摘要
羟甲芬太尼（Ｉ）是一个新的高强度高选择性阿片μ受体激动剂。本文用ｃｉｓ－Ａ－Ｎ－［１－（２－羟基－２－苯乙基）－３－甲基－４－哌啶基］－苯胺（ＩＩ）或ｃｉｓ－Ｎ－［１－（苯甲酰甲基）－３－甲基－４－哌啶基］－苯胺（ＩＩＩ）作为前体合成了［１１Ｃ］－羟甲芬太尼，以便用正电子发射断层扫描（ＰＥＴ）来观察μ受体。通过水解ｃｉｓ－Ａ－羟甲芬太尼（Ｉ）和ｃｉｓ－Ｎ－［１－（苯甲酰甲基）－３－甲基－４－哌啶］－Ｎ－苯基丙酰胺（ｃｉｓ－ＩＶ）的４－Ｎ－丙酰基分别获得ＩＩ和ＩＩＩ。溴乙烷的格氏试剂与回旋加速器产生的［１１Ｃ］－二氧化碳反应后继而直接加入邻苯二甲酸二酰氯和２，６－二叔丁基吡啶生成同位素标记中间体［１１Ｃ］－丙酰氯。［１１Ｃ］－丙酰氯与ＯＨ－前体（ＩＩ）反应后再经ＨＰＬＣ分离纯化直接得［１１Ｃ］－羟甲芬太尼；［１１Ｃ］－丙酰氯与酮－前体（ＩＩＩ）反应后，再用硼氢化钠甲醇溶液处理，然后进行ＨＰＬＣ分离纯化得［１１Ｃ］－羟甲芬太尼。两种方法均可获得ｌｌ．１～１４．８ＧＢｑ／μｍｏｌ的特异性放射化学纯［１１Ｃ］－羟甲芬太尼。总共耗时为４０～５０ｍｉｎ（ＥＯＢ）。
Ohmefentanyl I
is a new,highly potent and selective agonist for opiate μ-recptor.
In order to visualize the μ-receptor by Positron Emission
Tomography(PET),I labelcd with carbon- 11 was synthesized using
OH-precursor II or keto-precursor III.The OH-precursor Il was
obtained by hydrolysis of cis-A-ohmefentanyl in 6 mol/L hydrochloric
acid and the keto-precursor III was prepared by hydrolysis of cis-IV
in 8 mol/L hydrochloric acid.The active intermediate[11C]-propionyl
chloride was prepared by the reaction between Grignard reagent
ethylmagnesium bromide and cyclotron-produced[11C]-carbon
dioxide,followed by direct treatment of the radio-complex with
phthaloyldichloride and 2,6-di-t-butylpyridine. Reaction of the
OH-precursor Il with[11C]-propionyl chlorideorreaction of the
keto-precursor IIl with[11C]-propionyl chloride and treatment with
sodiumborohydride followed by HPLC separation all
afforded[11C]-ohmefentanyl with high specific activityof ll.1～14.8
GBq/μmol(300～400 mCi/μmo1)at 45～50 minutes after the end of
bombardment(EOB).
出处
《药学学报》
CAS
CSCD
北大核心
1994年第11期823-828,共6页
Acta Pharmaceutica Sinica
关键词
羟甲芬太尼
芬太尼衍生物
阿片
受体
合成
Ohmefentanyl, Fentanyl derivative, Opiate
receptor,[11C]-Labeled propionylchloride ,[11C]-Ohmefentanyl
