(R)-2-tert-butoxycarbonyl-7-nitro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid | 215956-90-4

• 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-nitro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• 英文别名: 2-tert-Butoxycarbonyl-7-nitro-1,2,3,4-tetrahydroisoquinoline-(R)-3-carboxylic acid；(3R)-2-[(2-methylpropan-2-yl)oxycarbonyl]-7-nitro-3,4-dihydro-1H-isoquinoline-3-carboxylic acid
• CAS: 215956-90-4
• 化学式: C₁₅H₁₈N₂O₆
• 分子量: 322.318
• InChiKey: DGCRQZUAPWMDGE-GFCCVEGCSA-N

物化性质

• 沸点：
  501.7±50.0 °C(Predicted)
• 密度：
  1.350±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 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：
  113
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-2-tert-butoxycarbonyl-7-nitro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 7.5h， 生成 (R)-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
• 作为产物：
  描述：

  (R)-(+)-1,2,3,4-四氢异喹啉-3-羧酸 在 硫酸 、 potassium nitrate 、 三乙胺 作用下， 以 甲醇 、 水 为溶剂， 生成 (R)-2-tert-butoxycarbonyl-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

• Substituted 6- and 7-aminotetrahydroisoquinolinecarboxylic acids
  申请人：Hoechst Aktiengesellschaft

  公开号：US05962471A1

  公开（公告）日：1999-10-05

  Compounds of the formula I ##STR1## are suitable for the preparation of pharmaceuticals for the prophylaxis and therapy of disorders involving increased activity of matrix-degrading metalloproteinases.

  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。
• 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。
• Synthesis and In Vitro Opioid Receptor Functional Antagonism of Analogues of the Selective Kappa Opioid Receptor Antagonist (3<i>R</i>)-7-Hydroxy-<i>N</i>-((1<i>S</i>)-1-{[(3<i>R</i>,4<i>R</i>)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic)
  作者：Tingwei Bill Cai、Zhou Zou、James B. Thomas、Larry Brieaddy、Hernán A. Navarro、F. Ivy Carroll

  DOI：10.1021/jm701344b

  日期：2008.3.1

  In previous structure-activity relationship (SAR) studies, we identified (3R)-7-hydroxy-N-((1S)-1-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic, 1) as the first potent and selective K opioid receptor antagonist from the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine class of opioid antagonist. In the present study, we report the synthesis and in vitro opioid receptor functional antagonism of a number of analogues of 1 using a [S-35]GTP gamma S binding assay. The results from the studies better define the pharmacophore for this class of K opioid receptor antagonist and has identified new potent and selective kappa antagonist. (3R)-7-Hydroxy-N-[(1 S, 2S)-1-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]methyl}-2-methylbutyl]-1,2,3,4tetrahydroisoquinoline-3-carboxamide (3) with a K-e value of 0.03 nM at the kappa receptor and 100- and 793-fold selectivity relative to the mu and delta receptors was the most potent and selective kappa opioid receptor antagonist identified.
• US5962471A
  申请人：——

  公开号：US5962471A

  公开（公告）日：1999-10-05
• [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.