[(3S,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}-2-oxopyrrolidin-3-yl]acetic acid | 1244732-97-5

• 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: [(3S,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}-2-oxopyrrolidin-3-yl]acetic acid
• 英文别名: 2-[(3S,5S)-5-[(2S)-2-cyanopyrrolidine-1-carbonyl]-2-oxopyrrolidin-3-yl]acetic acid
• CAS: 1244732-97-5
• 化学式: C₁₂H₁₅N₃O₄
• 分子量: 265.269
• InChiKey: RPSOUHQTWLJGHI-CIUDSAMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(3S,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}-2-oxopyrrolidin-3-yl]acetic acid 、 苯胺 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 2-[(3S,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}-2-oxopyrrolidin-3-yl]-N-phenylacetamide
  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
• 作为产物：
  描述：

  (3S,5S)-3-tert-butoxycarbonylmethyl-5-((2S)-2-cyanopyrrolidine-1-carbonyl)-2-oxopyrrolidine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 1.08h， 生成 [(3S,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}-2-oxopyrrolidin-3-yl]acetic acid
  参考文献：
  名称：

  PYRROLIDINE COMPOUNDS

  摘要：

  以下化合物的化学式：其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、X、Y和Z的定义如本文所述。还公开了一种使用该化合物抑制成纤维细胞激活蛋白的活性或治疗癌症或炎症状况的方法。

  公开号：

  US20100234431A1

文献信息

• Pyrrolidine compounds
  申请人：National Health Research Institutes

  公开号：US08071787B2

  公开（公告）日：2011-12-06

  A compound of the following formula: wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, X, Y, and Z are as defined herein. Also disclosed is a method for inhibiting actively of fibroblast activation protein or for treating cancer or inflammation conditions with such a compound.

  以下为该化合物的公式：其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、X、Y和Z的定义如本文所述。同时还公开了一种使用该化合物抑制成纤维细胞激活蛋白的活性或治疗癌症或炎症病症的方法。
• US8071787B2
  申请人：——

  公开号：US8071787B2

  公开（公告）日：2011-12-06
• 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.
• PYRROLIDINE COMPOUNDS
  申请人：Jiaang Weir-Tong

  公开号：US20100234431A1

  公开（公告）日：2010-09-16

  A compound of the following formula: wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , X, Y, and Z are as defined herein. Also disclosed is a method for inhibiting actively of fibroblast activation protein or for treating cancer or inflammation conditions with such a compound.

  以下化合物的化学式：其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、X、Y和Z的定义如本文所述。还公开了一种使用该化合物抑制成纤维细胞激活蛋白的活性或治疗癌症或炎症状况的方法。