Category: 5961-59-1

Lu, Chunlei published the artcileScalable direct N-methylation of drug-like amines using 12CO2/13CO2 by simple inorganic base catalysis, Safety of 4-Methoxy-N-methylaniline, the main research area is methyl amine preparation; amine carbon dioxide methylation tripotassium phosphate catalyst.

A general protocol for scalable direct N-methylation of wide-scope drug-like amines such as duloxetine, sertraline, tetrahydropapaverine, rasagiline, etc. using CO2 and polymethylhydrosiloxane-a nontoxic, aerobically-stable hydrosilane considered as an industrial waste-via simple inorganic base catalysis has been developed. A rare application of the Sabatier principle in organic chem. led to the discovery of cheap, nontoxic K3PO4 as an efficient catalyst. Preparations of a wide-scope drug-like amines with carbon-isotope label, e.g., I were also successfully achieved, enabling direct use of CO2 in studies of drug absorption, distribution, metabolism and excretion.

Science Bulletin published new progress about Methylation. 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Safety of 4-Methoxy-N-methylaniline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Alqahtani, Mona A. published the artcileBio fabrication of silver nanoparticles with antibacterial and cytotoxic abilities using lichens, Related Products of isoquinoline, the main research area is silver nanoparticle antibacterial cytotoxic lichen biofabrication.

Recently, increase bacterial resistance to antimicrobial compounds issue constitutes a real threat to human health. One of the useful materials for bacterial control is Silver nanoparticles (AgNPs). Researchers tend to use biogenic agents to synthesize stable and safe AgNPs. The principal aim of this study was to investigate the ability of lichen in AgNPs formation and to find out their suppression ability to MDR bacteria as well as their cytotoxic activity. In the current study, lichens (Xanthoria parietina, Flavopunctelia flaventior) were collected from the south of the Kingdom of Saudi Arabia. Lichens methanolic extracts were used for conversion of Ag ions to AgNPs. Prepared biogenic AgNPs were characterized by UV-Visible (UV-Vis) Spectroscopy, Transmission electron microscopy (TEM), Dynamic Light Scattering (DLS) and Zeta potential and Energy-Dispersive X-ray Spectroscopy (EDS). Lichens Secondary metabolites were determined by Fourier-Transform IR Spectroscopy (FTIR) and Gas Chromatog.-Mass Spectrometry (GC-MS). The antibacterial activity and synergistic effect of AgNPs were evaluated against pathogenic bacteria, including gram-pos.; Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococcus (VRE), and gram-neg.; (Pseudomonas aeruginosa, Escherichia coli) as well as the reference strains (ATCC) using the agar disk diffusion method. Cytotoxic effect of biogenic AgNPs was tested against HCT 116 (Human Colorectal Cancer cell), MDA-MB-231 (Breast cancer cell), and FaDu (Pharynx cancer cell) by MTT test. TEM imaging showed well-dispersed spherical particles of 1-40 nm size as well as zeta size showed 69-145 nm. Furthermore, FTIR and GC-MS identified various lichen chem. mols. On the other hand, the highest antibacterial activity of AgNPs was noticed against P. aeruginosa, followed by MRSA, VRE, and E. coli. AgNPs influence on gram-neg. bacteria was greater than that on gram-pos. bacteria and their synergistic effect with some antibiotics was noted against examined microbes. Moreover, higher cytotoxicity for biogenic AgNPs against FaDu and HCT 116 cell line in relation to MDA-MB-231 was noted. Given the current findings, the biogenic AgNPs mediated by lichens had pos. antibacterial, synergistic and cytotoxic powers. Therefore, they might be considered as a promising candidate to combat the multi-drug resistance organisms and some cancer cells.

Scientific Reports published new progress about Adenocarcinoma. 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Related Products of isoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Sun, Lin published the artcileDesign, Synthesis, and Mechanism Study of Benzenesulfonamide-Containing Phenylalanine Derivatives as Novel HIV-1 Capsid Inhibitors with Improved Antiviral Activities, Product Details of C8H11NO, the main research area is amino acid benzenesulfonamide phenylalanine antiviral structure activity HIV1 pharmacokinetic; anti AIDS agent CA protein inhibitor MD simulation virion; mol docking hydrogen bond benzenesulfonamide phenylalanine metabolic stability; peptidomimetic peptide coupling drug design toxicity.

