2227-87-4

Upstream product

• 137-07-5 2-amino-benzenethiol 
• 14393-62-5 2-amino-2',4'-dinitrodiphenyl sulphide 
• 108-24-7 acetic anhydride 
• 97-00-7 1-chloro-2,4-dinitro-benzene 

Downstream Products

• 1393520-11-0 N-(4-bromo-2-((2,4-dinitrophenyl)thio)phenyl)acetamide 
• 1393520-12-1 N-(2-((2,4-dinitrophenyl)thio)-4-iodophenyl)-acetamide 
• 3493-99-0 N-(2,4-dinitro-phenyl)-N-(2-methylsulfanyl-phenyl)-acetamide 

Relevant academic research and scientific papers

TRICYCLIC HETEROAROMATIC COMPOUNDS AS ALPHA-SYNUCLEIN LIGANDS

Derivatives of phenothiazine, phenoxazine, and phenazine compounds and their use as α-synuclein ligands are described. Also described are methods of using these compounds and their radiolabeled analogs for the detection, monitoring, and treatment of synucleinopathies, including Parkinson's disease.

Synthesis and in vitro evaluation of α-synuclein ligands

Accumulation of misfolded α-synuclein in Lewy bodies and Lewy neurites is the pathological hallmark of Parkinson's disease (PD). To identify ligands having high binding potency toward aggregated α-synuclein, we synthesized a series of phenothiazine derivatives and assessed their binding affinity to recombinant α-synuclein fibrils using a fluorescent thioflavin T competition assay. Among 16 new analogues, the in vitro data suggest that compound 11b has high affinity to α-synuclein fibrils (Ki = 32.10 ± 1.25 nM) and compounds 11d, 16a and16b have moderate affinity to α-synuclein fibrils (Ki ≈ 50-100 nM). Further optimization of the structure of these analogues may yield compounds with high affinity and selectivity for aggregated α-synuclein.