5466-91-1

Usage

InChI:InChI=1/C21H21N5O3/c1-15-19(21(28)26(24-15)16-7-3-2-4-8-16)23-22-18-10-6-5-9-17(18)20(27)25-11-13-29-14-12-25/h2-10,22H,11-14H2,1H3/b23-19-

Upstream product

• 100-01-6 4-nitro-aniline 
• 603-33-8 triphenylbismuthane 
• 98-80-6 phenylboronic acid 
• 98-09-9 benzenesulfonyl chloride 
• 98-10-2 benzenesulfonamide 
• 106-40-1 4-bromo-aniline 
• 106-50-3 1,4-phenylenediamine 
• 122-80-5 N-acetyl-p-phenylenediamine 
• 142-04-1 aniline hydrochloride 
• 36071-24-6 4-benzenesulfonylamino-benzenediazonium-betaine 
• 27022-75-9 4'-acetamidobenzenesulfonanilide 
• 1829-81-8 N-(4-nitrophenyl)benzenesulfonamide 

Downstream Products

• 873993-26-1 N-(4-bromoimino-cyclohexa-2,5-dienylidene)-benzenesulfonamide 
• 6658-72-6 4-benzenesulfonylamino-benzenediazonium; chloride 
• 5467-02-7 1-benzenesulfonylamino-4-pivaloylamino-benzene 
• 110194-21-3 1-benzenesulfonylamino-4-(3-oxo-3-phenyl-propionylamino)-benzene 
• 97376-69-7 benzo[b][1,10]phenanthrolin-7(12H)-one 
• 86785-39-9 4'-(bromoacetamido)benzenesulfonanilide 
• 134284-39-2 N¹-phenylsulfonyl-N⁴-(2-nitrophenylsulfonyl)-1,4-benzoquinone diimine 
• 134284-42-7 N-(4-Benzenesulfonylamino-3-chloro-phenyl)-2-nitro-benzenesulfonamide 
• 132904-25-7 N-[4-(Benzo[b][1,8]phenanthrolin-7-ylamino)-phenyl]-benzenesulfonamide 
• 86785-43-5 2'-chloro-4'-(bromoacetamido)benzenesulfonanilide 
• 86785-32-2 2-chloro-N¹-(phenylsulfonyl)-N⁴-(bromoacetyl)benzoquinone diimine 

Relevant academic research and scientific papers

Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds

Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.

N-(4-acetamidophenyl)-5-acetylfuran-2-carboxamide as a novel orally available diuretic that targets urea transporters with improved PD and PK properties

Urea transporters (UTs) have been identified as new targets for diuretics. Functional deletion of UTs led to urea-selective urinary concentrating defects with relative salt sparing. In our previous study, a UT inhibitor with a diarylamide scaffold, which is denoted as 11a, was demonstrated as the first orally available UT inhibitor. However, the oral bioavailability of 11a was only 4.38%, which obstructed its clinical application. In this work, by replacing the nitro group of 11a with an acetyl group, 25a was obtained. Compared with 11a, 25a showed a 10 times stronger inhibitory effect on UT-B (0.14 μM vs. 1.41 μM in rats, and 0.48 μM vs. 5.82 μM in mice) and a much higher inhibition rate on UT-A1. Moreover, the metabolic stability both in vitro and in vivo and the drug-like properties (permeability and solubility) of 25a were obviously improved compared with those of 11a. Moreover, the bioavailability of 25a was 15.18%, which was 3 times higher than that of 11a, thereby resulting in significant enhancement of the diuretic activities in rats and mice. 25a showed excellent potential for development as a promising clinical diuretic candidate for targeting UTs to treat diseases that require long-term usage of diuretics, such as hyponatremia.

Sequential C-S and S-N Coupling Approach to Sulfonamides

A one-pot three-component reaction involving nitroarenes, (hetero)arylboronic acids, and potassium pyrosulfite leading to sulfonamides was described. A broad range of sulfonamides bearing different reactive functional groups were obtained in good to excellent yields through sequential C-S and S-N coupling that does not require metal catalysts.

Synthesis and evaluation of 3-(4-(phenoxymethyl)phenyl)propanoic acid and N-phenylbenzenesulfonamide derivatives as FFA4 agonists

Free fatty acid receptor 4 (FFA4) has been recognized as an attractive target in metabolic diseases. To find potent and selective FFA4 agonist, 28 compounds of 3-(4-(phenoxymethyl)phenyl)propanoic acid and N-phenylbenzenesulfonamide derivatives were designed and synthesized, featuring O[sbnd]C and SO2-N linkage. For the O[sbnd]C linkage compounds, 1g showed the most potent FFA4 agonistic activity with a pEC50 of 5.81 ± 0.04 and exhibited at least 64-fold selectivity against FFA1. For SO2-N linkage agonists, 2m had a pEC50 of 5.66 ± 0.04 and displayed>46-fold selectivity against FFA1. Among these two series of compounds, 1g was the most potent agonist at FFA4 and the best selectivity against FFA1, demonstrated by docking simulation. Moreover, 1g showed receptor selectivity on other seven GPCRs. In anti-diabetic evaluation, 1g dose-dependently reduced blood glucose, which was better than a clinical phase III drug TAK875. This study provides guidance for FFA4 ligand design and drug optimization.

