Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 7, Issue 6, Pages 641-646Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.6b00087
Keywords
Fragments; JAK inhibitors; psoriasis; indazoles; phototoxicity
Categories
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available