(3R)-N-benzyloxy-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide | 362477-34-7

• 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: (3R)-N-benzyloxy-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
• 英文别名: (3R)-N-benzyloxy-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinole-3-carboxamide；tert-butyl (3R)-3-(phenylmethoxycarbamoyl)-3,4-dihydro-1H-isoquinoline-2-carboxylate
• CAS: 362477-34-7
• 化学式: C₂₂H₂₆N₂O₄
• 分子量: 382.459
• InChiKey: VTVRRZQUSTVKLU-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R)-N-benzyloxy-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide 在 吡啶 、 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 3.25h， 生成 ((R)-3-Benzyloxycarbamoyl-3,4-dihydro-1H-isoquinolin-2-yl)-(4-methoxy-phenyl)-phosphinic acid butyl ester
  参考文献：
  名称：

  New Type of Metalloproteinase Inhibitor:  Design and Synthesis of New Phosphonamide-Based Hydroxamic Acids

  摘要：

  A series of phosphonamide-based hydroxamate derivatives were synthesized, and the inhibitory activities were evaluated against various metalloproteinases in order to clarify its selectivity profile. Among the four diastereomeric isomers resulting from the chirality at the C-3 and P atoms, the compound with a (R,R)-configuration both at the C-3 position and the phosphorus atom was found to be potently active, while the other diastereomeric isomers were almost inactive. A number of (R,R)-compounds synthesized here exhibited broad spectrum activities with nanomolar K-i values against MMP-1, -3, -9, and TACE and also showed nanomolar IC50 values against HB-EGF shedding in a cell-based inhibition assay. The modeling study using X-ray structure of MMP-3 suggested the possible binding mode of the phosphonamide-based inhibitors.

  DOI：

  10.1021/jm0103211
• 作为产物：
  描述：

  D-1,2,3,4-四氢异喹啉-3-羧酸盐酸盐 在 sodium carbonate 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 (3R)-N-benzyloxy-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
  参考文献：
  名称：

  New Type of Metalloproteinase Inhibitor:  Design and Synthesis of New Phosphonamide-Based Hydroxamic Acids

  摘要：

  A series of phosphonamide-based hydroxamate derivatives were synthesized, and the inhibitory activities were evaluated against various metalloproteinases in order to clarify its selectivity profile. Among the four diastereomeric isomers resulting from the chirality at the C-3 and P atoms, the compound with a (R,R)-configuration both at the C-3 position and the phosphorus atom was found to be potently active, while the other diastereomeric isomers were almost inactive. A number of (R,R)-compounds synthesized here exhibited broad spectrum activities with nanomolar K-i values against MMP-1, -3, -9, and TACE and also showed nanomolar IC50 values against HB-EGF shedding in a cell-based inhibition assay. The modeling study using X-ray structure of MMP-3 suggested the possible binding mode of the phosphonamide-based inhibitors.

  DOI：

  10.1021/jm0103211

文献信息

• New Strategy for Antedrug Application:  Development of Metalloproteinase Inhibitors as Antipsoriatic Drugs
  作者：Masaaki Sawa、Takako Tsukamoto、Takao Kiyoi、Kiriko Kurokawa、Fumio Nakajima、Yuichiro Nakada、Koichi Yokota、Yoshimasa Inoue、Hirosato Kondo、Kohichiro Yoshino

  DOI：10.1021/jm010349c

  日期：2002.2.1

  Phosphonamide-based inhibitors were synthesized and evaluated for the inhibitory activities against the shedding of epidermal growth factors, amphiregulin and lieparin-binding EGF-like growth factor, that would participate in the development of psoriasis. All compounds exhibited excellent inhibitory activities for these EGF sheddings; however, they also inhibited matrix metalloproteinases (MMPs). To avoid adverse effects reported by the clinical development of MMP inhibitors, the antedrug concept was introduced. Among the phosphonamide inhibitors, the 2,2,2-trifluoroethyl ester 8d and 2,2-difluoroethyl ester 8c showed rapid decomposition in human plasma, which is an essential property for the antedrug. Topical applications of these compounds significantly suppressed TPA-induced epidermal hyperplasia in murin skin, a model of psoriasis. These results suggested that the phosphonamide-based inhibitors have a therapeutic potential for the treatment of psoriasis as an antedrug application.
• New Type of Metalloproteinase Inhibitor:  Design and Synthesis of New Phosphonamide-Based Hydroxamic Acids
  作者：Masaaki Sawa、Takao Kiyoi、Kiriko Kurokawa、Hiroshi Kumihara、Minoru Yamamoto、Tomohiro Miyasaka、Yasuko Ito、Ryoichi Hirayama、Tomomi Inoue、Yasuyuki Kirii、Eiji Nishiwaki、Hiroshi Ohmoto、Yu Maeda、Etsuko Ishibushi、Yoshimasa Inoue、Kohichiro Yoshino、Hirosato Kondo

  DOI：10.1021/jm0103211

  日期：2002.2.1

  A series of phosphonamide-based hydroxamate derivatives were synthesized, and the inhibitory activities were evaluated against various metalloproteinases in order to clarify its selectivity profile. Among the four diastereomeric isomers resulting from the chirality at the C-3 and P atoms, the compound with a (R,R)-configuration both at the C-3 position and the phosphorus atom was found to be potently active, while the other diastereomeric isomers were almost inactive. A number of (R,R)-compounds synthesized here exhibited broad spectrum activities with nanomolar K-i values against MMP-1, -3, -9, and TACE and also showed nanomolar IC50 values against HB-EGF shedding in a cell-based inhibition assay. The modeling study using X-ray structure of MMP-3 suggested the possible binding mode of the phosphonamide-based inhibitors.