2-(3-(甲亚磺酰基)丙基)异吲哚啉-1,3-二酮 | 98184-57-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 中文名称: 2-(3-(甲亚磺酰基)丙基)异吲哚啉-1,3-二酮
• 英文名称: 2-<(3-Methylsulfinyl)propyl>-1H-isoindole-1,3(2H)-dione
• 英文别名: methyl 3-(N-phthalylamino)propyl sulfoxide；methyl 3-phthalimidopropyl sulfoxide；2-(3-(Methylsulfinyl)propyl)isoindoline-1,3-dione；2-(3-methylsulfinylpropyl)isoindole-1,3-dione
• CAS: 98184-57-7
• 化学式: C₁₂H₁₃NO₃S
• 分子量: 251.306
• InChiKey: QJITYADDXCAAHQ-UHFFFAOYSA-N

物化性质

• 熔点：
  141-142 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  476.0±28.0 °C(Predicted)
• 密度：
  1.375±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  73.7
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2930909090
• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

反应信息

• 作为反应物：
  描述：

  2-(3-(甲亚磺酰基)丙基)异吲哚啉-1,3-二酮 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 methyl 3-aminopropyl sulfoxide
  参考文献：
  名称：

  Synthesis of Novel Analogs of Acetyl Coenzyme A: Mimics of Enzyme Reaction Intermediates

  摘要：

  An improved method for the synthesis of analogs of coenzyme A (CoA) and its thioesters, which are modified in the thiol or thioester moiety, has been developed using a combination of chemical and enzymatic reactions, The enzymes catalyzing the last two steps of CoA biosynthesis were used to prepare a CoA analog (1c) in which an amide bond is replaced by a thioester bond and the thiol group is replaced by a methyl group. Reaction of 1c with a primary amine in aqueous solution results in aminolysis of the thioester linkage to form the desired CoA analog. Reaction with different amines permits the introduction of a variety of functional groups in place of the nor mal thiol or thioester group. This methodology has been used in the synthesis of five new analogs of acetyl-CoA in which the thioester sulfur is replaced by a methylene group and the acetyl group is replaced by carboxylate (14a), nitro (14b), carboxamide (14c), methyl sulfoxide (14d), and methyl sulfone (14e) groups. 14a-c were designed to mimic the possible enolate or enol intermediate in the reaction of citrate synthase and related enzymes. 14a and 14c are potent inhibitors of citrate synthase, with K-i values 1000- and 570-fold lower than the K-m for acetyl-CoA, respectively. CD titrations indicate that 14a and 14c have low affinity for citrate synthase in the absence of oxaloacetate, consistent with their recognition as enol or enolate analogs. 14b is a poor inhibitor of citrate synthase, with affinity slightly lower than that for acetyl-CoA. These results are consistent with generation of the enol form of acetyl-CoA as the nucleophilic intermediate in the reaction of citrate synthase. 14d and 14e were designed to mimic the tetrahedral intermediate or transition state in the reaction of chloramphenicol acetyltransferase and related acetyl-CoA-dependent acetyltransferases. Both compounds are poor inhibitors of chloramphenicol acetyltransferase, with affinities slightly lower than that of acetyl-CoA, indicating that these compounds are not good mimics of the enzyme-bound tetrahedral intermediate or transition state.

  DOI：

  10.1021/ja00090a014
• 作为产物：
  描述：

  2-(3-(甲硫基)丙基)异吲哚啉-1,3-二酮 在 双氧水 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 72.0h， 以100%的产率得到2-(3-(甲亚磺酰基)丙基)异吲哚啉-1,3-二酮
  参考文献：
  名称：

  核苷类似物。14.由三碳链分开的5-氟尿嘧啶和N-（2-氯乙基）-N-亚硝基脲部分的分子组合在小鼠中的抗肿瘤活性的合成。

  摘要：

  将具有N-（2-氯乙基）-N-亚硝基脲基团的两个碳（C2）侧链作为“糖”部分的5-氟尿嘧啶（5-FU）核糖核酸被设计为抗代谢物和烷基化的分子组合但是，游离5-FU的水解释放速度还不够快，不足以显着提高它们对小鼠结肠和乳腺肿瘤表现出的高活性。在目前对反应性更高的C3核糖核苷的合成的研究中，发现通过标准方法可以方便地获得烷氧基/尿嘧啶-1-基类型的烷氧基/尿嘧啶-1-基类型，这些基团连接到前体邻苯二甲酰亚胺的醛中心。 。甲硫基/尿嘧啶-1-基类似物需要相对大量的甲硫醇试剂，对烷基甲基硫醚的α-氯化或其S-氧化物的Pummerer重排，或异硫脲溴化铵的连续水解和甲基化的替代方案的研究令人失望。为了成功制备烷氧基/尿嘧啶-3-基化合物，用于C2同源物的途径需要进行大量的实验修饰。除了这些O，N-和S，N-乙缩醛以外，还制备了带有两个5-F​​U残基的一些N，N-乙缩醛。新药物已经针对小鼠实验性肿瘤

  DOI：

  10.1021/jm9507237

文献信息

• Sato, Yasuhiko; Nakai, Hideo; Wada, Masao, Liebigs Annalen der Chemie, 1985, # 6, p. 1099 - 1118
  作者：Sato, Yasuhiko、Nakai, Hideo、Wada, Masao、Mizoguchi, Tomishige、Hatanaka, Yasumaru、et al.

