(R)-2-tert-butoxycarbonyl-7-amino-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid | 215956-95-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (R)-2-tert-butoxycarbonyl-7-amino-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• 英文别名: 2-tert-Butoxycarbonyl-7-amino-1,2,3,4-tetrahydroisoquinoline-(R)-3-carboxylic acid；(3R)-7-amino-2-[(2-methylpropan-2-yl)oxycarbonyl]-3,4-dihydro-1H-isoquinoline-3-carboxylic acid
• CAS: 215956-95-9
• 化学式: C₁₅H₂₀N₂O₄
• 分子量: 292.335
• InChiKey: RREQMGDPGYJILI-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-2-tert-butoxycarbonyl-7-amino-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 以 盐酸 为溶剂， 生成 (R)-7-amino-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Substituted 6- and 7-aminotetrahydroisoquinolinecarboxylic acids

  摘要：

  式I ##STR1## 的化合物适用于制备用于预防和治疗涉及基质降解金属蛋白酶活性增加的疾病的药物。

  公开号：

  US05962471A1
• 作为产物：
  描述：

  (R)-(+)-1,2,3,4-四氢异喹啉-3-羧酸 在 palladium on activated charcoal potassium nitrite 、 硫酸 、 氢气 作用下， 以 甲醇 为溶剂， 反应 24.67h， 生成 (R)-2-tert-butoxycarbonyl-7-amino-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Tetrahydroisoquinoline-3-carboxylate based matrix-metalloproteinase inhibitors: design, synthesis and structure–activity relationship

  摘要：

  The design, synthesis and structure-activity relationship (SAR) of a series of nonpeptidic 2-arylsulfonyl-1,2,3,4-tetra-hydro-isoquinoline-3-carboxylates and-hydroxamates as inhibitors of the matrix metalloproteinase human neutrophil collagenase (MMP-8) is described here. Based on available X-ray structures of MMP-8/inhibitor complexes, our structure-based design strategy was directed to complement major protein-ligand interaction regions mainly in the S1' hydrophobic specificity pocket close to the catalytic zinc ion. Here, the rigid 1,2,3,4-tetrahydroisoquinoline scaffold (Tic) provides ideal geometry to combine hydroxamates and carboxylates as typical zinc complexing functionalities, with a broad variety of S1' directed mono- and biaryl substituents consisting of aromatic rings perfectly accommodated within this more hydrophobic region of the MMP-8 inhibitor binding site. The effect of different S1' directed substituents, zinc-complexing groups, chirality and variations of the tetrahydroisoquinoline ring-system is investigated by systematic studies. X-ray structure analyses in combination with 3D-QSAR studies provided an additional understanding of key determinants for MMP-8 affinity in this series. The hypothetical binding mode for a typical molecule as basis for our inhibitor design was found in good agreement with a 1.7 Angstrom X-ray structure of this candidate in complex with the catalytic domain of human MMP-8. After analysis of all systematic variations, 3D-QSAR and X-ray structure analysis, novel S1' directed substituents were designed and synthesized and biologically evaluated. This finally results in inhibitors, which do not only show high biological affinity for MMP-8, but also exhibit good oral bioavailability in several animal species. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00215-8

文献信息

• US5962471A
  申请人：——

  公开号：US5962471A

  公开（公告）日：1999-10-05