1. Discovery of nonpeptide 3,4-dihydroquinazoline-4-carboxamides as potent and selective sst2 agonists.
- Author
-
Zhao, Jian, Wang, Shimiao, Han, Sangdon, Kim, Sun Hee, Kusnetzow, Ana Karin, Nguyen, Julie, Rico-Bautista, Elizabeth, Tan, Hannah, Betz, Stephen F., Scott Struthers, R., and Zhu, Yunfei
- Subjects
- *
CARCINOID , *NEUROENDOCRINE tumors , *PHARMACEUTICAL chemistry , *LEAD compounds - Abstract
Nonpeptide sst2 agonists can provide a new treatment option for patients with acromegaly, carcinoid tumors, and neuroendocrine tumors. Our medicinal chemistry efforts have led to the discovery of novel 3,4-dihydroquinazoline-4-carboxamides as sst2 agonists. This class of molecules exhibits excellent human sst2 potency and selectivity against sst1, sst3, sst4 and sst5 receptors. Leading compound 3-(3-chloro-5-methylphenyl)-6-(3-fluoro-2-hydroxyphenyl)-N,7-dimethyl-N-{[(2S)-pyrrolidin-2-yl]methyl}-3,4-dihydroquinazoline-4-carboxamide (28) showed no inhibition of major CYP450 enzymes (2C9, 2C19, 2D6 and 3A4) and weak inhibition of the hERG channel. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF