Synthesis and enzyme inhibitory activities of a series of lipidic diamine and aminoalcohol derivatives on cytosolic and secretory phospholipases A2

We have synthesised some lipidic diamines and aminoalcohols and examined their behaviour as inhibitors of secretory and cytosolic PLA2. Some structure–activity relationships considerations have been deduced. Compound 14 was a potent and selective inhibitor of cPLA2 and compound 4 showed a dual inhibitory profile against both types of PLA2 while no cytotoxicity at 10 μM on human neutrophils or on murine macrophage line was observed for both. Scheme 1. Synthesis of lipidic diamine and aminoalcohol derivatives. i: a) EtOOCCl/N-methylmorpholine/THF; b) NaBH4/MeOH. ii) MsCl/Et3N/CH2Cl2. iii. NaN3/DMF. iv. Pd-C/HCCl3, NaBH4/MeOH. v: EtBr (or EtOOCCH2Br)/Et3N/DMF. vi: glutaric anhydride/EtOAc. vii: HCl/THF, Argon. viii: BnCl/NaH/DMF. ix: EtBr (1.2 or 2.2 eq.)/Et3N/DMF. x: succinic (maleic, glutaric) anh./EtOAc. xi: EtOOCCH2Br/Et3N. xii: H2/Pd-C/AcOH. xiii: 10% KOH/MmeOH. xiv: n-C6H13COCl (n-C15H31COCl)/Et2O. xv: TMSCl/PhOH/HCCl3.