18378-20-6

Usage

Chemical Properties

BROWN FINE POWDER

InChI:InChI=1/C13H10N4O3/c18-17(19)11-7-6-10(12-13(11)16-20-15-12)14-8-9-4-2-1-3-5-9/h1-7,14H,8H2

Upstream product

• 10199-89-0 NBD chloride 
• 100-46-9 benzylamine 
• 1635-61-6 5-chloro-2-nitroaniline 
• 1194-66-7 2,6-dichloronitrosobenzene 
• 19155-86-3 5-chlorobenzo[c][1,2,5]oxadiazole 
• 7116-16-7 4-chloro-2,1,3-benzoxadiazole 
• 17348-69-5 5-chlorobenzofurazan-1-oxide 
• 5714-17-0 5-chloro-4-nitrobenzo[c]-[1,2,5]oxadiazole 

Relevant academic research and scientific papers

POTENT ANALOGUES OF THE C-MYC INHIBITOR 10074-G5 WITH IMPROVED CELL PERMEABILITY

The present invention relates compounds and compositions for interfering with the association of Myc and Max. These compounds and compositions are useful in methods for inhibiting growth or proliferation of a cell. Methods of inhibiting growth or proliferation of a cell comprise contacting the cell with an amount of a compound that interferes with Myc and Max association effective to inhibit growth or proliferation of the cell. The compounds exhibit increased inhibitory activity against c-Myc relative to the known c-Myc inhibitor small-molecule benzofurazan N-([1,1′-biphenyl]-2-yl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine (10074-G5).

Pharmacophore identification of c-Myc inhibitor 10074-G5

A structure-activity relationship (SAR) study of the c-Myc (Myc) inhibitor 10074-G5 (N-([1,1′-biphenyl]-2-yl)-7-nitrobenzo[c][1,2,5]oxadiazol-4- amine, 1) - which targets a hydrophobic domain of the Myc oncoprotein that is flanked by arginine residues - was executed in order to determine its pharmacophore. Whilst the 7-nitrobenzofurazan was found to be critical for inhibitory activity, the ortho-biphenyl could be replaced with a para-carboxyphenyl group to furnish the new inhibitor JY-3-094 (3q). Around five times as potent as the lead with an IC50 of 33 μM for disruption of the Myc-Max heterodimer, JY-3-094 demonstrated excellent selectivity over Max-Max homodimers, with no apparent effect at 100 μM. Importantly, the carboxylic acid of JY-3-094 improves the physicochemical properties of the lead compound, which will facilitate the incorporation of additional hydrophobicity that might enhance Myc inhibitory activity further still.

Derivatization of Amines with 4-Substituted 7-Nitrobenzofurazans

Electrophilic derivatives of 4-nitro-benzofurazan with different reactivities were used to synthesize 28 new mono- and disubstituted 4-amino-7-nitrobenzofurazans 2b, 2d, 2f-2i, 2l, 2m-2n, 3b-3f, 3h-3j, 4c-4d, 4f-4k, 4m, 4o-4p.A reaction mechanism is proposed on the basis of the differences of the reactivities and a preliminary kinetic examination.The acid character of the N-H-function in monosubstituted compounds is demonstrated by means of spectroscopical investigation of pKa-values.Data from i.r., u.v./vis, and fluorescence studies are offered.