Novel Concept for Super-Soft Topical Drugs: Deactivation by an Enzyme-Induced Switch into an Inactive Conformation.
ACS Med Chem Lett
; 14(6): 841-845, 2023 Jun 08.
Article
em En
| MEDLINE
| ID: mdl-37312861
ABSTRACT
We present a novel concept for the design of supersoft topical drugs. Enzymatic cleavage of the carbonate ester of the potent pan Janus kinase (JAK) inhibitor 2 releases hydroxypyridine 3. Due to hydroxypyridine-pyridone tautomerism, 3 undergoes a rapid conformational change preventing the compound to assume the bioactive conformation required for binding to JAK kinases. We demonstrate that the hydrolysis in human blood and the subsequent shape change lead to the deactivation of 2.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Ano de publicação:
2023
Tipo de documento:
Article
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