5367-66-8

Usage

Uses

Used in Pharmaceutical Industry:
2-(4-METHYLPIPERAZIN-1-YL)-5-NITROANILINE is used as a building block or intermediate in the synthesis of various pharmaceutical compounds, leveraging its unique chemical structure and properties for the development of new drugs.
Used in Chemical Research:
In the field of chemical research, 2-(4-METHYLPIPERAZIN-1-YL)-5-NITROANILINE serves as a versatile compound for studying the effects of structural modifications on chemical and biological properties, contributing to the advancement of organic synthesis and understanding of molecular interactions.

InChI:InChI=1/C11H16N4O2/c1-13-4-6-14(7-5-13)11-3-2-9(15(16)17)8-10(11)12/h2-3,8H,4-7,12H2,1H3

Upstream product

• 109-01-3 1-methyl-piperazine 
• 369-36-8 6-fluoro-3-nitroaniline 

Downstream Products

• 1629584-89-9 N-(5-amino-2-(4-methylpiperazin-1-yl)phenyl)acrylamide 
• 1629585-04-1 N-(2-(4-methylpiperazin-1-yl)-5-nitrophenyl)acrylamide 
• 1214924-41-0 2-chloro-N-(2-(4-methylpiperazin-1-yl)-5-nitrophenyl)acetamide 
• 1214923-89-3 2-bromo-N-[2-(4-methylpiperazin-1-yl)-5-nitrophenyl]acetamide 

Relevant academic research and scientific papers

Discovery of DDO-2213 as a Potent and Orally Bioavailable Inhibitor of the WDR5-Mixed Lineage Leukemia 1 Protein-Protein Interaction for the Treatment of MLL Fusion Leukemia

WD repeat-containing protein 5 (WDR5) is essential for the stability and methyltransferase activity of the mixed lineage leukemia 1 (MLL1) complex. Dysregulation of theMLL1gene is associated with human acute leukemias, and the direct disruption of the WDR5-MLL1 protein-protein interaction (PPI) is emerging as an alternative strategy for MLL-rearranged cancers. Here, we represent a new aniline pyrimidine scaffold for WDR5-MLL1 inhibitors. A comprehensive structure-activity analysis identified a potent inhibitor 63 (DDO-2213), with an IC50of 29 nM in a competitive fluorescence polarization assay and aKdvalue of 72.9 nM for the WDR5 protein. Compound 63 selectively inhibited MLL histone methyltransferase activity and the proliferation of MLL translocation-harboring cells. Furthermore, 63 displayed good pharmacokinetic properties and suppressed the growth of MV4-11 xenograft tumors in mice after oral administration, first verifying thein vivoefficacy of targeting the WDR5-MLL1 PPI by small molecules.

Aniline WDR5 protein-protein interaction inhibitor as well as preparation method and application thereof

The invention discloses a WDR5 protein-protein interaction inhibitor. The WDR5 protein-protein interaction inhibitor comprises a compound with a structure shown as a general formula (I). Experiments show that the inhibitor acts on WDR5 protein and interacting proteins thereof including but not limited to MLL, selectively inhibits the proliferation of leukemia cells, inhibits the methylation of H3K4 and the expression of downstream Hox/Meis-1 at the cell level. The invention also discloses a preparation method of the inhibitor as well as an application in preparing drugs for treating acute leukemia and other related diseases. (Shown in the description).

Amides, preparation method and medical use thereof

The invention relates to the field of pharmaceutical chemistry, particularly a group of amide compounds (I) and a preparation method therefor and use thereof. Pharmacodynamic experiments prove that the compounds of the invention can be used for preparing medicines for treating leukemia. The formula (I) is shown in the description.

Structure-Based Optimization of a Small Molecule Antagonist of the Interaction between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1)

WD repeat-containing protein 5 (WDR5) is an important component of the multiprotein complex essential for activating mixed-lineage leukemia 1 (MLL1). Rearrangement of the MLL1 gene is associated with onset and progression of acute myeloid and lymphoblastic leukemias, and targeting the WDR5-MLL1 interaction may result in new cancer therapeutics. Our previous work showed that binding of small molecule ligands to WDR5 can modulate its interaction with MLL1, suppressing MLL1 methyltransferase activity. Initial structure-activity relationship studies identified N-(2-(4-methylpiperazin-1-yl)-5-substituted-phenyl) benzamides as potent and selective antagonists of this protein-protein interaction. Guided by crystal structure data and supported by in silico library design, we optimized the scaffold by varying the C-1 benzamide and C-5 substituents. This allowed us to develop the first highly potent (Kdisp 100 nM) small molecule antagonists of the WDR5-MLL1 interaction and demonstrate that N-(4-(4-methylpiperazin-1-yl)-3′-(morpholinomethyl)-[1,1′-biphenyl]-3-yl)-6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide 16d (OICR-9429) is a potent and selective chemical probe suitable to help dissect the biological role of WDR5.

Structure-based design and synthesis of small molecular inhibitors disturbing the interaction of MLL1-WDR5

MLL1 complex catalyzes the methylation of H3K4, and plays important roles in the development of acute leukemia harboring MLL fusion proteins. Targeting MLL1-WDR5 protein-protein interaction (PPI) to inhibit the activity of histone methyltransferase of MLL1 complex is a novel strategy for treating of acute leukemia. WDR5-47 (IC50 = 0.3 μM) was defined as a potent small molecule to disturb the interaction of MLL1-WDR5. Here, we described structure-based design and synthesis of small molecular inhibitors to block MLL1-WDR5 PPI. Especially, compound 23 (IC50 = 104 nM) was the most potent small molecular, and about 3-times more potent than WDR5-47. We also discussed the SAR of these series of compounds with docking study, which may stimulate more potent compounds.

MK2 INHIBITORS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.