Method for coupling nitroaromatic compound and boric acid compound to synthesize sulfonamide compound

The invention belongs to the field of organic synthesis, and specifically discloses a method for coupling a nitroaromatic compound and a boric acid compound to synthesize a sulfonamide compound. The method for coupling the nitroaromatic compound and the boric acid compound to synthesize the sulfonamide compound comprises the steps that in an organic solvent, pyrosulfite is used as a source of SO2,and heating is carried out for a coupling reaction, and then after the post-treatment, the sulfonamide compound is obtained. The method for coupling the nitroaromatic compound and the boric acid compound to synthesize the sulfonamide compound is simple in operation, does not require nitrogen protection, and can be carried out under air. The nitroaromatic compound and the boric acid compound are abundant in source, relatively low in price, high in reaction yield, wide in applicability of a substrate and free in metal residual. The method for coupling the nitroaromatic compound and the boric acid compound to synthesize the sulfonamide compound can be used for synthesizing a series of sulfonamide compounds, and the synthesized compounds have wide application value in the fields of pesticidesand medicines.

Probing 2H-Indazoles as Templates for SGK1, Tie2, and SRC Kinase Inhibitors

The broader and systematic application of a novel scaffold is often hampered by the unavailability of a short and reliable synthetic access. We investigated a new strategy for the design and synthesis of an array of N2-substituted aza-2H-indazole derivatives as potential kinase inhibitors. Guided by a rational ligand alignment approach to qualify the so-far underrepresented aza-2H-indazole scaffold, indazoles were connected at the N2 position with a phenyl spacer and an arylsulfonamide or amide linkage. Initial profiling against a panel of 30 kinases confirmed the in silico predicted selectivity bias. A synthesized focused library of 52 different aza-2H-indazole derivatives showed good initial selective inhibition against SGK1, Tie2, and SRC kinases, with the best representatives having IC50 values in the range of 500 nm. In a comparative computational study, these data were analyzed and rationalized in light of docking studies.

Multicomponent synthesis of sulfonamides from triarylbismuthines, nitro compounds and sodium metabisulfite in deep eutectic solvents

A sustainable synthesis of sulfonamides using a copper-catalysed process starting from triarylbismuthines, Na2S2O5 and nitro compounds in a Deep Eutectic Solvent (DES) as a reaction medium is described. Thus, triarylbismuthines are used as reagents for the incorporation of SO2 into organic motifs. The bismuth salts formed as by-products can be easily removed from the crude reaction mixture by precipitation with water, while the use of volatile organic compounds (VOCs) as solvents can be avoided in the entire process. The eutectic mixture employed as the solvent is fully characterised, with the preliminary results proving its low toxicity. The designed DES also allows for a novel multicomponent reaction which saves time and reduces purification steps, energy and cost.

SMALL MOLECULE ACTIVATORS OF NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE (NAMPT) AND USES THEREOF

Provided herein are small molecule activators of Nicotinamide Phosphoribosyltransferase (NAMPT), compositions comprising the compounds, and methods of using the compounds and compositions.

N-[4-(isopimaric acid acylamino)phenyl]arylsulfonamide compounds and preparation method and anticancer activity application thereof

The invention relates to N-[4-(isopimaric acid acylamino)phenyl]arylsulfonamide compounds and a preparation method and anticancer activity application thereof. The general structural formula of the compounds is shown in the description, wherein Ar represents phenyl or 4-methylphenyl or 4-methoxyphenyl or 4-t-butylphenyl or 4-fluorophenyl or 4-bromophenyl or 3-chlorphenyl or 3-bromophenyl or 2,5-dimethoxyphenyl or 2,4-dichlorophenyl or 5-chloro-2-methoxyphenyl or 5-bromo-2-methoxyphenyl or pentafluorophenyl or the like. With the natural diterpenoid compound isopimaric acid serving as the raw material, the N-[4-(isopimaric acid acylamino)phenyl]arylsulfonamide compounds with the novel structure are prepared according to the reaction characteristics of active groups of the raw material, and the derivatives show high activity in anticancer application and are expected to be applied to the pharmaceutical industry. The compounds and the preparation method have the advantages that reaction conditions are mild, the process is simple, and environmental pollution is hardly caused.

Discovery and Structure-Based Optimization of 2-Ureidothiophene-3-carboxylic Acids as Dual Bacterial RNA Polymerase and Viral Reverse Transcriptase Inhibitors

We are concerned with the development of novel anti-infectives with dual antibacterial and antiretroviral activities for MRSA/HIV-1 co-infection. To achieve this goal, we exploited for the first time the mechanistic function similarity between the bacterial RNA polymerase (RNAP) "switch region" and the viral non-nucleoside reverse transcriptase inhibitor (NNRTI) binding site. Starting from our previously discovered RNAP inhibitors, we managed to develop potent RT inhibitors effective against several resistant HIV-1 strains with maintained or enhanced RNAP inhibitory properties following a structure-based design approach. A quantitative structure-activity relationship (QSAR) analysis revealed distinct molecular features necessary for RT inhibition. Furthermore, mode of action (MoA) studies revealed that these compounds inhibit RT noncompetitively, through a new mechanism via closing of the RT clamp. In addition, the novel RNAP/RT inhibitors are characterized by a potent antibacterial activity against S. aureus and in cellulo antiretroviral activity against NNRTI-resistant strains. In HeLa and HEK 293 cells, the compounds showed only marginal cytotoxicity.