1094-91-3

Upstream product

• 98-59-9 p-toluenesulfonyl chloride 
• 3663-82-9 2-hydroxymethyl-2,3-dihydrobenzo[1,4]dioxin 
• 4739-94-0 ethyl 2,3-dihydro-1,4-benzodioxin-2-carboxylate 
• 3663-79-4 methyl 2,3-dihydrobenzo[b][1,4]dioxine-2-carboxylate 

Downstream Products

• 131728-89-7 N-(phenyl)-N-[1-(1,4-benzodioxan-2-yl(methyl))-4-methoxycarbonyl-4-piperidinyl]propanamide 
• 21867-81-2 1-benzyl-4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-piperazine 
• 148834-04-2 2-((4-formylphenoxy)methyl)-2,3-dihydrobenzo[1,4]dioxine 
• 18505-91-4 2-(2,3-Dihydro-1,4-benzodioxin-2-yl)acetonitrile 
• 306967-88-4 2-{[1-(2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidin-4-ylmethyl]aminomethyl}phenylamine 
• 306967-87-3 [1-(2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidin-4-ylmethyl]-2-nitrobenzylamine 
• 1026057-38-4 {2-[1-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-piperidin-4-yl]-ethyl}-(2-nitro-benzyl)-amine 
• 306968-22-9 N-{2-[1-(2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidin-4-yl]ethyl}-N'-phenylethane-1,2-diamine 

Relevant academic research and scientific papers

Development of novel LP1-based analogues with enhanced delta opioid receptor profile

Pain relief achieved by co-administration of drugs acting at different targets is more effective than that obtained with conventional MOR selective agonists usually associated to relevant side effects. It has been demonstrated that simultaneously targeting different opioid receptors is a more effective therapeutic strategy. Giving the promising role for DOR in pain management, novel LP1-based analogues with different N-substituents were designed and synthesized with the aim to improve DOR profile. For this purpose, we maintained the phenyl ring in the N-substituent of 6,7-benzomorphan scaffold linked to an ethyl spacer bearing a hydroxyl/methyl or methoxyl group at carbon 2 or including it in a 1,4-benzodioxane ring. LP1 analogues were tested by competition binding assays. Compounds 6 (KiMOR = 2.47 nM, KiDOR = 9.6 nM), 7 (KiMOR = 0.5 nM and KiDOR = 0.8 nM) and 9 (KiMOR = 1.08 nM, KiDOR = 6.6 nM) retained MOR affinity but displayed an improved DOR binding capacity as compared to LP1 (KiMOR = 0.83 nM, KiDOR = 29.1 nM). Moreover, GPI and MVD functional assays indicated that compounds 6 (IC50 = 49.2 and IC50 = 10.8 nM), 7 (IC50 = 9.9 and IC50 = 11.8 nM) and 9 (IC50 = 21.5 and IC50 = 4.4 nM) showed a MOR/DOR agonist profile, unlike LP1 that was a MOR agonist/DOR antagonist (IC50 = 1.9 and IC50 = 1240 nM). Measurements of their antinociceptive effect was evaluated by mice radiant tail flick test displaying for compounds 6, 7 and 9 ED50 values of 1.3, 1.0 and 0.9 mg/kg, i.p., respectively. Moreover, the antinociceptive effect of compound 9 was longer lasting with respect to LP1. In conclusion the N-substituent nature of compounds 6, 7 and 9 shifts the DOR profile of LP1 from antagonism to agonism.

Halogen bonding enhances activity in a series of dual 5-HT6/D2 ligands designed in a hybrid bioisostere generation/virtual screening protocol

A novel hybrid bioisostere generation/virtual screening method combined with narrowing of chemical space through similarity to compounds that are active at the second target was successfully applied for the development of structurally new dual 5-HT6/D2 receptor ligands. Consequently, a series of derivatives of the found hit 1d (N-[2-(dimethylamino)ethyl]-N-(2-phenylethyl)aniline) was synthesized. The most active 5-HT6/D2 ligands also showed affinity for 5-HT7R and 5-HT2AR. The para-chloroaniline derivative was identified as a potent dual 5-HT6/5-HT7 receptor antagonist (Ki = 24 nM and Kb = 30 nM, Ki = 4 nM and Kb = 1.4 nM, respectively). In the case of halogen-containing compounds, interesting structure-activity relationships were observed at 5-HT6, D2 and 5-HT7 receptors, and the ligand-receptor complexes were subsequently examined using a molecular modelling approach that combined quantum-polarized ligand docking (QPLD) and Molecular-Mechanics-Generalized-Born/Surface Area (MM/GBSA) free-energy calculation, which permitted the identification of putative halogen binding pockets.

