口服有效的ADAMTS-4/5抑制剂异吲哚啉酰胺衍生物，可治疗骨关节炎，本研究中部分化合物通过9728太阳集团首页合成

Osteoarthritis (OA) is the most common chronic joint disease that affects the knee or hip with symptoms including joint pain and dysfunction. OA treatment is a highly unmet medical need. Development of a disease-modifying OA drug (DMOAD) is challenging with no approved drugs on the market. Inhibition of ADATMS-4/5 is a promising OA therapeutics to target cartilage degradation and potentially can reduce joint pain and restore its normal function.

Herein, researchers report the discovery and optimization of hydantoin-type ADAMTS-4/5 inhibitors featured by a novel isoindoline amide scaffold for the treatment of osteoarthritis. The most promising compound 18 showed high in vitro potency as an ADAMTS-4/5 inhibitor, good druglike properties, and oral bioavailability. Molecule 18 exhibited clear dose-dependent efficacy in two independent in vivo efficacy studies. Part of the compound synthesis was performed at Medicilon.

Reference:

Peng Zhao, et al. Discovery of Isoindoline Amide Derivatives as Potent and Orally Bioavailable ADAMTS-4/5 Inhibitors for the Treatment of Osteoarthritis. ACS Pharmacol Transl Sci. 2022 Jun 22;5(7):458-467. doi: 10.1021/acsptsci.2c00023.