Month: November 2022

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

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

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

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

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

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

Dei, Silvia published the artcileDesign and synthesis of new potent N,N-bis(arylalkyl)piperazine derivatives as multidrug resistance (MDR) reversing agents, Computed Properties of 87179-40-6, the publication is European Journal of Medicinal Chemistry (2018), 7-20, database is CAplus and MEDLINE.

A series of 1,4-substituted arylalkyl piperazine derivatives I (Ar = 2-phenoxyethyl, 4,4-diphenylbutyl, 9-anthracenylmethyl, etc.; Ar¹ = cinnamyl, 4,4-bis(4-fluorophenyl)butyl, 4,4-bis(4-methoxyphenyl)butyl, etc.) were synthesized and studied with the aim to obtain potent P-gp-dependent multidrug-resistant (MDR) reversers. The new compounds were designed on the basis of the structures of previous arylamine ester derivatives endowed with high P-gp-dependent multidrug resistance reversing activity. All new compounds were active in the pirarubicin uptake assay on the doxorubicin-resistant erythroleukemia K562cells (K562/DOX). In particular, compounds bearing methoxy aromatic moieties showed fairly high reversal activities. The most potent compounds, I (Ar = (3,4,5-trimethoxyphenoxy)ethyl, 3,4,5-trimethoxycinnamyl, 3,4,5-trimethoxybenzyl; Ar¹ = 4,4-bis-(4-methoxyphenyl)butyl, 9-anthracenylmethyl) were further studied by evaluating their doxorubicin cytotoxicity enhancement (reversal fold, RF) and the inhibition of P-gp-mediated rhodamine-123 (Rhd 123) efflux on the K562/DOX cell line. The results of all pharmacol. assays indicated that the combination of a basic piperazine scaffold with arylalkyl residues allowed us to obtain very interesting P-gp modulating compounds Overall compound I (Ar = (3,4,5-trimethoxyphenyl)allyl; Ar¹ = 4,4-bis-(4-methoxyphenyl)butyl) appeared the most promising compound being a potent and long-lasting P-gp-dependent MDR modulator.

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

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

El Kihel, Laila published the artcileNew lithocholic and chenodeoxycholic piperazinylcarboxamides with antiproliferative and pro-apoptotic effects on human cancer cell lines, Category: piperazines, the publication is Bioorganic & Medicinal Chemistry (2008), 16(18), 8737-8744, database is CAplus and MEDLINE.

Six new synthetic bile acid derivatives were synthesized and tested in vitro against various human cancer cells (glioblastoma multiforme (GBM), multiple myeloma (KMS-11), and colonic carcinoma (HCT-116)) cell lines. The best activity was obtained with compound (I) on multiple myeloma cells (LD₅₀: 8.5±0.5 μM). This activity was associated with Mcl-1 and PARP-1 cleavage, inhibition of NFκB signaling, and DNA fragmentation, demonstrating an apoptotic cell death signaling pathway.

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

Bond, Michael J. published the artcileTargeted Degradation of Oncogenic KRAS^G12C by VHL-Recruiting PROTACs, Application In Synthesis of 2502156-03-6, the publication is ACS Central Science (2020), 6(8), 1367-1375, database is CAplus and MEDLINE.

KRAS is mutated in ~20% of human cancers and is one of the most sought-after targets for pharmacol. modulation, despite having historically been considered “undruggable.” The discovery of potent covalent inhibitors of the KRAS^G12C mutant in recent years has sparked a new wave of interest in small mols. targeting KRAS. While these inhibitors have shown promise in the clinic, we wanted to explore PROTAC-mediated degradation as a complementary strategy to modulate mutant KRAS. Herein, we report the development of LC-2(I), the first PROTAC capable of degrading endogenous KRAS^G12C. LC-2 covalently binds KRAS^G12C with a MRTX849 warhead and recruits the E3 ligase VHL, inducing rapid and sustained KRAS^G12C degradation leading to suppression of MAPK signaling in both homozygous and heterozygous KRAS^G12C cell lines. LC-2 demonstrates that PROTAC-mediated degradation is a viable option for attenuating oncogenic KRAS levels and downstream signaling in cancer cells. KRAS is one of the most sought-after targets for cancer therapy. Herein, we report the development of LC-2, the first PROTAC capable of inducing endogenous KRAS^G12C degradation by recruiting VHL.

ACS Central Science published new progress about 2502156-03-6. 2502156-03-6 belongs to piperazines, auxiliary class PROTACs,K-Ras (G12C)/PROTAC, name is (2S,4R)-1-((S)-2-(3-(3-((S)-2-(((7-(8-Chloronaphthalen-1-yl)-4-((S)-3-(cyanomethyl)-4-(2-fluoroacryloyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)oxy)methyl)pyrrolidin-1-yl)propoxy)propanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide, and the molecular formula is C59H71ClFN11O7S, Application In Synthesis of 2502156-03-6.

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

Ding, Huaiwei published the artcileSynthesis and cytotoxic activity of some novel N-pyridinyl-2-(6-phenylimidazo[2,1-b]thiazol-3-yl)acetamide derivatives, HPLC of Formula: 55403-35-5, the publication is Molecules (2012), 4703-4716, database is CAplus and MEDLINE.

Novel compounds bearing imidazo[2,1-b]thiazole scaffolds were designed and synthesized based on the optimization of the virtual screening hit compound N-(6-morpholinopyridin-3-yl)-2-(6-phenylimidazo[2,1-b]thiazol-3-yl)acetamide (I) and were tested for their cytotoxicity against human cancer cell lines, including HepG2 and MDA-MB-231. 2-{6-(4-Chlorophenyl)imidazo[2,1-b]thiazol-3-yl}-N-{6-[4-(4-methoxybenzyl)piperazin-1-yl]pyridin-3-yl}acetamide, with slightly higher inhibition on VEGFR2 than I (5.72 and 3.76% inhibitory rate at 20 μM, resp.), was a potential inhibitor against MDA-MB-231 (IC₅₀ = 1.4 μM) compared with sorafenib (IC₅₀ = 5.2 μM), and showed more selectivity against MDA-MB-231 than HepG2 cell line (IC₅₀ = 22.6 μM).

Molecules 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, HPLC of Formula: 55403-35-5.

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