3-<(3-iodobenzoyl)oxy>-<1R-(exo,exo)>-8-azabicyclo<3.2.1.>octane-2-carboxylic acid methyl ester | 141170-82-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-<(3-iodobenzoyl)oxy>-<1R-(exo,exo)>-8-azabicyclo<3.2.1.>octane-2-carboxylic acid methyl ester
• 英文别名: 3-[(3-iodobenzoyl)oxy]-[1R-(exo,exo)]-8-azabicyclo[3.2.1.]octane-2-carboxylic acid methyl ester；methyl (1R,2R,3S,5S)-3-(3-iodobenzoyl)oxy-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 141170-82-3
• 化学式: C₁₆H₁₈INO₄
• 分子量: 415.228
• InChiKey: GYWKYKFZAGTCMF-RFQIPJPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.13
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.63
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  [11C]methyl iodide 、 3-<(3-iodobenzoyl)oxy>-<1R-(exo,exo)>-8-azabicyclo<3.2.1.>octane-2-carboxylic acid methyl ester 以 二甲基亚砜 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.58h， 生成 methyl (1R,2R,3S,5S)-3-(3-iodobenzoyl)oxy-8-(111C)methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
  参考文献：
  名称：

  Synthesis of carbon-11 labeled iodinated cocaine derivatives and their distribution in baboon brain measured using positron emission tomography

  摘要：

  Three iodine-substituted derivatives of cocaine, methyl esters of 3-[(2'-, 3'-, and 4'-iodobenzoyl)oxy]-8-methyl-[1R-(exo,exo)]-8-azabicyclo [3.2.1]octane-2-carboxylic acid (2a-c), were synthesized and subjected to N-demethylation to give the corresponding noriodococaines 3-[(2'-, 3'-, and 4'-iodobenzoyl)oxy]-[1R-(exo,exo)]-8-azabicyclo[3.2.1]-octane-2-carboxylic acid (3a-c). These were remethylated with [C-11]CH3I to give the [N-C-11-methyl]iodococaines 4a-c which were examined in baboon brain in vivo using positron emission tomography (PET). Compared to [N-C-11]cocaine itself the regional distributions were changed from a highly specific localization in the corpus striatum to more diffuse patterns which included the cerebellum and cortex. Peak brain uptakes and clearance kinetics were also changed. [N-C-11]-o-lodococaine (4a) had a peak uptake in the striatum at 4-5 min after injection of only 17% that of cocaine in the same animal. The peak uptake of [N-C-11]-p-iodococaine (4c) was 60% of that of [N-C-11]cocaine and a clearance half-time of approximately 55 min, twice that of [N-C-11]cocaine. [N-C-11]-m-Iodococaine (4b) displayed half the uptake of [N-C-11]cocaine, buts its clearance was similar to that of the parent molecule. The fractions of unmetabolized tracer in blood plasma at 1-30 min were higher for 4a-c than for [N-C-11]cocaine. Plasma protein binding experiments showed 10%, 0.3%, 1.6%, and 6% as the free fraction for cocaine and o-, m-, and p-iodococaines respectively, consistent with the low brain uptake observed for the ortho isomer, and implicated al-acid glycoprotein as responsible for the low free fraction of o-iodococaine. The potencies of 2a-c to displace tritiated cocaine from striatal membranes were p-iodo almost-equal-to cocaine > m-iodo almost-equal-to o-iodo.

  DOI：

  10.1021/jm00090a005
• 作为产物：
  描述：

  3-iodo-cocaine 在 甲醇 、 1,8-双二甲氨基萘 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 2.5h， 生成 3-<(3-iodobenzoyl)oxy>-<1R-(exo,exo)>-8-azabicyclo<3.2.1.>octane-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis of carbon-11 labeled iodinated cocaine derivatives and their distribution in baboon brain measured using positron emission tomography

  摘要：

  Three iodine-substituted derivatives of cocaine, methyl esters of 3-[(2'-, 3'-, and 4'-iodobenzoyl)oxy]-8-methyl-[1R-(exo,exo)]-8-azabicyclo [3.2.1]octane-2-carboxylic acid (2a-c), were synthesized and subjected to N-demethylation to give the corresponding noriodococaines 3-[(2'-, 3'-, and 4'-iodobenzoyl)oxy]-[1R-(exo,exo)]-8-azabicyclo[3.2.1]-octane-2-carboxylic acid (3a-c). These were remethylated with [C-11]CH3I to give the [N-C-11-methyl]iodococaines 4a-c which were examined in baboon brain in vivo using positron emission tomography (PET). Compared to [N-C-11]cocaine itself the regional distributions were changed from a highly specific localization in the corpus striatum to more diffuse patterns which included the cerebellum and cortex. Peak brain uptakes and clearance kinetics were also changed. [N-C-11]-o-lodococaine (4a) had a peak uptake in the striatum at 4-5 min after injection of only 17% that of cocaine in the same animal. The peak uptake of [N-C-11]-p-iodococaine (4c) was 60% of that of [N-C-11]cocaine and a clearance half-time of approximately 55 min, twice that of [N-C-11]cocaine. [N-C-11]-m-Iodococaine (4b) displayed half the uptake of [N-C-11]cocaine, buts its clearance was similar to that of the parent molecule. The fractions of unmetabolized tracer in blood plasma at 1-30 min were higher for 4a-c than for [N-C-11]cocaine. Plasma protein binding experiments showed 10%, 0.3%, 1.6%, and 6% as the free fraction for cocaine and o-, m-, and p-iodococaines respectively, consistent with the low brain uptake observed for the ortho isomer, and implicated al-acid glycoprotein as responsible for the low free fraction of o-iodococaine. The potencies of 2a-c to displace tritiated cocaine from striatal membranes were p-iodo almost-equal-to cocaine > m-iodo almost-equal-to o-iodo.

  DOI：

  10.1021/jm00090a005