19088-99-4

Upstream product

• 4771-47-5 3-chloro-2-nitro-benzoic acid 

Downstream Products

• 59772-47-3 3-chloro-2-nitrobenzamide 
• 173589-73-6 3-chloro-N-(4-chloro-phenyl)-2-nitro-benzamide 
• 626606-14-2 2-(3-chloro-2-nitrophenyl)-4-methyl-1H-benzimidazole 
• 77158-86-2 (3-chloro-2-nitrophenyl)methanol 
• 925454-57-5 N-(2-Carbamoyl-phenyl)-3-chloro-2-nitro-benzamide 
• 22233-52-9 3-chloro-2-nitrobenzaldehyde 
• 714229-96-6 2-(3-chloro-2-nitro-phenyl)-thiochromen-4-one 
• 714229-86-4 2-(3-chloro-2-nitro-phenyl)-3-methanesulfinyl-thiochroman-4-one 
• 714229-78-4 1-[2-(p-methoxybenzylthio)phenyl]-2-(methylsulfinyl)-3-(3-chloro-2-nitrophenyl)-2-propen-1-one 
• 626606-18-6 2-(3-chloro-2-nitrophenyl)-1H-benzimidazole 
• 626606-24-4 1-allyl-2-(3-chloro-2-nitrophenyl)-1H-benzimidazole 
• 626606-21-1 1-allyl-2-(3-chloro-2-nitrophenyl)-4-methylbenzimidazole 
• 626606-00-6 1-[2-(3-chloro-2-nitrophenyl)-4-methylbenzimidazol-1-yl]-3,3-dimethylbutan-2-ol 
• 661487-42-9 (S)-1-(3-Chloro-2-nitro-benzoyl)-pyrrolidine-2-carbaldehyde 

Relevant academic research and scientific papers

Synthesis and structure-activity relationship studies of n-monosubstituted aroylthioureas as urease inhibitors

Background: Thiourea is a classical urease inhibitor which is usually used as a positive control, and many N,N'-disubstituted thioureas have been determined as urease inhibitors. However, due to steric hindrance, N,N'-disubstituted thiourea motif could not bind urease as thiourea. On the contrary, N-monosubstituted thiourea with a tiny thiourea motif could theoretically bind into the active pocket as thiourea. Objective: A series of N-monosubstituted aroylthioureas were designed and synthesized for evaluation as urease inhibitors. Methods: Urease inhibition was determined by the indophenol method and IC50 values were calculated using computerized linear regression analysis of quantal log dose-probit functions. The kinetic parameters were estimated via surface plasmon resonance (SPR) and by nonlinear regression analysis based on the mixed type inhibition model derived from Michaelis-Menten kinetics. Results: Compounds b2, b11, and b19 reversibly inhibited urease with a mixed mechanism, and showed excellent potency against both cell-free urease and urease in the intact cell, with IC50 values being 90-to 450-fold and 5-to 50-fold lower than the positive control acetohydroxamic acid, respectively. The most potent compound b11 showed an IC50 value of 0.060 ± 0.004μM against cell-free urease, which bound to urea binding site with a very low KD value (0.420±0.003nM) and a very long residence time (6.7 min). Compound b11 was also demonstrated to have very low cytotoxicity to mammalian cells. Conclusion: The results revealed that N-monosubstituted aroylthioureas bound to the active site of urease as expected, and represent a new class of urease inhibitors for the development of potential therapeutics against infections caused by urease-containing pathogens.

One-Pot Synthesis of Seven-Membered Heterocyclic Derivatives of Diazepines Involving Copper-Catalyzed Rearrangement Cascade Allyl-Amination

A novel and efficient method has been proposed for the synthesis of 1,4-benzodiazepine-5-ones from o-nitrobenzoic N-allylamides by using molybdenyl acetylacetonate and copper(II) trifluoromethanesulfonate as catalysts in the presence of triphenylphosphine. This synthesis process involves nitrene formation, C-H bond insertion, C≠C bond rearrangement, and C-N bond formation cascade reactions via copper- and molybdenum-catalyzed mediation. The method features a wide substrate scope and a moderate to high yield (up to 90%), exhibiting the possibility for practical applications.

SMALL MOLECULE INHIBITORS OF CANCER STEM CELLS AND MESENCHYMAL CANCER TYPES

The present disclosure provides compounds, their pharmaceutical compositions, and methods of their use for treating mesenchymally-derived or mesenchymallytransformed cancers, such as breast cancers and sarcomas, and for treating diseases or disorders that are characterized by the expression of vimentin.

Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo

The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Commun. 2014, 450, 1063). Herein, we establish structure-activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL. However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo.

