15962-42-2

Upstream product

• 85-44-9 phthalic anhydride 
• 875-74-1 (R)-phenylglycine 

Downstream Products

• 139528-48-6 N-<2-(N-butylamino)-2-phenylethyl>-1,3-dihydroisoindole 
• 135711-20-5 (R)-2-(1,3-Dihydro-isoindol-2-yl)-2-phenyl-ethanol 

Relevant academic research and scientific papers

Synthesis of Rhodium Complexes with Chiral Diene Ligands via Diastereoselective Coordination and Their Application in the Asymmetric Insertion of Diazo Compounds into E?H Bonds

A new method for the synthesis of chiral diene rhodium catalysts is introduced. The readily available racemic tetrafluorobenzobarrelene complexes [(R2-TFB)RhCl]2 were separated into two enantiomers via selective coordination of one of them with the auxiliary S-salicyl-oxazoline ligand. One of the resulting chiral complexes with an exceptionally bulky diene ligand [(R,R-iPr2-TFB)RhCl]2 was an efficient catalyst for the asymmetric insertion of diazoesters into B?H and Si?H bonds giving the functionalized organoboranes and silanes with high yields (79–97 %) and enantiomeric purity (87–98 % ee). The stereoselectivity of separation via auxiliary ligand and that of the catalytic reaction was predicted by DFT calculations.

Design, synthesis and mechanism of novel shikonin derivatives as potent anticancer agents

In this study, a series of novel shikonin derivatives (30-49) were designed and synthesized and their anti-proliferative activities were evaluated against five different cancer cell lines, including HeLa, HepG2, MCF-7, BGC and A549. Some of the compounds show strong anti-proliferative effects against HeLa, HepG2 and MCF-7 with IC50 values ranging from 1.26 to 18.50 μM and show lower side effects towards normal cell lines as compared to shikonin. Compared to other compounds and shikonin itself, compound 40 displayed much stronger anti-proliferative effects against various cancer cell lines. Furthermore, the flow cytometry results demonstrated that compound 40 could obviously induce apoptosis in a dose- and time-dependent manner and also cause cell cycle arrest at the G2/M phase. For further investigation of the aforementioned mechanisms, we performed Western blot experiments and found that the cleavage of PARP and upstream caspase-3 increased; moreover, caspase-9 was activated by cleavage but not caspase-8. These aforementioned results also indicate that compound 40 could induce caspase-9 involved apoptosis and G2/M phase cell cycle arrest via the P21, p-CDC2 (Tyr15) pathway independent of P53.

Targeting Her2-insYVMA with Covalent Inhibitors - A Focused Compound Screening and Structure-Based Design Approach

Mutated or amplified Her2 serves as a driver of non-small cell lung cancer or mediates resistance toward the inhibition of its family member epidermal growth factor receptor with small-molecule inhibitors. To date, small-molecule inhibitors targeting Her2 which can be used in clinical routine are lacking, and therefore, the development of novel inhibitors was undertaken. In this study, the well-established pyrrolopyrimidine scaffold was modified with structural motifs identified from a screening campaign with more than 1600 compounds, which were applied against wild-type Her2 and its mutant variant Her2-A775_G776insYVMA. The resulting inhibitors were designed to covalently target a reactive cysteine in the binding site of Her2 and were further optimized by means of structure-based drug design utilizing a set of obtained complex crystal structures. In addition, the analysis of binding kinetics and absorption, distribution, metabolism, and excretion parameters as well as mass spectrometry experiments and western blot analysis substantiated our approach.

Cyclic amides

Cyclic amides are inhibitors of tumor necrosis factor and can be used to combat cachexia, endotoxic shock, and retrovirus replication. A typical embodiment is 3-phenyl-3-(1-oxoisoindolin-2-yl)propionamide.