N-[3’,3’-双(膦羧基)丙基]-3-{4-[双(2-氯乙基)氨基]苯基}-3-氨基丙酰胺的合成及表征

Synthesis and bone-targeted study of N-[3',3'-di(phosphonoxy)propyl]-3-{4-[bis(2-chloroethyl)Amino]phenyl}-3-aminopropionamide

目的合成N-[3’,3’-双(膦羧基)丙基]-3-{4-[双(2-氯乙基)氨基]苯基}-3-氨基丙酰胺,并进行体外骨靶向性实验。方法以3,3-双(二乙氧膦酰基)-1-硝基丙烷(1)为原料,经氢化还原,再与N-苄氧羰酰异苯丙氨酸氮芥(2)偶联,催化氢化还原得到化合物(4),用溴代三甲基硅烷脱去膦酸酯的烷基得到目标化合物T。用羟磷灰石晶体作为骨模型,测定偶联物T的趋骨性。结果和结论目标物T经1HNMRI、R、MS得到结构确证,体外骨靶向性实验显示,目标物T有良好的骨靶向性。

OBjECtIVE To synthesize N - [ 3＇, 3＇ - di（phosphonoxy） propyl] 3 - / 4 - [ his （2 - chloroethyl） amino ] phenyl } - 3 - aminopropionamide and test its bone targeting characters in vitro.METHODS 3,3 - di（phosphonoxy）propyl - amlno（1） with hydrogenation was conjugated with N- benzyloxcarbonyl Betamerphalan（2）, followed by catalytic hydrogenation for intermediate （4）. Then the title conjugate T was obtained via dealkylation of phospho rate（4） by using trimethysilyl bromide. RESULTS and CONCLUSION The structure of title conju- gate T was verified by ^1H NMR, IR and MS. It showed good bone - seeking ability via hydroxyapatite adhesion tests in vitro.