Chemical modification of β-glucocerebrosidase inhibitor N-octyl-β-valienamine: synthesis and biological evaluation of N-alkanoyl and N-alkyl derivatives Original Research Article

Several N-alkanoyl 4a–d and N-alkyl derivatives 5a–g of the potent β-glucocerebrosidase inhibitor N-octyl β-valienamine (3) were synthesized in order to elucidate a role of hydrophobic portion in the inhibitory action. Although the former lacked inhibitory potency, the latter were strong β-glucocerebrosidase inhibitors (cf. N-decyl-N-octyl-β-valienamine 5d: Ki 6.6×10−8 M). Furthermore, when being prescribed into mouse-derived B16 melanoma cells, N-butyl-N-octyl-β-valienamine 5a and 5d were shown to change the amount of GlcCer and GM3, which suggests that they are possibly introduced into cells and influence glycolipids biosynthesis.