(R)-7-nitro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid | 215956-89-1

• 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)-7-nitro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• 英文别名: (r)-7-Nitro-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid；(3R)-7-nitro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• CAS: 215956-89-1
• 化学式: C₁₀H₁₀N₂O₄
• 分子量: 222.2
• InChiKey: DUNHNFQEXKIPND-SECBINFHSA-N

物化性质

• 沸点：
  454.1±45.0 °C(Predicted)
• 密度：
  1.420±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  95.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-7-nitro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  1,2,3,4-Tetrahydroisoquinolinyl sulfamic acids as phosphatase PTP1B inhibitors

  摘要：

  High-throughput screening of the P&GP corporate repository against several protein tyrosine phosphatases identified the sulfamic acid moiety as potential phosphotyrosine mimetic. Incorporation of the sulfamic acid onto a 1,2,3,4-tetrahydroisoquinoline scaffold provided a promising starting point for PTP1B inhibitor design. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.051
• 作为产物：
  描述：

  (R)-(+)-1,2,3,4-四氢异喹啉-3-羧酸 在 硫酸 、 potassium nitrate 作用下， 生成 (R)-7-nitro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
  参考文献：
  名称：

  1,2,3,4-Tetrahydroisoquinolinyl sulfamic acids as phosphatase PTP1B inhibitors

  摘要：

  High-throughput screening of the P&GP corporate repository against several protein tyrosine phosphatases identified the sulfamic acid moiety as potential phosphotyrosine mimetic. Incorporation of the sulfamic acid onto a 1,2,3,4-tetrahydroisoquinoline scaffold provided a promising starting point for PTP1B inhibitor design. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.051

文献信息

• Tetrahydroisoquinolnyl sulfamic acids
  申请人：Klopfenstein Rees Sean

  公开号：US20050154011A1

  公开（公告）日：2005-07-14

  Compounds of formula (I): are effective in the treatment of protein tyrosine phosphatase (PTPase) mediated disorder such as diabetes.

  公式（I）的化合物在治疗蛋白酪氨酸磷酸酶（PTPase）介导的疾病，如糖尿病方面具有有效性。
• Tetrahydroisoquinoline-3-carboxylate based matrix-metalloproteinase inhibitors: design, synthesis and structure–activity relationship
  作者：Hans Matter、Manfred Schudok、Wilfried Schwab、Werner Thorwart、Denis Barbier、Günter Billen、Burkhard Haase、Bernhard Neises、Klaus-Ulrich Weithmann、Theo Wollmann

  DOI：10.1016/s0968-0896(02)00215-8

  日期：2002.11

  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.
• Discovery of a novel 2,3,11,11a-tetrahydro-1H-pyrazino[1,2-b]isoquinoline-1,4(6H)-dione series promoting neurogenesis of human neural progenitor cells
  作者：Hong Lin、Haiyan Fang、Jamie Wang、Qinghua Meng、Xuedong Dai、Sharon Wu、Jie Luo、Dan Pu、Libo Chen、Douglas Minick、Ken Arai、Emiri T. Mandeville、Eng Lo、Julie C. Holder、Tsu Tshen Chuang、Jing Zhao

  DOI：10.1016/j.bmcl.2015.05.084

  日期：2015.9

  A novel neurogenic compound (1), discovered from a mouse neural progenitor cell (NPC) screen, showed profound neurogenic effect on human NPCs. Synthesis and SAR of this novel 2,3,11,11a-tetrahydro-1H-pyrazino[ 1,2-b]isoquinoline-1,4(6H)-dione series are described. Compound 20 is brain penetrable in rodents, and promotes neurogenesis in wild type mice, therefore it is a good tool molecule to study neurogenesis induction as a potential treatment for conditions associated with neurogenesis impairment diseases. (C) 2015 Elsevier Ltd. All rights reserved.
• [EN] TETRAHYDROISOQUINOLINYL SULFAMIC ACIDS<br/>[FR] ACIDES SULFAMIQUES DE TETRAHYDROISOQUINOLINYLE
  申请人：PROCTER & GAMBLE

  公开号：WO2004074256A1

  公开（公告）日：2004-09-02

  Compounds of formula (I): (I)are effective in the treatment of protein tyrosine phosphatase (PTPase) mediated disorder such as diabetes.
• 1,2,3,4-Tetrahydroisoquinolinyl sulfamic acids as phosphatase PTP1B inhibitors
  作者：Sean R. Klopfenstein、Artem G. Evdokimov、Anny-Odile Colson、Neil T. Fairweather、Jeffrey J. Neuman、Matthew B. Maier、Jeffrey L. Gray、Gina S. Gerwe、George E. Stake、Brian W. Howard、Julie A. Farmer、Matthew E. Pokross、Thomas R. Downs、Bhavani Kasibhatla、Kevin G. Peters

  DOI：10.1016/j.bmcl.2005.12.051

  日期：2006.3

  High-throughput screening of the P&GP corporate repository against several protein tyrosine phosphatases identified the sulfamic acid moiety as potential phosphotyrosine mimetic. Incorporation of the sulfamic acid onto a 1,2,3,4-tetrahydroisoquinoline scaffold provided a promising starting point for PTP1B inhibitor design. (C) 2006 Elsevier Ltd. All rights reserved.