Extending the structure-activity relationship of anthranilic acid derivatives as farnesoid x receptor modulators: Development of a highly potent partial farnesoid x receptor agonist

The ligand activated transcription factor nuclear farnesoid X receptor (FXR) is involved as a regulator in many metabolic pathways including bile acid and glucose homeostasis. Therefore, pharmacological activation of FXR seems a valuable therapeutic approach for several conditions including metabolic diseases linked to insulin resistance, liver disorders such as primary biliary cirrhosis or nonalcoholic steatohepatitis, and certain forms of cancer. The available FXR agonists, however, activate the receptor to the full extent which might be disadvantageous over a longer time period. Hence, partial FXR activators are required for long-term treatment of metabolic disorders. We here report the SAR of anthranilic acid derivatives as FXR modulators and development, synthesis, and characterization of compound 51, which is a highly potent partial FXR agonist in a reporter gene assay with an EC50 value of 8 ± 3 nM and on mRNA level in liver cells.

QUINAZOLINE DERIVATIVES AS PDE10A ENZYME INHIBITORS

This invention is directed to compounds, which are PDE10A enzyme inhibitors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. The pr

Efficient synthesis of naturally occurring skeleton 5-7-6 tricyclic pyrrolo[2,1- c ][1,4]benzodiazepin-5-one and its derivatives via cationic π-cyclization

An efficient method for the synthesis of a library based on the naturally occurring 5-7-6 tricyclic 5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one skeleton and its derivatives via cationic π-(7-endo) cyclization is described. Georg Thieme Verlag Stuttgart - New York.

Intermolecular SNAr of the heterocycle-activated nitro and fluoro groups-application in the synthesis of polyazamacrocyclic ligands

A new class of tetracylic benzimidazole compounds and derivatives thereof. Additionally provided is a synthetic route for the generation of these and related compounds via Intramolecular Aromatic Nucleophilic Substitution (SNAr) of the Benzimid

Computational study on hydroxybenzotriazoles as reagents for ester hydrolysis

1-Hydroxybenzotriazole (1) and several of its derivatives (2-5) demonstrate potent esterolytic activity toward activated esters such as p-nitrophenyl diphenyl phosphate (PNPDPP) and p-nitrophenyl hexanoate (PNPH) in cationic micelles at pH 8.2 and 25 °C. The deprotonated anionic forms of such reagents act as reactive species in the hydrolysis of ester. To rationalize the origin of their nucleophilic character, a detailed ab initio/DFT computational study has been performed on 1-5 along with additional hydroxybenzotriazole derivatives (6-13). The geometries of 1-hydroxybenzotriazoles (1-13) and their corresponding bases are discussed in detail. All calculations were carried out using different methods, i.e., restricted Hartree-Fock (RHF) and hybrid ab initio/DFT (B3LYP) using 6-31G* and 6-31+G* basis sets. Free energy of protonation ("fep") of the 1-hydroxybenzotriazoles (1-13), free energy of solvation ΔGaq, and the corresponding pKa values have been calculated, Solvation-free energies were calculated using density functional theory and the polarizable continuum model. In addition, to examine the reliability of calculated fep, benzaldehyde oxime (14) and 2-methyl propionaldehyde oxime (15) have been computed as reference systems using different methods and basis sets, the experimental feps of which are known. Our experimental finding shows that the compound 4 is the most effective catalyst for the hydrolytic cleavages of PNPDPP and PNPH, This has been predicted from our calculated fep, pKa, and natural charge analysis results as well. In general, the introduction of electron-withdrawing substituents on 1-hydroxybenzotriazoles facilitates the lowering of pKa and fep. As the pKa values are lowered, a greater percentage of such hydroxybenzotriazoles remain in their deprotonated, anionic forms at pH 8.2. Since the anionic forms are nucleophilic, pKa lowering should enhance their ester cleaving capacity. However, such substitution also decreases the charge density on the catalytically active oxido atom (O7). Taking these two factors together, the derivatives are only modestly better nucleophiles in comparison to the parent 1-hydroxybenzotriazole. Interestingly, the introduction of electron-donating groups does not significantly enhance the charge accumulation on the oxido atom (O7) of 1- hydroxybenzotriazoles.

Design and synthesis of pyrrolo[2,1-c][1,4]benzodiazepine (PBD)- polyaminoalkyl conjugates by the use of SNAr reaction of 2-nitro-5-fluorobenzoate precursor as key reaction

The design and synthesis of a series of pyrrolo[2,1-c][1,4]benzodiazepine (PBD)- polyaminoalkyl conjugates as DNA minor groove binders are described. To introduce polyaminoalkyl groups to the pyrrolo[2,1-c][1,4]benzodiazepine pharmacophore, SNA