Discovery of novel thienopyrimidine derivatives as LRRK2 inhibitors. (21st December 2021)

• Record Type: Journal Article
• Authors: Choi, Changyu; Park, Jiwon; Jang, Soyeon; Kim, Jihyung; Lee, Sohee; Min, Kyung Hoon
• Is Part Of: Bulletin of the Korean Chemical Society. Volume 43:Number 2(2022)
• Page Start: 232
• Page End: 235
• Publication Date: 2021-12-21
• Subjects: LRRK2 inhibitor -- thienopyrimidine -- small molecule -- Structure‐activity relationship; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/bkcs.12450
• Languages: English
• ISSNs: 0253-2964

Abstract

Abstract: Leucine‐rich repeat kinase 2 (LRRK2) is considered a promising therapeutic target for Parkinson's disease, Crohn's disease, and cancer. Despite considerable research, none of these inhibitors are available for clinical application. Herein, we designed and synthesized novel thienopyrimidine derivatives by a bioisosteric replacement and investigated their structure–activity relationships. Thieno[3, 2‐ d ]pyrimidine derivative 22 showed the most potent inhibitory activity and inhibited both wild‐type and G2019S mutant LRRK2 with IC50 values of 30 and 14 nM, respectively. Abstract :