(R)-3-(1H-indol-3-yl)-2-(4-nitrobenzenesulfonylamino)propionic acid methyl ester | 203639-62-7

• 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: (R)-3-(1H-indol-3-yl)-2-(4-nitrobenzenesulfonylamino)propionic acid methyl ester
• 英文别名: methyl (2R)-3-(1H-indol-3-yl)-2-[(4-nitrophenyl)sulfonylamino]propanoate
• CAS: 203639-62-7
• 化学式: C₁₈H₁₇N₃O₆S
• 分子量: 403.415
• InChiKey: WGDBBDXIWYQDST-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  143
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-3-(1H-indol-3-yl)-2-(4-nitrobenzenesulfonylamino)propionic acid methyl ester 在 N-甲基吗啉 、 palladium 10% on activated carbon 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 22.67h， 生成 (R)-2-[4-(4-fluorobenzoylamino)benzenesulfonylamino]-3-(1H-indol-3-yl)propionic acid
  参考文献：
  名称：

  Design, Synthesis, and Initial Evaluation of a High Affinity Positron Emission Tomography Probe for Imaging Matrix Metalloproteinases 2 and 9

  摘要：

  The activity of matrix metalloproteinases (MMPs) is elevated locally under many pathological conditions. Gelatinases MMP2 and MMP9 are of particular interest because of their implication in angiogenesis, cancer cell proliferation and metastasis, and atherosclerotic plaque rupture. The aim of this study was to identify and develop a selective gelatinase inhibitor for imaging active MMP2/MMP9 in vivo. We synthesized a series of N-sulfonylamino acid derivatives with low to high nanomolar inhibitory potencies. (R)-2-(4-(4-Fluorobenzamido)phenylsulfonamido)-3-(1H-indol-3-yl)propanoic acid (7) exhibited the best in vitro binding properties: MMP2 IC50 = 1.8 nM, MMP9 IC50 = 7.2 nM. Radiolabeling of 7 with no carrier added F-18-radioisotope was accomplished starting from iodonium salts as precursors. The radiochemical yield strongly depended on the iodonium counteranion (ClO4- > Br- > TFA(-) > tosylate). F-18-7 was obtained in up to 20% radiochemical yield (decay corrected), high radiochemical purity, and >90 GBq/mu mol specific radioactivity. The radiolabeled compound showed excellent stability in vitro and in mice in vivo.

  DOI：

  10.1021/jm400156p
• 作为产物：
  描述：

  D-色氨酸甲酯盐酸盐 、 对硝基苯磺酰氯 在 N-甲基吗啉 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以83%的产率得到(R)-3-(1H-indol-3-yl)-2-(4-nitrobenzenesulfonylamino)propionic acid methyl ester
  参考文献：
  名称：

  Design, Synthesis, and Initial Evaluation of a High Affinity Positron Emission Tomography Probe for Imaging Matrix Metalloproteinases 2 and 9

  摘要：

  The activity of matrix metalloproteinases (MMPs) is elevated locally under many pathological conditions. Gelatinases MMP2 and MMP9 are of particular interest because of their implication in angiogenesis, cancer cell proliferation and metastasis, and atherosclerotic plaque rupture. The aim of this study was to identify and develop a selective gelatinase inhibitor for imaging active MMP2/MMP9 in vivo. We synthesized a series of N-sulfonylamino acid derivatives with low to high nanomolar inhibitory potencies. (R)-2-(4-(4-Fluorobenzamido)phenylsulfonamido)-3-(1H-indol-3-yl)propanoic acid (7) exhibited the best in vitro binding properties: MMP2 IC50 = 1.8 nM, MMP9 IC50 = 7.2 nM. Radiolabeling of 7 with no carrier added F-18-radioisotope was accomplished starting from iodonium salts as precursors. The radiochemical yield strongly depended on the iodonium counteranion (ClO4- > Br- > TFA(-) > tosylate). F-18-7 was obtained in up to 20% radiochemical yield (decay corrected), high radiochemical purity, and >90 GBq/mu mol specific radioactivity. The radiolabeled compound showed excellent stability in vitro and in mice in vivo.

  DOI：

  10.1021/jm400156p

文献信息

• Highly Selective and Orally Active Inhibitors of Type IV Collagenase (MMP-9 and MMP-2):  <i>N</i>-Sulfonylamino Acid Derivatives
  作者：Yoshinori Tamura、Fumihiko Watanabe、Takuji Nakatani、Ken Yasui、Masahiro Fuji、Tadafumi Komurasaki、Hiroshige Tsuzuki、Ryuji Maekawa、Takayuki Yoshioka、Kenji Kawada、Kenji Sugita、Mitsuaki Ohtani

  DOI：10.1021/jm9707582

  日期：1998.2.1

  Various N-sulfonylamino acid derivatives were synthesized and evaluated for their in vitro and in vivo activities to inhibit type IV collagenase (MMP-9 and MMP-2). When the amino acid residue and the sulfonamide moiety were modified, their inhibitory activities were greatly affected by the structure of the sulfonamide moiety. A series of aryl sulfonamide derivatives containing biaryl, tetrazole, amide, and triple bond were found to be potent and highly selective inhibitors of MMP-9 and MMP-2 In addition, these compounds were orally active in animal models of tumor growth and metastasis. These results revealed the potential of the N-sulfonylamino acid derivatives as a new type of candidate drug for the treatment of cancer.
• Design, Synthesis, and Initial Evaluation of a High Affinity Positron Emission Tomography Probe for Imaging Matrix Metalloproteinases <b>2</b> and <b>9</b>
  作者：Svetlana V. Selivanova、Timo Stellfeld、Tobias K. Heinrich、Adrienne Müller、Stefanie D. Krämer、P. August Schubiger、Roger Schibli、Simon M. Ametamey、Bernhard Vos、Jörg Meding、Marcus Bauser、Joachim Hütter、Ludger M. Dinkelborg

  DOI：10.1021/jm400156p

  日期：2013.6.27

  The activity of matrix metalloproteinases (MMPs) is elevated locally under many pathological conditions. Gelatinases MMP2 and MMP9 are of particular interest because of their implication in angiogenesis, cancer cell proliferation and metastasis, and atherosclerotic plaque rupture. The aim of this study was to identify and develop a selective gelatinase inhibitor for imaging active MMP2/MMP9 in vivo. We synthesized a series of N-sulfonylamino acid derivatives with low to high nanomolar inhibitory potencies. (R)-2-(4-(4-Fluorobenzamido)phenylsulfonamido)-3-(1H-indol-3-yl)propanoic acid (7) exhibited the best in vitro binding properties: MMP2 IC50 = 1.8 nM, MMP9 IC50 = 7.2 nM. Radiolabeling of 7 with no carrier added F-18-radioisotope was accomplished starting from iodonium salts as precursors. The radiochemical yield strongly depended on the iodonium counteranion (ClO4- > Br- > TFA(-) > tosylate). F-18-7 was obtained in up to 20% radiochemical yield (decay corrected), high radiochemical purity, and >90 GBq/mu mol specific radioactivity. The radiolabeled compound showed excellent stability in vitro and in mice in vivo.