(3R)-N-(4-biphenylylsulfonyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid | 191326-92-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3R)-N-(4-biphenylylsulfonyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid
• 英文别名: 2-(Biphenyl-4-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid；(3R)-2-(4-phenylphenyl)sulfonyl-3,4-dihydro-1H-isoquinoline-3-carboxylic acid
• CAS: 191326-92-8
• 化学式: C₂₂H₁₉NO₄S
• 分子量: 393.463
• InChiKey: BNVMUDXGABBWGP-OAQYLSRUSA-N

物化性质

• 沸点：
  628.5±65.0 °C(Predicted)
• 密度：
  1.346±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R)-N-(4-biphenylylsulfonyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid 在 dimethyl sulfide borane 、 2-碘酰基苯甲酸 作用下， 生成 (Z)-1-(2-([1,1'-biphenyl]-4-ylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)-N-methylmethanimine oxide
  参考文献：
  名称：

  Relative Configuration and Conformation of Key In- termediates for Matrix Metalloproteinase Inhibitors as Determined by NMR-Based Restrained Simulated Annealing and Validated by X-ray Analysis

  摘要：

  DOI：

  10.1021/ja982415e
• 作为产物：
  描述：

  对联苯磺酰氯 、 (R)-(+)-1,2,3,4-四氢异喹啉-3-羧酸 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 (3R)-N-(4-biphenylylsulfonyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic 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

• S type 2-substituted hydroxy-2-indolidinylbutyric ester compounds and
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US05932732A1

  公开（公告）日：1999-08-03

  A process for preparing S type 2-substituted hydroxy-2-indolidinyl-butyric ester compound \x9bII!: ##STR1## wherein R.sup.o is residue of nitrogen-containing fused heterocyclic carboxylic acid having absolute configuration of "R"(in which the nitrogen atom is protected), R.sup.1 and R.sup.2 are lower alkyl group, and E is ester residue, which is useful as an intermediate for preparing camptothecin derivatives having antitumor activities, which comprises 2-ethylating 2-substituted hydroxy-2-indolidinylacetic ester compound \x9bI!: ##STR2## wherein the symbols are as defined above.

  一种制备S型2-取代羟基-2-吲哚丁酸酯化合物的方法\x9bII!：##STR1##其中R.sup.o是氮杂环羧酸的残基，具有“R”的绝对构型（其中氮原子被保护），R.sup.1和R.sup.2是较低的烷基基团，E是酯基团，可用作制备具有抗肿瘤活性的紫杉醇衍生物的中间体，包括对2-取代羟基-2-吲哚丁酸乙酯化合物进行乙酰化的步骤\x9bI!：##STR2##其中符号如上定义。
• S type 2-substituted hydroxy-2-indolidinylbutyric ester compounds and process for preparation thereof
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：US20030135049A1

  公开（公告）日：2003-07-17

  A process for preparing S type 2-substituted hydroxy-2-indolidinylbutyric ester compound [II]: 1 wherein R o is residue of nitrogen-containing fused heterocyclic carboxylic acid having absolute configuration of “R” (in which the nitrogen atom is protected), R1 and R2 are lower alkyl groups, and E is ester residue, which is useful as an intermediate for preparing camptothecin derivatives having antitumor activities, which comprises 2-ethylating 2-substituted hydroxy-2-indolidinylacetic ester compound [I]: 2 wherein the symbols are as defined above.

  一种制备S型2-取代羟基-2-吲哚丁酸酯化合物II的方法：其中Ro是氮杂环羧酸残基，具有“R”的绝对构型（其中氮原子受保护），R1和R2是较低的烷基基团，E是酯残基，该化合物是制备具有抗肿瘤活性的喜树碱衍生物的中间体，包括对2-取代羟基-2-吲哚丁酸乙酯化合物I进行2-乙基化，其中符号如上所定义。
• Stype 2-substituted hydroxy-2-indolidinylbutyric ester compounds and process for preparation thereof
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US20020161231A1

  公开（公告）日：2002-10-31

  A process for preparing S type 2-substituted hydroxy-2-indolidinylbutyric ester compound [II]: 1 wherein R o is residue of nitrogen-containing fused heterocyclic carboxylic acid having absolute configuration of “R” (in which the nitrogen atom is protected), R1 and R2 are lower alkyl groups, and E is ester residue, which is useful as an intermediate for preparing camptothecin derivatives having antitumor activities, which comprises 2-ethylating 2-substituted hydroxy-2-indolidinylacetic ester compound [I]: 2 wherein the symbols are as defined above.

  一种制备S型2-取代羟基-2-吲哚丁酸酯化合物II的方法：其中Ro是氮杂环羧酸残基，具有“R”的绝对构型（其中氮原子受保护），R1和R2是低烷基基团，E是酯基残基，可用作制备具有抗肿瘤活性的喜树碱衍生物的中间体，该方法包括对2-取代羟基-2-吲哚乙酸酯化合物I进行2-乙基化，其中符号如上所定义。
• Nitrogen-containing fused heterocyclic carboxylic acids having an absolute configuration of “R”
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US07060832B2

  公开（公告）日：2006-06-13

  Nitrogen-containing fused heterocyclic carboxylic acid having an absolute configuration of “R” of the formula [XIX]: wherein Y is substituted or unsubstituted arylsulfonyl group or an alkylsulfonyl group, and n is 0 or 1, or a salt thereof.

  具有绝对构型“R”的含氮融合杂环羧酸的化学式[XIX]，其中Y是取代或未取代的芳基磺酰基或烷基磺酰基，n为0或1，或其盐。
• S type 2-substituted hydroxy-2-indolidinylbutyric ester compounds as intermediates for camptothecin derivatives
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：EP0845464A2

  公开（公告）日：1998-06-03

  A process for preparing S type 2-substituted hydroxy-2-indolidinyl-butyric ester compound [II]: wherein R° is residue of nitrogen-containing fused heterocyclic carboxylic acid having absolute configuration of "R"(in which the nitrogen atom is protected), R1 and R2 are lower alkyl group, and E is ester residue, which is useful as an intermediate for preparing camptothecin derivatives having antitumor activities,    comprises 2-ethylating 2-substituted hydroxy-2-indolidinylacetic ester compound [I]: wherein the symbols are as defined above.

  一种制备 S 型 2-取代羟基-2-吲哚烷基丁酸酯化合物的工艺[II]： 其中 R°为绝对构型为 "R"（其中氮原子被保护）的含氮融合杂环羧酸残基，R1 和 R2 为低级烷基，E 为酯残基，可用作制备具有抗肿瘤活性的喜树碱衍生物的中间体、 包括 2-乙基化 2-取代羟基-2-吲哚乙酸酯化合物[I]： 其中符号如上定义。