Category: piperazines

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

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

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

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

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

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

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

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

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

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