodents, resp. Finally, crystallog. studies showed the mol. basis of inhibition, potency, and selectivity and revealed the presence of a potentially therapeutically relevant cavity unique to the MtbAdoK homodimer.

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, SDS of cas: 180698-19-5.

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

Huang, Yiyun published the artcileSynthesis of potent and selective serotonin 5-HT_1B receptor ligands, Synthetic Route of 180698-19-5, the publication is Bioorganic & Medicinal Chemistry Letters (2005), 15(21), 4786-4789, database is CAplus and MEDLINE.

A series of serotonin 5-HT_1B ligands were synthesized and evaluated for their potency and selectivity against other 5-HT receptor subtypes. Many of these new compounds displayed high affinity and selectivity for the 5-HT_1B receptor and one compound was found to have the in vitro binding profile necessary for development as a PET radioligand.

Bioorganic & Medicinal Chemistry Letters 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, Synthetic Route of 180698-19-5.

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

Deka, Nabajyoti published the artcileSynthesis of N-(6-(4-(piperazin-1-yl)phenoxy)pyridin-3-yl)benzenesulfonamide derivatives for the treatment of metabolic syndrome, Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, the publication is International Journal of Medicinal Chemistry (2013), 201580/1-201580/11, 11 pp., database is CAplus and MEDLINE.

Metabolic syndrome is a widely prevalent multifactorial disorder associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. High plasma levels of insulin and glucose due to insulin resistance are a major component of the metabolic disorder. Thiazolidinediones (TZDs) are potent PPARγ ligands and used as insulin sensitizers in the treatment of type 2 diabetes mellitus. They are potent insulin-sensitizing agents but due to adverse effects like hepatotoxicity, a safer alternative of TZDs is highly demanded. The synthesis of N-(6-(4-(piperazin-1-yl)phenoxy)pyridin-3-yl)benzenesulfonamide derivatives I (R = 2,4-Cl₂C₆H₃, 2,5-(OCH₃)₂C₆H₃, 2-thienyl, etc.) an alternate remedy for insulin resistance is reported.

International 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, Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone.

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

Sasmal, Sanjita published the artcileDesign and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists, SDS of cas: 71260-16-7, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(9), 3157-3162, database is CAplus and MEDLINE.

Melanin concentrating hormone (MCH) is an important mediator of energy homeostasis and plays a role in metabolic and CNS disorders. The modeling-supported design, synthesis and multi-parameter optimization (biol. activity, solubility, metabolic stability, hERG) of novel quinazoline derivatives as MCHR1 antagonists are described. The in vivo proof of principle for weight loss with a lead compound from this series is exemplified. Clusters of refined hMCHR1 homol. models derived from the X-ray structure of the β2-adrenergic receptor, including extracellular loops, were developed and used to guide the design.

Bioorganic & Medicinal Chemistry Letters published new progress about 71260-16-7. 71260-16-7 belongs to piperazines, auxiliary class Piperazine, name is 2-Methyl-1-(piperazin-1-yl)propan-1-one, and the molecular formula is C8H16N2O, SDS of cas: 71260-16-7.

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