  DOI：——

  日期：——
• Photochemistry of N-phthaloyl derivatives of methionine
  作者：Axel G. Griesbeck、Harald Mauder、Ingrid Müller、Eva-Maria Peters、Karl Peters、Hans Georg von Schnering

  DOI：10.1016/0040-4039(93)85100-b

  日期：1993.1

  Photodecarboxylation of N-phthaloyl derivatives of methionine sulfoxide 1b and methionine sulfone 1c was observed in acetone as the major reaction. For 1a a fast electron transfer initiated cyclization which leads to the bicyclization product 3 (X-ray structure) was observed in the sensitized photolysis. Direct photolysis of 1a leads preferentially to the tricyclic product 4 and the decarboxylation product 5. The methionine methyl esters 6a-c showed electon transfer initiated cyclization (for 6a) and disproportionation (for 6b), whereas 6c proved to be photostable.
• SATO, YASUHIKO;NAKAI, HIDEO;WADA, MASAO;MIZOGUCHI, TOMISHIGE;HATAMAKA, YA+, LIEBIGS ANN. CHEM., 1985, N 6, 1099-1118
  作者：SATO, YASUHIKO、NAKAI, HIDEO、WADA, MASAO、MIZOGUCHI, TOMISHIGE、HATAMAKA, YA+

  DOI：——

  日期：——
• Synthesis of Novel Analogs of Acetyl Coenzyme A: Mimics of Enzyme Reaction Intermediates
  作者：David P. Martin、Richard T. Bibart、Dale G. Drueckhammer

  DOI：10.1021/ja00090a014

  日期：1994.6

  An improved method for the synthesis of analogs of coenzyme A (CoA) and its thioesters, which are modified in the thiol or thioester moiety, has been developed using a combination of chemical and enzymatic reactions, The enzymes catalyzing the last two steps of CoA biosynthesis were used to prepare a CoA analog (1c) in which an amide bond is replaced by a thioester bond and the thiol group is replaced by a methyl group. Reaction of 1c with a primary amine in aqueous solution results in aminolysis of the thioester linkage to form the desired CoA analog. Reaction with different amines permits the introduction of a variety of functional groups in place of the nor mal thiol or thioester group. This methodology has been used in the synthesis of five new analogs of acetyl-CoA in which the thioester sulfur is replaced by a methylene group and the acetyl group is replaced by carboxylate (14a), nitro (14b), carboxamide (14c), methyl sulfoxide (14d), and methyl sulfone (14e) groups. 14a-c were designed to mimic the possible enolate or enol intermediate in the reaction of citrate synthase and related enzymes. 14a and 14c are potent inhibitors of citrate synthase, with K-i values 1000- and 570-fold lower than the K-m for acetyl-CoA, respectively. CD titrations indicate that 14a and 14c have low affinity for citrate synthase in the absence of oxaloacetate, consistent with their recognition as enol or enolate analogs. 14b is a poor inhibitor of citrate synthase, with affinity slightly lower than that for acetyl-CoA. These results are consistent with generation of the enol form of acetyl-CoA as the nucleophilic intermediate in the reaction of citrate synthase. 14d and 14e were designed to mimic the tetrahedral intermediate or transition state in the reaction of chloramphenicol acetyltransferase and related acetyl-CoA-dependent acetyltransferases. Both compounds are poor inhibitors of chloramphenicol acetyltransferase, with affinities slightly lower than that of acetyl-CoA, indicating that these compounds are not good mimics of the enzyme-bound tetrahedral intermediate or transition state.
• Nucleoside Analogs. 14. The Synthesis and Antitumor Activity in Mice of Molecular Combinations of 5-Fluorouracil and <i>N</i>-(2-Chloroethyl)-<i>N</i>-nitrosourea Moieties Separated by a Three-Carbon Chain
  作者：R. Stanley McElhinney、Joan E. McCormick、Mike C. Bibby、John A. Double、Marco Radacic、Patrick Dumont

  DOI：10.1021/jm9507237

  日期：1996.1.1

  5-fluorouracil (5-FU) seco-nucleosdies having as the "sugar" moiety a two-carbon (C2) side chain carrying a N-(2-chloroethyl)-N-nitrosourea group were designed as molecular combinations of antimetabolite and alkylating agent, but hydrolytic release of free 5-FU was not fast enough for significant contribution to the high activity they showed against colon and breast tumors in mice. In the present study

  将具有N-（2-氯乙基）-N-亚硝基脲基团的两个碳（C2）侧链作为“糖”部分的5-氟尿嘧啶（5-FU）核糖核酸被设计为抗代谢物和烷基化的分子组合但是，游离5-FU的水解释放速度还不够快，不足以显着提高它们对小鼠结肠和乳腺肿瘤表现出的高活性。在目前对反应性更高的C3核糖核苷的合成的研究中，发现通过标准方法可以方便地获得烷氧基/尿嘧啶-1-基类型的烷氧基/尿嘧啶-1-基类型，这些基团连接到前体邻苯二甲酰亚胺的醛中心。 。甲硫基/尿嘧啶-1-基类似物需要相对大量的甲硫醇试剂，对烷基甲基硫醚的α-氯化或其S-氧化物的Pummerer重排，或异硫脲溴化铵的连续水解和甲基化的替代方案的研究令人失望。为了成功制备烷氧基/尿嘧啶-3-基化合物，用于C2同源物的途径需要进行大量的实验修饰。除了这些O，N-和S，N-乙缩醛以外，还制备了带有两个5-F​​U残基的一些N，N-乙缩醛。新药物已经针对小鼠实验性肿瘤