HIV-1 CA protein has gained remarkable attention as a promising therapeutic target for the development of new antivirals, due to its pivotal roles in HIV-1 replication (structural and regulatory). Herein, we report the design and synthesis of three series of benzenesulfonamide-containing phenylalanine derivatives obtained by further structural modifications of PF-74 to aid in the discovery of more potent and drug-like HIV-1 CA inhibitors. Structure-activity relationship studies of these compounds led to the identification of new phenylalanine derivatives with a piperazinone moiety, represented by compound (I), which exhibited anti-HIV-1NL4-3 activity 5.78-fold better than PF-74. Interestingly, I also showed anti-HIV-2ROD activity (EC50 = 31 nΜ), with almost 120 times increased potency over PF-74. However, due to the higher significance of HIV-1 as compared to HIV-2 for the human population, this manuscript focused on the mechanism of action of our compounds in the context of HIV-1. SPR studies on representative compounds confirmed CA as the binding target. The action stage determination assay demonstrated that these inhibitors exhibited antiviral activities with a dual-stage inhibition profile. The early-stage inhibitory activity of compound I was 6.25 times more potent as compared to PF-74, but appears to work via accelerating capsid core assembly rather than stabilization. However, the mechanism by which they exert their antiviral activity in the late-stage appears to be the same as PF-74 with less infectious HIV-1 virions are produced in their presence as judged p24 content studies. MD simulations provided the key rationale for the promising antiviral potency of I. Addnl., I exhibited modest increase in HLM and human plasma metabolic stabilities as compared to PF-74, as well as moderately improved pharmacokinetic profile, favorable oral bioavailability, and no acute toxicity. These studies provide insights and serves as a starting point for subsequent medicinal chem. efforts in optimizing these promising HIV inhibitors.

Journal of Medicinal Chemistry published new progress about AIDS (disease). 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Product Details of C8H11NO.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Wang, Lei published the artcileNovel HIV-1 capsid-targeting small molecules of the PF74 binding site, Related Products of isoquinoline, the main research area is HIV1 capsid targeting antiviral PF74 binding site; Capsid-targeting antivirals; HIV-1; Metabolic stability; PF74.

The PF74 (I) binding site in HIV-1 capsid protein (CA) is a compelling antiviral drug target. Although PF74 confers mechanistically distinct antiviral phenotypes by competing against host factors for CA binding, it suffers from prohibitively low metabolic stability. Therefore, there has been increasing interest in designing novel sub-chemotypes of PF74 with similar binding mode and improved metabolic stability. We report herein our efforts to explore the inter-domain interacting indole moiety for designing novel CA-targeting small mols. Our design includes simple substitution on the indole ring, and more importantly, novel sub-chemotypes with the indole moiety replaced with a few less electron-rich rings. All 56 novel analogs were synthesized and evaluated for antiviral activity, cytotoxicity, and impact on CA hexamer stability. Selected analogs were tested for metabolic stability in liver microsomes. Mol. modeling was performed to verify compound binding to the PF74 site. In the end, 5-hydroxyindole analogs (8,9 and 12, II – IV, resp.) showed improved potency (up to 20-fold) over PF74. Of the novel sub-chemotypes, α- and β-naphthyl analogs (27 and 33, V and VI, resp.) exhibited sub micromolar antiviral potencies comparable to that of PF74. Interestingly, although only moderately inhibiting HIV-1 (single-digit micromolar EC50s), analogs of the 2-indolone sub-chemotype consistently lowered the m.p. (Tm) of CA hexamers, some with improved metabolic stability over PF74.

European Journal of Medicinal Chemistry published new progress about AIDS (disease). 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Related Products of isoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Li, Gen published the artcileP(III)/P(V)-Catalyzed Methylamination of Arylboronic Acids and Esters: Reductive C-N Coupling with Nitromethane as a Methylamine Surrogate, Related Products of isoquinoline, the main research area is arylation nitromethane arylboronic acid organophosphorus catalyzed reductive coupling.

