Deuterium Editing of Small Molecules: A Case Study on Antitumor Activity of 1,4-Benzodiazepine-2,5-dione Derivatives.
J Med Chem
; 67(15): 12835-12854, 2024 Aug 08.
Article
in En
| MEDLINE
| ID: mdl-39026395
ABSTRACT
Substituting hydrogen with deuterium in drug molecules is an appealing bioisosteric strategy for the generation of novel chemical entities in drug development. Optimizing lead compounds through deuteration has proven to be challenging and unpredictable, particularly for compounds with multiple metabolic sites. This study presents the pioneering achievement of substituting up to 19 hydrogen atoms with deuterium on 1,4-benzodiazepine-2,5-dione derivatives, shedding light on the structure-metabolism relationship and the impact of multiple deuterations on drug-like properties. Notably, the deuterated compound 3f exhibited remarkable antitumor activity in vivo and demonstrated favorable drug-like properties as a drug candidate.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Deuterium
/
Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2024
Document type:
Article