2. Academic Validation
  3. An efficient and concise synthesis of a selective small molecule non-peptide inhibitor of cathepsin L: KGP94

An efficient and concise synthesis of a selective small molecule non-peptide inhibitor of cathepsin L: KGP94

  • Bioorg Chem. 2021 Nov;116:105317. doi: 10.1016/j.bioorg.2021.105317.
Rachakunta Munikishore 1,  Liang-Liang Wang 2,  Shuqun Zhang 1,  Qin-Shi Zhao 1,  Zhili Zuo 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650 201, Yunnan province, People's Republic of China.
  • 2 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650 201, Yunnan province, People's Republic of China. Electronic address: wangliangliang@mail.kib.ac.cn.
  • 3 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650 201, Yunnan province, People's Republic of China. Electronic address: zuozhili@mail.kib.ac.cn.
PMID: 34488126 DOI: 10.1016/j.bioorg.2021.105317
Abstract

KGP94 is a potent, selective, and competitive inhibitor of the lysosomal endopeptidase Enzyme (Cathepsin L) currently in preclinical trials for the treatment of metastatic Cancer, which is a leading cause of cancer-associated death. Herein, we report two new synthetic routes for synthesizing the target compound through four consecutive steps, using a Weinreb amide approach starting from a common 3-bromobenzoyl chloride. A key step in the approach is a coupling reaction of a readily available Grignard reagent with amide 4 to produce 6, a previously unreported coupling pattern. These new strategies offer an efficient and alternative approach to synthesis of target compound with an excellent overall yield.

Keywords

Cathepsin L; KGP94, cancer; gram-scale synthesis; small-molecule inhibitor.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-118762
    99.53%, Cathepsin L Inhibitor