7661-53-2

Upstream product

• 56-81-5 glycerol 
• 1821-39-2 2-propylaniline 
• 16567-18-3 8-bromoquinoline 
• 22971-32-0 1-(pyridin-2-yl)butan-1-one 
• 927-77-5 n-propylmagnesium bromide 

Relevant academic research and scientific papers

Design and development of photoswitchable DFG-Out RET kinase inhibitors

REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase that is required for development of multiple human tissues, but which is also an important contributor to human cancers. RET activation through rearrangement or point mutations occurs in thyroid and lung cancers. Furthermore, activation of wild type RET is an increasingly recognized mechanism promoting tumor growth and dissemination of a much broader group of cancers. RET is therefore an attractive therapeutic target for small-molecule kinase inhibitors. Non-invasive control of RET signaling with light offers the promise of unveiling its complex spatiotemporal dynamics in vivo. In this work, photoswitchable DFG-out RET kinase inhibitors based on heterocycle-derived azobenzenes were developed, enabling photonic control of RET activity. Based on the binding mode of DFG-out kinase inhibitors and using RET kinase as the test model, we developed a photoswitchable inhibitor with a quinoline “head” constituting the azoheteroarene. This azo compound was further modified by three different strategies to increase the difference in biological activity between the E-isomer and the light enriched Z-isomer. Stilbene-based derivatives were used as model compounds to guide in the selection of substituents that could eventually be introduced to the corresponding azo compounds. The most promising quinoline-based compound showed more than a 15-fold difference in bioactivity between the two isomers in a biochemical assay. However, the same compound showed a decreased Z/E (IC50) ratio in the cellular assay, tentatively assigned to stability issues. The corresponding stilbene compound gave a Z/E (IC50) ratio well above 100, consistent with that measured in the biochemical assay. Ultimately, a 7-azaindole based photoswitchable DFG-out kinase inhibitor was shown to display more than a 10-fold difference in bioactivity between the two isomers, in both a biochemical and a cell-based assay, as well as excellent stability even under reducing conditions.

Non-electronic aromatic ring activation by simple steric repulsion between substituents in 1-methylquinolinium salt systems

A systematic study of non-electronic activation of an aromatic ring was performed using a series of 8-substituted 1-methylquinolinium salts. As the 8-substituent became bulkier, the quinoline framework was distorted by steric repulsion between substituents at the 1- A nd 8-positions. This was accompanied by lack of coplanarity, which brought about dearomatization. Consequently, quinolinium ions possessing a bulky 8-substituent exhibited high reactivity undergoing nucleophilic addition at the 2-position efficiently. We demonstrate that the activation was achieved sterically and not electronically.

Catalytic Enantioselective Methylene C(sp3)?H Amidation of 8-Alkylquinolines Using a Cp*RhIII/Chiral Carboxylic Acid System

Catalytic enantioselective directed methylene C(sp3)?H amidation reactions of 8-alkylquinolines using a Cp*RhIII/chiral carboxylic acid (CCA) hybrid catalytic system are described. A binaphthyl-based chiral carboxylic acid efficiently differentiates between the enantiotopic methylene C?H bonds, which leads to the formation of C?N bonds with good enantioselectivity.

Pd-Catalyzed Alkylation of (Iso)quinolines and Arenes: 2-Acylpyridine Compounds as Alkylation Reagents

The first Pd-catalyzed alkylation of (iso)quinolines and arenes is reported. The readily available and bench-stable 2-acylpyridine compounds were used as an alkylation reagent to form the structurally versatile alkylated (iso)quinolines and arenes. The method affords a convenient pathway for the introduction of alkyl groups into organic molecules.