5-(4-(3-[18F]fluoropropyl)-4-methyl-2-thioxo-2,4-dihydro-1H-benzo[d][1,3]oxazin-6-yl)-1H-pyrrole-2-carbonitrile | 1229520-88-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 5-(4-(3-[18F]fluoropropyl)-4-methyl-2-thioxo-2,4-dihydro-1H-benzo[d][1,3]oxazin-6-yl)-1H-pyrrole-2-carbonitrile
• 英文别名: [18F]FPTP；4-[18F]fluoropropyl-tanaproget；5-[4-(3-(18F)fluoranylpropyl)-4-methyl-2-sulfanylidene-1H-3,1-benzoxazin-6-yl]-1H-pyrrole-2-carbonitrile
• CAS: 1229520-88-0
• 化学式: C₁₇H₁₆FN₃OS
• 分子量: 328.4
• InChiKey: WFTKAYFSQWLZBZ-SQZVAGKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(4-allyl-4-methyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-5-cyano-pyrrole-1-carboxylic acid tert-butyl ester 在 劳森试剂 、 硼烷四氢呋喃络合物 、 [18F]-tetrabutylammonium fluoride 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 2-甲基-2-丁醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 6.67h， 生成 5-(4-(3-[18F]fluoropropyl)-4-methyl-2-thioxo-2,4-dihydro-1H-benzo[d][1,3]oxazin-6-yl)-1H-pyrrole-2-carbonitrile
  参考文献：
  名称：

  Development of [F-18]Fluorine-Substituted Tanaproget as a Progesterone Receptor Imaging Agent for Positron Emission Tomography

  摘要：

  The level of progesterone receptors (PRs) in breast tumors can be used to guide the selection of endocrine therapies for breast cancer patients. To this end, we have prepared a fluorine-18 labeled analogue of Tanaproget, a nonsteroidal progestin with very high PR binding affinity and low affinity for androgen and glucocorticoid receptors, and have studied its tissue distribution in estrogen-primed rats to evaluate its potential for imaging PR levels by positron emission tomography. 4-[F-18]Fluoropropyl-Tanaproget ([F-18], FPTP) was prepared in three steps, within 140 min at an overall decay-corrected yield of 5% and effective specific activity of >550 Ci/mmol. In biodistribution studies, [F-18]9 uptake was high in target tissues at both 1 and 3 h (uterus, 4.55 and 5.26%ID/g; ovary, 2.32 and 2.20%ID/g, respectively) and was cleanly blocked by coinjection of excess unlabeled compound. Uterus to blood and muscle activity ratios were 9.2 and 5.2 at 1 h and 32 and 26 at 3 h, respectively. The biodistribution of [F-18]9 compares favorably to that of previously prepared F-18 labeled steroidal progestins, FENP and FFNP. Its high target tissue uptake efficiency and selectivity, and prolonged retention, suggest that it has excellent promise as a PET imaging agent for PR-positive breast tumors.

  DOI：

  10.1021/bc1001054

文献信息

• Development of [F-18]Fluorine-Substituted Tanaproget as a Progesterone Receptor Imaging Agent for Positron Emission Tomography
  作者：Jae Hak Lee、Hai-bing Zhou、Carmen S. Dence、Kathryn E. Carlson、Michael J. Welch、John A. Katzenellenbogen

  DOI：10.1021/bc1001054

  日期：2010.6.16

  The level of progesterone receptors (PRs) in breast tumors can be used to guide the selection of endocrine therapies for breast cancer patients. To this end, we have prepared a fluorine-18 labeled analogue of Tanaproget, a nonsteroidal progestin with very high PR binding affinity and low affinity for androgen and glucocorticoid receptors, and have studied its tissue distribution in estrogen-primed rats to evaluate its potential for imaging PR levels by positron emission tomography. 4-[F-18]Fluoropropyl-Tanaproget ([F-18], FPTP) was prepared in three steps, within 140 min at an overall decay-corrected yield of 5% and effective specific activity of >550 Ci/mmol. In biodistribution studies, [F-18]9 uptake was high in target tissues at both 1 and 3 h (uterus, 4.55 and 5.26%ID/g; ovary, 2.32 and 2.20%ID/g, respectively) and was cleanly blocked by coinjection of excess unlabeled compound. Uterus to blood and muscle activity ratios were 9.2 and 5.2 at 1 h and 32 and 26 at 3 h, respectively. The biodistribution of [F-18]9 compares favorably to that of previously prepared F-18 labeled steroidal progestins, FENP and FFNP. Its high target tissue uptake efficiency and selectivity, and prolonged retention, suggest that it has excellent promise as a PET imaging agent for PR-positive breast tumors.