86255-43-8

Upstream product

• 75-52-5 nitromethane 
• 7311-34-4 3,5-dimethoxybenzaldehdye 

Downstream Products

• 56723-83-2 2-(3,5-dimethoxyphenyl)nitroethane 
• 81289-19-2 2-(3,5-Dimethoxy-phenyl)-3-nitro-2H-chromene 
• 3213-28-3 3,5-dimethoxyphenethylamine 
• 86712-41-6 3,5-dimethoxy-2,β-dinitrostyrene 
• 853133-56-9 1-benzyl-5,7-dimethoxyindole 
• 81289-39-6 2-[3-(3,5-Dimethoxy-phenyl)-2-nitro-propyl]-phenol 
• 56723-85-4 3-(3,5-Dimethoxy-phenyl)-2-nitro-propan-1-ol 
• 29866-11-3 3,5-dihydroxyphenylethylamine 
• 912644-21-4 3,5-bis(3,5-dimethoxyphenyl)-1H-pyrrole-2-methyl carboxylate 
• 912644-36-1 3,5-bis(3,5-dimethoxyphenyl)-4-nitro-1H-pyrrole-2methyl carboxylate 
• 1215288-69-9 4-bromo-3,5-dimethoxy-β-nitrostyrene 
• 1215288-68-8 1-acetylamino-2,2-dibromo-1-(3,5-dimethoxyphenyl)-2-nitroethane 
• 1215288-70-2 1-acetylamino-2,2-dibromo-1-(4-bromo-3,5-dimethoxyphenyl)-2-nitroethane 

Relevant academic research and scientific papers

Synthesis and Functional Characterization of 2-(2,5-Dimethoxyphenyl)-N-(2-fluorobenzyl)ethanamine (25H-NBF) Positional Isomers

Serotonergic psychedelics, substances exerting their pharmacological action through activation of the serotonin 2A receptor (5-HT2AR), have continuously comprised a substantial fraction of the over 1000 reported New Psychoactive Substances (NPS) so far. Within this category, N-benzyl derived phenethylamines, such as NBOMes and NBFs, have shown to be of particular relevance. As these substances remain incompletely characterized, this study aimed at synthesizing positional isomers of 25H-NBF, with two methoxy groups placed on different positions of the phenyl group of the phenethylamine moiety. These isomers were then functionally characterized in an in vitro bioassay monitoring the recruitment of β-Arrestin 2 to the 5-HT2AR through luminescent readout via the NanoBiT technology. The obtained results provide insight into the optimal substitution pattern of the phenyl group of the phenethylamine moiety of N-benzyl derived substances, a feature so far mostly explored in the phenethylamines underived at the N-position. In the employed bioassay, the most potent substances were 24H-NBF (EC50 value of 158 nM), 26H-NBF (397 nM), and 25H-NBF (448 nM), with 23H-NBF, 35H-NBF, and 34H-NBF yielding μM EC50 values. A similar ranking was obtained for the compounds' efficacy: Taking as a reference LSD (lysergic acid diethylamide), 24H-, 26H-, and 25H-NBF had an efficacy of 106-107%, followed by 23H-NBF (96.1%), 34H-NBF (75.2%), and 35H-NBF (58.9%). The stronger activity of 24H-, 25H-, and 26H-NBF emphasizes the important role of the methoxy group at position 2 of the phenethylamine moiety for the in vitro functionality of NBF substances.

Synthesis of Functionalized Indolines and Dihydrobenzofurans by Iron and Copper Catalyzed Aryl C-N and C-O Bond Formation

A simple and effective one-pot, two-step intramolecular aryl C-N and C-O bond forming process for the preparation of a wide range of benzo-fused heterocyclic scaffolds using iron and copper catalysis is described. Activated aryl rings were subjected to a highly regioselective, iron(III) triflimide-catalyzed iodination, followed by a copper(I)-catalyzed intramolecular N-or O-arylation step leading to indolines, dihydrobenzofurans, and six-membered analogues. The general applicability and functional group tolerance of this method were exemplified by the total synthesis of the neolignan natural product, (+)-obtusafuran. DFT calculations using Fukui functions were also performed, providing a molecular orbital rationale for the highly regioselective arene iodination process.

Direct dihalo-alkoxylation of nitroalkenes leading to β,β-dihalo-β-nitroethyl alkyl ethers

A highly efficient one-pot synthesis of β,β-dihalo-β-nitroethyl alkyl ethers is achieved by the treatment of nitroalkenes with alcohols and N-halosuccinimides in the presence of sodium hydride. The notable advantages of this protocol are that it involves simple experimental manipulations and tolerates a wide range of functional groups. Further transformations of the obtained ethers, such as allylation and conversion to β,β-dihalogenated vinyl ethers, are also investigated.

