Discovery and optimization of pyrazolopyrimidine sulfamates as ATG7 inhibitors

• Published in: Bioorganic & medicinal chemistry Vol. 28; no. 19; pp. 115681 - 115701
• Main Authors: Huang, Shih-Chung, Adhikari, Sharmila, Brownell, James E., Calderwood, Emily F., Chouitar, Jouhara, D'Amore, Natalie Roy, England, Dylan B., Foley, Klaudia, Harrison, Sean J., LeRoy, Patrick J., Lok, David, Lublinsky, Anna, Ma, Li-Ting, Menon, Saurabh, Yang, Yu, Zhang, Ji, Gould, Alexandra E.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.10.2020; Elsevier
• Subjects: ATG7; ATG7 inhibitor; Autophagy; Autophagy - drug effects; Autophagy-Related Protein 7 - antagonists & inhibitors; Autophagy-Related Protein 7 - metabolism; Biochemistry & Molecular Biology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Dose-Response Relationship, Drug; Drug Discovery; E1 enzyme; HEK293 Cells; Humans; Life Sciences & Biomedicine; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Science & Technology; Structure-Activity Relationship; Sulfonic Acids - chemical synthesis; Sulfonic Acids - chemistry; Sulfonic Acids - pharmacology; ATG7 inhibitor; ATG7; Autophagy; E1 enzyme; UBIQUITIN

[Display omitted] Autophagy is postulated to be required by cancer cells to survive periods of metabolic and/or hypoxic stress. ATG7 is the E1 enzyme that is required for activation of Ubl conjugation pathways involved in autophagosome formation. This article describes the design and optimization of...