Benzocarbazoles dioxa like derivative and its application

Provided are a benzodioxane compound as shown by the general formula (I), a pharmaceutical composition comprising same and the use thereof in treating psychotic and neuropathic diseases, particularly depression.

Synthesis and evaluation of novel 2,3-dihydrobenzo[b][1,4]dioxin- and indolealkylamine derivatives as potential antidepressants

A series of 2,3-dihydrobenzo[b][1,4]dioxin- and indolealkylamine derivatives were synthesized and the target compounds were evaluated for their binding affinities at the 5-HT1A receptor and serotonin transporter. Antidepressant-like activities of the compounds were screened using the tail suspension and forced swim tests in mice. Preliminary results indicated that the target compounds exhibited high binding affinities at the 5-HT1A receptor and serotonin transporter, and produced marked antidepressant-like effects. The best example from this study, compound 5, exhibited high binding affinities for the 5-HT1A receptor (Ki = 96 nM) and serotonin transporter (Ki = 9.8 nM). The intrinsic activity of compound 5 showed agonistic property to the 5-HT1A receptor and inhibition of the 5-HT transporter. Furthermore, compound 5 exhibited greater antidepressant efficacy than fluoxetine and showed acceptable pharmacokinetic properties. A series of 3-(2-(4-((2,3-dihydrobenzo[b][1,4]dioxin-3-yl)methyl) piperazin-1-yl)ethyl-1H-indole derivatives were synthesized and the target compounds were evaluated for their antidepressant activities in vitro and in vivo. The compounds described were also evaluated for dual 5-HTT and 5-HT 1A receptor activities.

Rapid synthesis, screening, and identification of xanthone- And xanthene-based fluorophores using click chemistry

A panel of new fluorophores with emission wavelengths from blue to yellow regions using the Cu(l)-catalyzed 1,3-dipolar cycloaddition reaction of alkyne-functionalized xanthones and xanthenes with various azides have been synthesized. Screening of the "cl

Synthesis and glycogen phosphorylase inhibitor activity of 2,3-dihydrobenzo[1,4]dioxin derivatives

Novel 5-benzyl and 5-benzylidene-thiazolidine-2,4-diones carrying 2,3-dihydrobenzo[1,4]dioxin pharmacophore were synthesized and their glycogen phosphorylase inhibitor activity was also studied.

Synthesis and structure-activity relationships of 1-aralkyl-4- benzylpiperidine and 1-aralkyl-4-benzylpiperazine derivatives as potent σ ligands

In the attempt to define more accurately structure-affinity relationships for σ1 and σ2 ligands, we synthesized and tested on σ subtype receptors a series of aralkyl derivatives of 4-benzylpiperidine, in which the effect of modificat

Catalytic regioselective sulfonylation of α-chelatable alcohols: Scope and mechanistic insight

This paper describes a convenient protocol for the regioselective sulfonylation of α-chelatable alcohols. Typically, the reaction of α-heterosubstituted alcohols with 1 equiv of p-TsCl and 1 equiv of Et3N in the presence of 2 mol % of Bu2SnO leads to rapid, regioselective, and exclusive monotosylation. The pKa of the amine was correlated to the reaction rate. A plausible mechanism for this reaction has been proposed on the basis of 119Sn NMR studies.

N-Hydroxyl derivatives of guanidine based drugs as enzymatic NO donors

Recent research suggests that NO may play a role in the physiological effects of some guanidine-containing drugs. In this report, three guanidine-containing drugs (guanadrel, guanoxan, and guanethidine) together with their N-hydroxyl derivatives were synthesized and their NO-releasing abilities catalyzed by nitric oxide synthases (NOSs) and horseradish peroxidase were evaluated. The guanidine containing compounds could not release NO in the presence of NOS or peroxidase. The corresponding N-hydroxyl compounds exhibited weak NO-releasing ability under the catalyzed of NOS and good NO-releasing ability under the oxidation by horseradish peroxidase in the presence of H2O2. These compounds also displayed vasodilatory activity. Elsevier Science Ltd. All rights reserved.

Selective sulfonylation of 1,2-diols and derivatives catalyzed by a recoverable fluorous tin oxide

Fluorous tin oxide (C6F13CH2CH2)2SnO is readily synthesized, exhibits spectra that are generally similar to dibutyltin oxide and appears to exist as an oligomer or polymer. The fluorous tin oxide can be used catalytically to effect the selective monotosylation of 1,2-diols with TsCl/Et3N, and it can be readily recovered and reused. (C) 2000 Published by Elsevier Science Ltd.