title: Discovery of a Potent Anti-tumor Agent through Regioselective Mono-N-acylation of 7H-Pyrrolo[3,2-f]quinazoline-1,3-diamine.
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 from1is rather limited. Here we expanded the chemical space related to1by developing efficient methods for regioselective monoacylation atN1,N3andN7, respectively. With this novel methodology, a focused library of mono-N-acylated pyrroloquinazoline-1,3-diamines were prepared and screened for anti-breast cancer activity. The structure-activity relationship (SAR) results showed thatN3-acylated compounds were in general more potent thanN1-acylated compounds whileN7-acylation significantly reduced their solubility. Among the compounds evaluated,7fpossessed 8-fold more potent activity than1in MDA-MB-468 cells. More importantly,7fwas not toxic to normal human cells. These results suggest that7fis a novel compound as a potential anti-breast cancer agent without harming normal cells.
authors.affiliation: Program in Chemical Biology, Department of Physiology and Pharmacology, Knight Cancer Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
authors.forename: Jingjin
authors.initials: J
authors.lastname: Chen
authors.forename: Alina
authors.initials: A
authors.lastname: Kassenbrock
authors.forename: Bingbing X
authors.initials: BX
authors.lastname: Li
authors.forename: Xiangshu
authors.initials: X
authors.lastname: Xiao