The direct reductive N-arylation of nitromethane by organophosphorus-catalyzed reductive C-N coupling with arylboronic acid derivatives is reported. This method operates by the action of a small ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide) together with a mild terminal reductant hydrosilane to drive the selective installation of the methylamino group to (hetero)aromatic boronic acids and esters. This method also provides for a unified synthetic approach to isotopically labeled N-methylanilines from various stable isotopologues of nitromethane (i.e., CD3NO2, CH315NO2, and 13CH3NO2), revealing this easy-to-handle compound as a versatile precursor for the direct installation of the methylamino group.

Journal of the American Chemical Society published new progress about Amination (Me). 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Related Products of isoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Zheng, Cameron H. M. published the artcileThe Catalytic Synthesis of N-Aryl Indoles Featuring an Alternative Disconnection. Hydroaminoalkylation for a Telescoped Reaction Sequence, Product Details of C8H11NO, the main research area is aryl indole preparation; chlorostyrene methylaniline hydroaminoalkylation tantalumureate catalyst.

A tricatalytic telescoped synthesis toward C3-methyl-N-aryl indolines I (R = cyclohexyl, Ph, 3,4-dimethoxyphenyl, 2-phenylethyl, etc.) and indoles II products is reported. An in situ generated tantalum(V) ureate catalyst is used for the hydroaminoalkylation of o-chlorostyrene with N-Me aniline RNHCH3 to first make a Csp3-Csp3 bond. Subsequent nickel-catalyzed C-N coupling forms N-aryl indolines I, and if desired, subsequent oxidation to N-aryl indoles II can be achieved using catalytic [Cu(MeCN)4]BF4 and tert-butylperoxy-2-ethylhexyl carbonate as the terminal oxidant. This strategy highlights an alternative C-C bond disconnection for the synthesis of indoles II, which is enabled by the atom-economic hydroaminoalkylation reaction. The method was streamlined using a three-step, two-pot approach to afford up to 73% overall isolated yield of variously substituted C3-methyl-N-aryl indoles II.

Organic Letters published new progress about Aminoalkylation. 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Product Details of C8H11NO.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Jiang, Xiangyi published the artcileDiscovery of novel 1,4-disubstituted 1,2,3-triazole phenylalanine derivatives as HIV-1 capsid inhibitors, SDS of cas: 5961-59-1, the main research area is structure activity HIV capsid inhibitor triazole phenylalanine; triazole phenylalanine derivative preparation HIV capsid inhibitor; CuAAC; HIV-1; HIV-1 capsid protein; Molecular dynamics simulation; Phenylalanine derivatives; SAR; Surface plasmon resonance.

The HIV-1 capsid (CA) protein plays crucial roles in both early and late stages of the viral life cycle, which has intrigued researchers to develop anti-HIV drugs that target it. Accordingly, in this research, we report the design, synthesis and biol. evaluation of a series of novel phenylalanine derivatives as HIV-1 CA protein inhibitors using the Cu(I)-catalyzed azide and alkyne 1,3-dipolar cycloaddition (CuAAC) reaction. Among this series of inhibitors, compound I displayed a remarkable anti-HIV activity (EC50 = 2.13μM, CC50 > 35.49μM). Furthermore, surface plasmon resonance (SPR) binding assays showed that compounds I and PF-74 (II, lead compound) have similar affinities to the HIV-1 CA monomer. Further investigation showed that the weak permeability and water solubility of representative compounds were probably the important factors that restricted their cell-based activity. Preliminary structure-activity relationships (SARs) were inferred based on the activities of these compounds and their known structure. The most promising new compound was studied with mol. dynamics simulation (MD) to determine the preferred interactions with the drug target. Finally, the activities of members of this series of inhibitors were deeply inspected to find the potential reasons for their anti-HIV-1 activity from various perspectives. This highlights the important factors required to design compounds with improved potency.

RSC Advances published new progress about Anti-HIV agents. 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, SDS of cas: 5961-59-1.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Wang, Lei published the artcileChemical profiling of HIV-1 capsid-targeting antiviral PF74, Application of 4-Methoxy-N-methylaniline, the main research area is indole peptidomimetic synthesis antiviral HIV cytotoxicity CA hexamer stability; Capsid-targeting antivirals; HIV-1; PF74.

The capsid protein (CA) of HIV-1 plays essential roles in multiple steps of the viral replication cycle by assembling into functional capsid core, controlling the kinetics of uncoating and nuclear entry, and interacting with various host factors. Targeting CA represents an attractive yet underexplored antiviral approach. Of all known CA-targeting small mol. chemotypes, the peptidomimetic PF74, I, is particularly interesting because it binds to the same pocket used by a few important host factors, resulting in highly desirable antiviral phenotypes. However, further development of I entails understanding its pharmacophore and mitigating its poor metabolic stability. We report herein the design, synthesis, and evaluation of a large number of I analogs aiming to provide a comprehensive chem. profiling of I and advance the understanding on its detailed binding mechanism and pharmacophore. The analogs, containing structural variations mainly in the aniline domain and/or the indole domain, were assayed for their effect on stability of CA hexamers, antiviral activity, and cytotoxicity. Selected analogs were also tested for metabolic stability in liver microsomes, alone or in the presence of a CYP3A inhibitor. Collectively, our studies identified important pharmacophore elements and revealed addnl. binding features of I, which could aid in future design of improved ligands to better probe the mol. basis of CA-host factor interactions, design strategies to disrupt them, and ultimately identify viable CA-targeting antiviral leads.

European Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Application of 4-Methoxy-N-methylaniline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Mayoka, Godfrey published the artcileStructure-Activity Relationship and in Vitro Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) Studies of N-aryl 3-Trifluoromethyl Pyrido[1,2-a]benzimidazoles That Are Efficacious in a Mouse Model of Schistosomiasis, Computed Properties of 5961-59-1, the main research area is Schistosoma mansoni newly transformed schistosomula antschistosomal lead; Schistosoma mansoni; antischistosomal lead; newly transformed schistosomula; pyrido[1,2-a]benzimidazole.

We have previously reported on the antischistosomal activity of pyrido[1,2-a]benzimidazole (PBI) derivatives As a follow-up, we designed and prosecuted further structure-activity relationship (SAR) studies that incorporate N-aryl substitutions on the PBI scaffold. Investigations into the in vitro antischistosomal activity against newly transformed schistosomula (NTS) and adult worms revealed several leads with promising potency. Active compounds with a good cytotoxicity profile were tested in vivo whereby 6 and 44 induced noteworthy reduction (62-69%) in the worm load in the Schistosoma mansoni mouse model. Pharmacokinetic anal. on 44 (8-Dichloro-1-((2-fluorobenzyl)amino)-3(trifluoromethyl)benzo[4,5]imidazo[1,2-a]pyridine-4-carbonitrile) pointed to slow absorption, low volume of distribution, and low plasma clearance indicating the potential of these compounds to achieve a long duration of action. Overall, our work demonstrates that PBI chemotype is a promising scaffold in the discovery of new antischistosomal leads.

ACS Infectious Diseases published new progress about Pharmacokinetics. 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Computed Properties of 5961-59-1.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Zima, Vaclav published the artcileInvestigation of flexibility of neuraminidase 150-loop using tamiflu derivatives in influenza A viruses H1N1 and H5N1, COA of Formula: C8H11NO, the main research area is influenza A virus H1N1 H5N1 neuraminidase 150 loop antiviral; tamiflu oseltamivir crystal structure; Click chemistry; Crystal structure; Influenza neuraminidase; Oseltamivir.

This study focuses on design, synthesis and in vitro evaluation of inhibitory potency of two series of sialylmimetic that target an exosite (“”150-cavity””) adjacent to the active site of influenza neuraminidases from A/California/07/2009 (H1N1) pandemic strain and A/chicken/Nakorn-Patom/Thailand/CU-K2-2004 (H5N1). The structure-activity anal. as well as 3-D structure of the complex of parental compound with the pandemic neuraminidase p09N1 revealed high flexibility of the 150-cavity towards various modification of the neuraminidase inhibitors. Furthermore, our comparison of two methods for inhibition constant determination performed at slightly different pH values suggest that the exptl. conditions of the measurement could dramatically influence the outcome of the anal. in the compound-dependent manner. Therefore, previously reported Ki values determined at non-physiol. pH should be carefully scrutinized.

Bioorganic & Medicinal Chemistry published new progress about Antiviral agents. 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, COA of Formula: C8H11NO.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem