Synthesis and biological evaluation of novel 2-phenylquinazoline-4-amine derivatives: identification of 6-phenyl-8H-benzo[g]quinazolino[4,3-b]quinazolin-8-one as a highly potent inducer of NAD(P)H quinone oxidoreductase 1

Figures & data

Scheme 1. Formation of 4-aminoquinazolines 2–15.

Figure 1. Dose-response curves for NQO1 inducer activity of novel 2-phenylquinazolin-4-amine derivatives. Data are expressed as the ratio of treated/control (T/C) values.

Table 1. NQO1 inducer potency of novel 2-phenylquinazolin-4-amine derivatives.

Compound number	CD (μM)
2	4.1
3	0.7
4	5.5
5	1.4
6	0.2
7	0.3
8	1.3
9	1.5
10	0.5
11	0.3
12	0.07
13	0.9
14	2.6

The CD value is the Concentration required to Double the specific enzyme activity.

Figure 2. Interaction map of the native ligand in the Kelch domain of Keap 1 (PDB ID: 41QK).

Figure 3. Interaction map of compound 12 in the Kelch domain of Keap 1 (PDB ID: 41QK).