2 research outputs found
Continuous Flow Nucleophilic Aromatic Substitution with Dimethylamine Generated in Situ by Decomposition of DMF
A safe, practical, and scalable continuous
flow protocol for the
in situ generation of dimethylamine from DMF followed by nucleophilic
aromatic substitution of a broad range of aromatic and heteroaromatic
halides is reported
Fragment-Based Discovery of 6‑Arylindazole JAK Inhibitors
Janus kinase (JAK) inhibitors are
emerging as novel and efficacious
drugs for treating psoriasis and other inflammatory skin disorders,
but their full potential is hampered by systemic side effects. To
overcome this limitation, we set out to discover soft drug JAK inhibitors
for topical use. A fragment screen yielded an indazole hit that was
elaborated into a potent JAK inhibitor using structure-based design.
Growing the fragment by installing a phenol moiety in the 6-position
afforded a greatly improved potency. Fine-tuning the substituents
on the phenol and sulfonamide moieties afforded a set of compounds
with lead-like properties, but they were found to be phototoxic and
unstable in the presence of light