Direct aziridination of nitroalkenes affording N-alkyl-C-nitroaziridines and the subsequent Lewis acid mediated isomerization to β-nitroenamines

A mild and highly diastereoselective one-pot synthesis of trans-N-alkyl-C-nitroaziridines was achieved by treatment of nitroalkenes with aliphatic amines and N-chlorosuccinimide. Treatment of the obtained aziridines with a Lewis acid resulted in a facile ring opening reaction, accompanied by rearrangement and isomerization into functionalized (Z)-β-nitroenamines.

Synthesis of 3-Benzazepines by Metal-Free Oxidative C–H Bond Functionalization–Ring Expansion Tandem Reaction

A metal-free synthesis of biologically important benzazepines is achieved through a single synthetic operation involving an oxidative C–H bond functionalization and ring expansion with diazomethanes as key reagent. This represents a new, strong methodology for the straightforward construction of the seven-ring N-heterocyclic structures under mild conditions using a 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) oxoammonium salt as oxidant. Moderate to good yields are achieved from simple, readily available tetrahydroisoquinolines, and this methodology has been further successfully applied for the synthesis of the 3-benzazepine drug Lorcaserin. A possible mechanistic pathway for the ring expansion step, comprising the extrusion of nitrogen in a concerted asynchronic process, is proposed based on both mechanistic proof and density function theory (DFT) calculations. (Figure presented.).

Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability

Cannabidiol is the nonpsychoactive natural component of C. sativa that has been shown to be neuroprotective in multiple animal models. Our interest is to advance a therapeutic candidate for the orphan indication hepatic encephalopathy (HE). HE is a serious neurological disorder that occurs in patients with cirrhosis or liver failure. Although cannabidiol is effective in models of HE, it has limitations in terms of safety and oral bioavailability. Herein, we describe a series of side chain modified resorcinols that were designed for greater hydrophilicity and "drug likeness", while varying hydrogen bond donors, acceptors, architecture, basicity, neutrality, acidity, and polar surface area within the pendent group. Our primary screen evaluated the ability of the test agents to prevent damage to hippocampal neurons induced by ammonium acetate and ethanol at clinically relevant concentrations. Notably, KLS-13019 was 50-fold more potent and >400-fold safer than cannabidiol and exhibited an in vitro profile consistent with improved oral bioavailability.

Convenient syntheses of 3-aryl-3,4-dihydroisocoumarins

A convenient method for the synthesis of naturally occurring 3,4-dihydroisocoumarins by judicious use of Friedel-Craft acylation, regioselective formylation and oxidative cyclisation reactions is described. O-methylated analogues of montroumarin and thunb

Synthesis, biological screening and ADME prediction of benzylindole derivatives as novel anti-HIV-1, anti-fungal and anti-bacterial agents

Present study is focused on design, synthesis, and biological evaluation of substituted benzylindole derivatives as anti-HIV, anti-fungal, and anti-bacterial agents. Out of the reported compounds, compound B1 and B2 showed potent Anti-HIV activity, wherea

Design, synthesis, and pharmacological evaluation of novel tetrahydroprotoberberine derivatives: Selective inhibitors of dopamine D 1 receptor

A series of new tetrahydroprotoberberine (THPB) derivatives were designed, synthesized, and tested for their binding affinity towards dopamine (D 1 and D2) and serotonin (5-HT1A and 5-HT 2A) receptors. Many of the THPB compounds exhibited high binding affinity and activity at the dopamine D1 receptor, as well as high selectivity for the D1 receptor over the D2, 5-HT 1A, and 5-HT2A receptors. Among these, compound 19c exhibited a promising D1 receptor binding affinity (Ki = 2.53 nM) and remarkable selectivity versus D2R (inhibition = 81.87%), 5-HT1AR (inhibition = 61.70%), and 5-HT2AR (inhibition = 24.96%). Compared with l-(S)-stepholidine (l-SPD) (D1 Ki = 6.23 nM, D2 Ki = 56.17 nM), compound 19c showed better binding affinity for the D1 receptor (2.5-fold higher) and excellent D2/D1 selectivity. Functional assays found compounds 18j, 18k, and 19c are pure D1 receptor antagonists. These results indicate that removing the C10 hydroxy group and introducing a methoxy group at C11 of the pharmacophore of l-SPD can reverse the function of THPB compounds at the D1 receptor. These results are in accord with molecular docking studies.

HIV-1 integrase strand-transfer inhibitors: Design, synthesis and molecular modeling investigation

This study is focused on a new series of benzylindole derivatives with various substituents at the benzene-fused ring, suggested by our 3D pharmacophore model developed for HIV-1 integrase inhibitors (INIs). All synthesized compounds proved to be active in the nanomolar range (6-35 nM) on the strand-transfer step (ST). In particular, derivative 4-[1-(4-fluorobenzyl)- 5,7-dimethoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (8e), presenting the highest best-fit value on pharmacophore model, showed a potency comparable to that of clinical INSTIs GS 9137 (1) and MK-0518 (2). The binding mode of our molecules has been investigated using the recently published crystal structure of the complex of full-length integrase from the prototype foamy virus in complex with its cognate DNA (PFV-IN/DNA). The results highlighted the ability of derivative 8e to assume the same binding mode of MK-0518 and GS 9137.