(2S)-1-{(2S,4S)-4-[2-2-(6,7-Dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carbonyl}pyrrolidine-2-carbonitrile | 1243255-07-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-1-{(2S,4S)-4-[2-2-(6,7-Dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carbonyl}pyrrolidine-2-carbonitrile
• 英文别名: (2S)-1-[(2S,4S)-4-[2-(5,7-dihydro-4H-thieno[2,3-c]pyridin-6-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonitrile
• CAS: 1243255-07-3
• 化学式: C₁₉H₂₂N₄O₃S
• 分子量: 386.475
• InChiKey: QTZMSDAPQLNSRC-KKUMJFAQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4,5,6,7-四氢噻吩并[2,3-c]吡啶 、 [(3S,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}-2-oxopyrrolidin-3-yl]acetic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 (2S)-1-{(2S,4S)-4-[2-2-(6,7-Dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carbonyl}pyrrolidine-2-carbonitrile
  参考文献：
  名称：

  Substituted 4-Carboxymethylpyroglutamic Acid Diamides as Potent and Selective Inhibitors of Fibroblast Activation Protein

  摘要：

  Fibroblast activation protein (FAP) belongs to the prolyl peptidase family. FAP inhibition is expected to become a new antitumor target. Most known FAP inhibitors often resemble the dipeptide cleavage products, with a boroproline at the PI site; however, these inhibitors also inhibit DPP-IV, DPP-II, DPP8, and DPP9. Potent and selective FAN inhibitor is needed in evaluating that FA P as a therapeutic target. Therefore, it is important to develop selective FAP inhibitors for the use of target validation, To achieve this, optimization of the nonselective DPP-IV inhibitor 8 led to the discovery of a new class of substituted 4-carboxymethylpyroglutamic acid diamides as FAP inhibitors. SA R studies resulted in a number of FAP inhibitors having IC50 of < 100 nM with excellent selectivity over DPP-IV, DPP-II. DPP8, and DPP9 (IC50 > 100 mu M). Compounds 18a, 18b, and 19 are the only known potent and selective FA P inhibitors, which prompts us to further study the physiological role of FAP.

  DOI：

  10.1021/jm1002556

文献信息

• Substituted 4-Carboxymethylpyroglutamic Acid Diamides as Potent and Selective Inhibitors of Fibroblast Activation Protein
  作者：Ting-Yueh Tsai、Teng-Kuang Yeh、Xin Chen、Tsu Hsu、Yu-Chen Jao、Chih-Hsiang Huang、Jen-Shin Song、Yu-Chen Huang、Chia-Hui Chien、Jing-Huai Chiu、Shih-Chieh Yen、Hung-Kuan Tang、Yu-Sheng Chao、Weir-Torn Jiaang

  DOI：10.1021/jm1002556

  日期：2010.9.23

  Fibroblast activation protein (FAP) belongs to the prolyl peptidase family. FAP inhibition is expected to become a new antitumor target. Most known FAP inhibitors often resemble the dipeptide cleavage products, with a boroproline at the PI site; however, these inhibitors also inhibit DPP-IV, DPP-II, DPP8, and DPP9. Potent and selective FAN inhibitor is needed in evaluating that FA P as a therapeutic target. Therefore, it is important to develop selective FAP inhibitors for the use of target validation, To achieve this, optimization of the nonselective DPP-IV inhibitor 8 led to the discovery of a new class of substituted 4-carboxymethylpyroglutamic acid diamides as FAP inhibitors. SA R studies resulted in a number of FAP inhibitors having IC50 of < 100 nM with excellent selectivity over DPP-IV, DPP-II. DPP8, and DPP9 (IC50 > 100 mu M). Compounds 18a, 18b, and 19 are the only known potent and selective FA P inhibitors, which prompts us to further study the physiological role of FAP.