异补骨脂素酰胺类化合物的合成及其AKR1C3抑制活性  

Synthesis and AKR1C3 Inhibitory Activity of Angelicin Amides

作　　者：孙明娜 江晓怡[1,2] 曾思莹 黄萍 郑雪花 刘欢[1,2] 张超 SUN Ming-na;JIANG Xiao-yi;ZENG Si-ying;HUANG Ping;ZHENG Xue-hua;LIU Huan;ZHANG Chao(Key Laboratory of Molecular Target&Clinical Pharmacology and the State Key Laboratory of Respiratory Disease,School of Pharmaceutical Sciences,Guangzhou Medical University,Guangzhou 511436,China;The Fifth Affiliated Hospital,Guangzhou Medical University,Guangzhou 511436,China)

机构地区：[1]广州医科大学药学院广东省分子靶标&临床药理学重点实验室与呼吸疾病国家重点实验室,广东广州511436 [2]广州医科大学附属第五医院,广东广州511436

出　　处：《化学试剂》2023年第4期160-166,共7页Chemical Reagents

基　　金：广东省中医药局科研项目(20222121);广州医科大学十四五高峰学科建设项目(06-410-2107218);广州医科大学学科建设项目-药学拔尖人才培养本科生项目(02-410-2206299,02-445-2301196XM);广州医科大学2022年一流专业建设项目-大学生科研创新能力提升项目(02-408-2203-2029)。

摘　　要：以7-羟基香豆素为初始原料,经Duff甲酰化反应、Rap-Stoermer反应、水解反应和缩合反应得具有酰胺侧链的角型呋喃香豆素(异补骨脂素)类化合物;利用HR-MS、1HNMR及13 CNMR确证化合物的结构;通过中通量抑酶活性测试方法评价化合物对AKR1C3及AKR1C1的抑制作用。合成了7个新的异补骨脂素酰胺类化合物;初步酶活性测试结果显示,N,N-二正丙基-4-甲基-2-氧-2 H-呋喃并[2,3-h]色烯-8-甲酰胺对AKR1C3具有一定的选择性抑制作用。采用上述方法可成功合成异补骨脂素酰胺类化合物,化合物5e具有一定的选择性AKR1C3抑制作用,可为后续研究提供一定的依据。This study is aiming at the synthesis of angelicin amides and evaluation of their inhibitory effect on AKR1C3.Methods are listed as followed:the angular furocoumarin(angelicin)compounds with amide side chain were prepared using 7-hydroxycoumarins as the initial materials through Duff formylation,Rap-Stoermer reaction,hydrolysis,and condensation in sequence.The structures of the compounds were confirmed by combining HR-MS,1HNMR and 13 CNMR characterizations.The medium flux enzyme activity inhibition tests were carried out to evaluate the inhibition of the compounds on AKR1C3 and AKR1C1.Seven new angelicin amides were synthesized and confirmed.According to the preliminary enzyme activity results,4-methyl-2-oxo-N,N-dipropyl-2 H-furo[2,3-h]chromene-8-carboxamide showed a certain selective inhibition effect on AKR1C3.The angelicin amides can be successfully synthesized by the method described above.Compound 5e exhibits a certain selective inhibitory effect on AKR1C3,which can provide some basis for subsequent research.

关 键 词：异补骨脂素 酰胺 AKR1C3 呋喃香豆素 合成 

分 类 号：R91[医药卫生—药学]