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PDBsum entry 5l3a
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References listed in PDB file
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Key reference
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Title
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Fragment-Based discovery of 6-Arylindazole jak inhibitors.
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Authors
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A.Ritzén,
M.D.Sørensen,
K.N.Dack,
D.R.Greve,
A.Jerre,
M.A.Carnerup,
K.A.Rytved,
J.Bagger-Bahnsen.
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Ref.
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Acs Med Chem Lett, 2016,
7,
641-646.
[DOI no: ]
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PubMed id
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Abstract
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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.
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