1316652-72-8

Upstream product

• 91319-54-9 1-(2-bromoethyl)-2-fluorobenzene 

Downstream Products

• 1316651-99-6 C₁₇H₁₅FN₄O₂ 
• 1602732-49-9 C₂₃H₂₀FN₅O 
• 1602733-68-5 C₂₃H₂₀FN₅O 

Relevant academic research and scientific papers

A versatile strategy for the synthesis of 4,5-dihydroxy-2,3-pentanedione (DPD) and related compounds as potential modulators of bacterial quorum sensing

Resistance to antibiotics is an increasingly serious threat to global public health and its management translates to significant health care costs. The validation of new Gram-negative antibacterial targets as sources for potential new antibiotics remains a challenge for all the scientists working in this field. The interference with bacterial Quorum Sensing (QS) mechanisms represents a potentially interesting approach to control bacterial growth and pursue the next generation of antimicrobials. In this context, our research is focused on the discovery of novel compounds structurally related to (S)-4,5-dihydroxy-2,3-pentanedione, commonly known as (S)-DPD, a small signaling molecule able to modulate bacterial QS in both Gram-negative and Gram-positive bacteria. In this study, a practical and versatile synthesis of racemic DPD is presented. Compared to previously reported syntheses, the proposed strategy is short and robust: it requires only one purification step and avoids the use of expensive or hazardous starting materials as well as the use of specific equipment. It is therefore well suited to the synthesis of derivatives for pharmaceutical research, as demonstrated by four series of novel DPD-related compounds described herein.

Fragment-Based Drug Design Facilitated by Protein-Templated Click Chemistry: Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin

There is an urgent need for the development of efficient methodologies that accelerate drug discovery. We demonstrate that the strategic combination of fragment linking/optimization and protein-templated click chemistry is an efficient and powerful method that accelerates the hit-identification process for the aspartic protease endothiapepsin. The best binder, which inhibits endothiapepsin with an IC50value of 43 μm, represents the first example of triazole-based inhibitors of endothiapepsin. Our strategy could find application on a whole range of drug targets.

Using the same hydroxamic acid derivative and HDAC8 inhibitor (by machine translation)

Disclosed are: a compound which is capable of inhibiting the function of HDAC8; and an HDAC8 inhibitor. Specifically disclosed is a hydroxamic acid derivative which is characterized by being composed of a compound represented by general formula (1) (wherein X represents an aromatic substituent or an optionally substituted 3-8 membered ring, and n represents an integer of 0-20), or a pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof.

Rapid discovery of highly potent and selective inhibitors of histone deacetylase 8 using click chemistry to generate candidate libraries

To find HDAC8-selective inhibitors, we designed a library of HDAC inhibitor candidates, each containing a zinc-binding group that coordinates with the active-site zinc ion, linked via a triazole moiety to a capping structure that interacts with residues on the rim of the active site. These compounds were synthesized by using click chemistry. Screening identified HDAC8-selective inhibitors including C149 (IC50 = 0.070 μM), which was more potent than PCI-34058 (6) (IC50 = 0.31 μM), a known HDAC8 inhibitor. Molecular modeling suggested that the phenylthiomethyl group of C149 binds to a unique hydrophobic pocket of HDAC8, and the orientation of the phenylthiomethyl and hydroxamate moieties (fixed by the triazole moiety) is important for the potency and selectivity. The inhibitors caused selective acetylation of cohesin in cells and exerted growth-inhibitory effects on T-cell lymphoma and neuroblastoma cells (GI50 = 3-80 μM). These findings suggest that HDAC8-selective inhibitors have potential as anticancer agents.