Substituted amide derivatives of C4-ageratochromene dimer analog (19) were synthesized through structural modification of precocene-I (4a), isolated from the essential oil of Ageratum conyzoides L. The target compounds (18–20, 23I-VI, 24I-VI, and 25I-VI) were evaluated for their bone-forming effect using osteoblast differentiation assay. Seven compounds (23I, 23II, 23IV, 23VI, 24III, 24VI, and 25VI) presented good activity within 1 pM–1 nM concentration. At 1 pM concentration, the most active compound i.e. 23II showed effective mineralization of osteoblast cells along with expression of osteogenic marker genes viz RUNX 2, BMP-2, and type 1 collagen (Type-1 col) without any toxicity towards osteoblast cells. Single crystal X-ray analysis of 18 and 20 revealed that the core nucleus of these molecules bear phenyl rings in a Trans-stilbenoid system and had a good structural correlation with 17β-estradiol (1) and diethylstilbestrol (DES, 3). In-silico study about 23II showed its structural complementarities with the LBD of estrogen receptor (ER) which indicated possible ER-mediated activity of compounds.

C4-ageratochromene 二聚体类似物 ( 19 ) 的取代酰胺衍生物是通过对从Ageratum conyzoides L的精油中分离得到的precocene-I ( 4a )进行结构修饰而合成的。目标化合物（18 - 20，23I-VI，24I-VI，和25I-VI），用于使用成骨细胞分化测定其骨成形效果进行了评价。七种化合物（23I、23II、23IV、23VI、24III、24VI和25VI）在 1 pM–1 nM 浓度范围内表现出良好的活性。在 1 pM 浓度下，最活跃的化合物即23II显示成骨细胞的有效矿化以及成骨标记基因即RUNX 2，BMP-2和1型胶原蛋白（Type-1 col）的表达，对成骨细胞没有任何毒性。18和20的单晶X射线分析表明，这些分子的核心核带有反式-芪类系统中的苯环，并且与17β-雌二醇（1）和己烯雌酚（DES，3）具有良好的结构相关性。关于23II的计算机研究显示其与雌激素受体 (ER) 的 LBD 的结构互补性，这表明化合物可能具有 ER 介导的活性。