Abstract
7H-Pyrrolo[3,2-f]quinazoline-1,3-diamine (1) is a privileged chemical scaffold with significant biological activities. However, the currently accessible chemical space derived from 1 is rather limited. Here we expanded the chemical space related to 1 by developing efficient methods for regioselective monoacylation at N1, N3 and N7, respectively. With this novel methodology, a focused library of mono-N-acylated pyrroloquinazoline-1,3-diamines was prepared and screened for anti-breast cancer activity. The structure-activity relationship (SAR) results showed that N 3-acylated compounds were in general more potent than N 1-acylated compounds while N7-acylation significantly reduced their solubility. Among the compounds evaluated, 7f possessed 8-fold more potent activity than 1 in MDA-MB-468 cells. More importantly, 7f was not toxic to normal human cells. These results suggest that 7f is a novel compound as a potential anti-breast cancer agent without harming normal cells.
Original language | English (US) |
---|---|
Pages (from-to) | 1275-1282 |
Number of pages | 8 |
Journal | MedChemComm |
Volume | 4 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2013 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Pharmacology
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry