Discovery of 3,5-Dimethyl-4-Sulfonyl‑1H‑Pyrrole-Based Myeloid Cell Leukemia 1 Inhibitors with High Affinity, Selectivity, and Oral Bioavailability

• Published in: Journal of medicinal chemistry Vol. 64; no. 15; pp. 11330 - 11353
• Main Authors: Zhu, Peng-Ju, Yu, Ze-Zhou, Lv, Yi-Fei, Zhao, Jing-Long, Tong, Yuan-Yuan, You, Qi-Dong, Jiang, Zheng-Yu
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 12.08.2021; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; SURVIVAL; ANTI-APOPTOTIC MCL-1; TARGETING MCL-1; IN-VITRO; POTENT; SMALL-MOLECULE; MITOCHONDRIA; CLEAVAGE; FRAGMENT-BASED METHODS; STRUCTURE-BASED DESIGN

Myeloid cell leukemia 1 (Mcl-1) protein is a key negative regulator of apoptosis, and developing Mcl-1 inhibitors has been an attractive strategy for cancer therapy. Herein, we describe the rational design, synthesis, and structure–activity relationship study of 3,5-dimethyl-4-sulfonyl-1H-pyrrole-ba...