863605-04-3

Upstream product

• 446-35-5 2,4-Difluoronitrobenzene 
• 78-81-9 isobutylamine 

Downstream Products

• 863605-05-4 1-(3-(isobutylamino)-4-nitrophenyl)-2-phenyl-1H-imidazole 
• 1380601-46-6 C₃₁H₄₆N₄O 
• 1380645-60-2 (E)-3-(2-(6-(di-(n-butyl)amino)-1-isobutyl-1H-benzimidazole-2-yl)vinyl)-5,5-dimethylcyclohex-2-enone 
• 1380601-42-2 2-isobutylamino-4-(di-(n-butyl)amino)aniline 

Relevant academic research and scientific papers

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.

A Novel Mechanistic Study on Ultrasound-Assisted, One-Pot Synthesis of Functionalized Benzimidazo[2,1-b]quinazolin-1(1H)-ones

Ultrasound-assisted synthesis of benzimidazo[2,1-b]quinazolin-1(1H)-ones was achieved via piperidine-catalyzed three-component reaction of 2-aminobenzimidazoles, an aromatic aldehyde, and 1,3-dione in aqueous isopropanol. This mechanism was first suspected following our identification of unusual reaction intermediates in a one-pot reaction. An unprecedented coupling reaction, it involved a nucleophilic attack by 2-aminobenzimidazole on in situ generated Michael adduct, followed by electrocyclic ring formation reaction. In contrast to the commonly accepted mechanism, that the direct reaction of 2-amino benzimidazole with a Knoevenagel adduct cannot deliver target compounds.

6-Dialkylaminobenzimidazole nonlinear optical dyes

(Chemical Equation Presented) A new 6-dialkylaminobenzimidazole nonlinear optical dye was synthesized in eight linear steps with an overall yield of 16%.

KINASE INHIBITORS

ABSTRACT The present invention provides kinase inhibitors of Formula I: .