Synthesis of quinolinylaminopyrimidines and quinazolinylmethylaminopyrimidines with antiproliferative activity against melanoma cell line

Figures & data

Figure 1. Structures of Sorafenib, Vemurafenib, and the target compounds.

Scheme 1. Reagents and reaction conditions: (i) HNO₃, H₂SO₄, rt, 4 h; (ii) NaO^tBu, DMF, rt, 4 h; (iii) 5% Pd/C, H₂, MeOH, rt, 1 h; (iv) Pd(OAc)₂, BINAP, CsCO₃, toluene, reflux, 6 h.

Scheme 2. Reagents and reaction conditions: (i) formamidine acetate, HCONH₂, 160 °C, 12 h; (ii) N-bromosuccinimide, AIBN, CCl₄, rt, 24 h; (iii) POCl₃, N,N-dimethylaniline, toluene, reflux, 4 h; (iv) methylamine, THF, rt, 12 h; (v) NaO^tBu, DMF, rt, 4 h.

Table 1. Antiproliferative activity of quinolinylaminopyrimidines 1a–k against A375P human melanoma cell line.

Table 2. Antiproliferative activity of quinazolinylmethylaminopyrimidines 2a–i against A375P human melanoma cell line.

Figure 2. Western blot analyses of p-MEK 1/2 and p-ERK 1/2 expression in presence of compound 1h and Sorafenib.