4-thiazolidinone derivatives as novel inhibitors of hDHODH

A series of 4-thiazolidinone derivatives have been identified as hDHODH inhibitors. Several compounds exhibited moderate activities against hDHODH, especially compounds 26 and 31 with IC50 values of 1.75 and 1.12 μM, respectively. The SAR study and binding mode investigation demonstrate that the 4-thiazolidinone scaffold, the cyano substitution for R1, the ester structure for R2 and the hydrophobic substitutions at para- or meta-positions of the phenyl group for R are favorable for improving inhibitory activity. For this series of 4-thiazolidinone derivatives, the hydrogen bond with Tyr38 and the water-mediated hydrogen bond with Ala55 were proposed to be indispensable for maintaining the inhibitory activity against hDHODH. The presented SAR indicates that further decoration of the phenyl group at R may provide us more potent hDHODH inhibitors.

User Login


Database


PTID

Contact us


Honglin Li's Lab
Shanghai Key Laboratory of New Drug Design
School of Pharmacy
East China University of Sci. & Tech.
Room 527, Building 18, 130 Meilong Road,
Shanghai, 200237, P. R. China
Tel: (86) 21 6425 0213
Prof. Honglin Li
hlli@ecust.edu.cn

Copyright © 2023 Prof. HongLin Li's Group, School of Pharmacy, East China University of Science & Technology · All Right Reserved.
沪ICP备19004698号-1 |  沪公网安备31011302004713号