2-(4-alkylpiperazin-1-yl)quinolines as a new class of imidazole-free histamine H3 receptor antagonists

With the aim of identifying structurally novel, centrally acting histamine H(3) antagonists, a series of 2-(4-alkylpiperazin-1-yl)quinolines was prepared. Systematic variation of the substituents led to highly potent histamine H(3) antagonists with low polar surface area and appropriate log P for blood-brain barrier penetration.