131885-34-2

Upstream product

• 446-35-5 2,4-Difluoronitrobenzene 
• 100-46-9 benzylamine 
• 700-36-7 2-bromo-4-fluoronitrobenzene 

Downstream Products

• 1250244-09-7 N¹-benzyl-5-fluorobenzene-1,2-diamine 
• 346704-07-2 benzyl-(2-nitro-5-piperazin-1-yl-phenyl)-amine 
• 951666-39-0 methyl 5-(3-benzylamino-4-nitro-phenoxy)-2-(toluene-4-sulfonylamino)-benzoate 

Relevant academic research and scientific papers

Discovery of 5-(4-methylpiperazin-1-yl)-2-nitroaniline derivatives as a new class of SIRT6 inhibitors

SIRT6 is a deacetylase of histone H3 and inhibitors of SIRT6 have been thought as potential agents for treatment of diabetes. Herein we report the discovery of a series of new SIRT6 inhibitors containing the skeleton 1-phenylpiperazine. Among them, compound 5-(4-methylpiperazin-1-yl)-2-nitroaniline (6d) is the most potent one, which showed an IC50 value of 4.93 μM against SIRT6 in the Fluor de Lys (FDL) assay. It displayed KD values of 9.76 μM and 10 μM in surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) assays, respectively. In selectivity assay, 6d showed no activity against other members of the HDAC family (SIRT1-3 and HDAC1-11) at concentrations up to 200 μM. In a mouse model of type 2 diabetes, 6d could significantly increase the level of glucose transporter GLUT-1, thereby reducing blood glucose. Overall, this study provides a promising lead compound for subsequent drug discovery targeting SIRT6.

From methylene bridged diindole to carbonyl linked benzimidazoleindole: Development of potent and metabolically stable PCSK9 modulators

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently validated therapeutic target for lowering low-density lipoprotein cholesterol (LDL-C). Through phenotypic screening, we previously discovered a class of small-molecules with a 2,3′-diindolymethane (DIM) skeleton that can decrease the expression of PCSK9. But these compounds have low potency and low metabolically stability. After performing structure-activity relationship (SAR) optimization by nitrogen scan, deuterium substitution and fluorine scan, we identified a series of much more potent and metabolically stable PCSK9 modulators. A preliminary in vivo pharmacokinetic study was performed for representative analogues difluorodiindolyketone (DFDIK) 12 and difluorobenzoimidazolylindolylketone (DFBIIK-1) 13. The in vitro metabolic stability correlate well with the in vivo data. The most potent compound 21 has the EC50 of 0.15 nM. Our SAR studies also indicated that the NH on the indole ring of 21 can tolerate more function groups, which may facilitate the mechanism of action studies and also allow further improvement of the pharmacological properties.

Discovery and Characterization of 2-Nitro-5-(4-(phenylsulfonyl)piperazin-1-yl)- N-(pyridin-4-ylmethyl)anilines as Novel Inhibitors of the Aedes aegypti Kir1 (AeKir1) Channel

Mosquito-borne arboviral diseases such as Zika, dengue fever, and chikungunya are transmitted to humans by infected adult female Aedes aegypti mosquitoes and affect a large portion of the world's population. The Kir1 channel in Ae. aegypti (AeKir1) is an important ion channel in the functioning of mosquito Malpighian (renal) tubules and one that can be manipulated in order to disrupt excretory functions in mosquitoes. We have previously reported the discovery of various scaffolds that are active against the AeKir1 channel. Herein we report the synthesis and biological characterization of a new 2-nitro-5-(4-(phenylsulfonyl) piperazin-1-yl)-N-(pyridin-4-ylmethyl)anilines scaffold as inhibitors of AeKir1. This new scaffold is more potent in vitro compared to the previously reported scaffolds, and the molecules kill mosquito larvae.

METALLOENZYME INHIBITOR COMPOUNDS

The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

PYRIDINONES

The present invention encompasses compounds of general formula (I) wherein the groups R1 to R3 and X1 through X6 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.

PYRIDINONES

The present invention encompasses compounds of general formula (I) wherein the groups R1 to R3 and X1 through X6 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.

Nonpolar solvent a key for highly regioselective SNAr reaction in the case of 2,4-difluoronitrobenzene

A practical and highly regioselective aromatic nucleophilic substitution reaction for the substrate 2,4-difluoronitrobenzene is demonstrated with various O/S/N-nucleophiles. Solvent screens substantiate the role of a nonpolar solvent in ortho-selective nucleophilic substitution through a six-membered polar transition state.

HOMOGENEOUS TIME RESOLVED FLUORESCENCE BASED TEST SYSTEM

The present invention concerns a fluorescence resonance energy transfer based high throughput test system to measure the formation of the HIV gp41 six-helix bundle. In a first embodiment the current invention relates to a homogeneous time resolved fluorescence-based test system comprising a first helical polypeptide consisting essentially of the sequence of IQN36 (SEQ ID NO:1); a second helical polypeptide consisting essentially of the sequence of C34 (SEQ ID NO: 2) wherein said IQN36 is labeled with a light emitting fluorophore and said C34 is labeled with an ultra-violet excitable fluorophore.