Synthesis and biological activity of the marine-derived leonurine analogue N-(4-guanidinobutyl)-2-(4-hydroxyphenyl)-2-oxoacetamide

N-(4-Guanidinobutyl)-2-(4-hydroxyphenyl)-2-oxoacetamide (C1), a marine-derived leonurine analogue, was synthesized via a six-step route with 38% total yield. Biological evaluation demonstrated potent anticoagulant activity through significant prolongation of APTT (20 mM) and PT (5 mM). C1 dose-dependently (100–200 μM) suppressed LPS-induced NO production in RAW 264.7 macrophages without cytotoxicity and modulated phagocytosis. In LPS-induced acute lung injury rats, C1 reduced proinflammatory cytokines in BALF. These findings highlight C1’s dual anticoagulant and anti-inflammatory properties as a promising lead compound.