1417403-96-3

Upstream product

• 1943-88-0 2,4-dicyanotoluene 
• 3347-99-7 4-methyl isophthalic acid 
• 23038-61-1 dimethyl 4-methylbenzene-1,3-dicarboxylate 
• 70450-41-8 1-chloro-3-(iodomethyl)benzene 
• 95-73-8 2,4-dichlorotoluene 
• 620-20-2 1-Chloro-3-chloromethyl-benzene 
• 7697-26-9 3-bromo-4-methylbenzoic acid 

Downstream Products

• 1417404-25-1 C₂₆H₂₂F₂N₂O₃ 
• 1417404-26-2 C₂₈H₂₇F₂N₃O₃ 
• 1417404-27-3 8-((3-benzamido-4-fluorophenyl)amino)-N-(2-morpholinoethyl)-5-oxo-10,11-dihydro-5H-dibenzo[a,d][7]annulene-3-carboxamide 
• 1417404-28-4 8-((2,4-difluorophenyl)amino)-5-oxo-10,11-dihydro-5H-dibenzo[a,d][7]annulene-3-carboxylic acid 
• 1417404-29-5 C₂₂H₁₆F₂N₂O₂ 
• 1417404-30-8 C₂₃H₁₈F₂N₂O₂ 
• 1417404-31-9 C₃₀H₃₀F₂N₂O₂ 
• 1417404-32-0 C₂₄H₁₉F₃N₂O₂ 
• 1417404-33-1 C₂₄H₁₉ClF₂N₂O₂ 
• 1417404-34-2 C₂₅H₂₂F₂N₂O₂S 
• 1417404-35-3 C₂₅H₂₂F₂N₂O₃ 
• 1417403-97-4 4-[2-(3-chlorophenyl)ethyl]isophthalic acid 
• 1417404-36-4 C₂₅H₂₂F₂N₂O₄S 
• 1417404-37-5 C₂₄H₂₀F₂N₂O₃ 

Relevant academic research and scientific papers

CENTRALLY ACTIVE P38ALPHA INHIBITING COMPOUNDS

Compounds that are inhibitors of p38alpha and centrally available are described.

Bioisosteric Replacement of Arylamide-Linked Spine Residues with N-Acylhydrazones and Selenophenes as a Design Strategy to Novel Dibenzosuberone Derivatives as Type i 1/2 p38α MAP Kinase Inhibitors

The recent disclosure of type I 1/2 inhibitors for p38α MAPK demonstrated how the stabilization of the R-spine can be used as a strategy to greatly increase the target residence time (TRT) of inhibitors. Herein, for the first time, we describe N-acylhydrazone and selenophene residues as spine motifs, yielding metabolically stable inhibitors with high potency on enzymatic, NanoBRET, and whole blood assays, improved metabolic stability, and prolonged TRT.

Design, Synthesis, and Biological Evaluation of Novel Type I1/2 p38α MAP Kinase Inhibitors with Excellent Selectivity, High Potency, and Prolonged Target Residence Time by Interfering with the R-Spine

We recently reported 1a (skepinone-L) as a type I p38α MAP kinase inhibitor with high potency and excellent selectivity in vitro and in vivo. However, as a type I inhibitor, it is entirely ATP-competitive and shows just a moderate residence time. Thus, the scope was to develop a new class of advanced compounds maintaining the structural binding features of skepinone-L scaffold like inducing a glycine flip at the hinge region and occupying both hydrophobic regions I and II. Extending this scaffold with suitable residues resulted in an interference with the kinase's R-Spine. By synthesizing 69 compounds, we could significantly prolong the target residence time with one example to 3663 s, along with an excellent selectivity score of 0.006 and an outstanding potency of 1.0 nM. This new binding mode was validated by cocrystallization, showing all binding interactions typifying type I1/2 binding. Moreover, microsomal studies showed convenient metabolic stability of the most potent, herein reported representatives.

Dibenzosuberones as p38 mitogen-activated protein kinase inhibitors with low ATP competitiveness and outstanding whole blood activity

p38α mitogen-activated protein (MAP) kinase is a main target in drug research concerning inflammatory diseases. Nevertheless, no inhibitor of p38α MAP kinase has been introduced to the market. This might be attributed to the fact that there is no inhibitor which combines outstanding activity in biological systems and selectivity. Herein an approach to the development of such inhibitors on the basis of the highly selective molecular probe Skepinone-L is described. Introduction of a "deep pocket" moiety addressing the DFG motif led to an increased activity of the compounds. Hydrophilic moieties, addressing the solvent-exposed area adjacent to hydrophilic region II, conserved a high activity of the compounds in a whole blood assay. Combined with their outstanding selectivity and low ATP competitiveness, these inhibitors are very interesting candidates for use in biological systems and in therapy.