spiro[1,3-dioxane-2,3'-indolin]-2'-one | 113549-13-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: spiro[1,3-dioxane-2,3'-indolin]-2'-one
• 英文别名: Spiro[indoline-3,2'-[1,3]dioxan]-2-one；spiro[1,3-dioxane-2,3'-1H-indole]-2'-one
• CAS: 113549-13-6
• 化学式: C₁₁H₁₁NO₃
• mdl: MFCD00176701
• 分子量: 205.213
• InChiKey: FPCFCMNSACXKRQ-UHFFFAOYSA-N

物化性质

• 熔点：
  150-151 °C(Solv: ethanol (64-17-5))
• 沸点：
  425.0±45.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  spiro[1,3-dioxane-2,3'-indolin]-2'-one 在 羟胺钾盐 、 四丁基溴化铵 、 potassium carbonate 、 potassium iodide 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 7.5h， 生成 N-hydroxy-2-(2'-oxospiro[1,3-dioxane-2,3'-indole]-1'-yl)acetamide
  参考文献：
  名称：

  Novel indoline-2,3-dione derivatives as inhibitors of aminopeptidase N (APN)

  摘要：

  Aminopeptidase N (APN/CD13), as a zinc-containing ectoenzyme, plays a critical role in the process of tumor angiogenesis, invasion and metastasis. Through the docking-based virtual screening of chemical databases and the further activity assay, we discovered that compound 10c exhibits potent and selective inhibitory ability towards APN. In addition, a series of indoline-2,3-dione derivates have been designed and synthesized as APN inhibitors. The results of preliminary activity evaluation showed that compound 12a (IC50 = 0.074 +/- 0.0026 mu M) exhibited the best inhibitory activity against APN, which could be used for further anticancer agent research. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2012.06.024
• 作为产物：
  描述：

  2-羟基亚氨基-n-苯乙酰胺 在 硫酸 、 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 5.5h， 生成 spiro[1,3-dioxane-2,3'-indolin]-2'-one
  参考文献：
  名称：

  Novel indoline-2,3-dione derivatives as inhibitors of aminopeptidase N (APN)

  摘要：

  Aminopeptidase N (APN/CD13), as a zinc-containing ectoenzyme, plays a critical role in the process of tumor angiogenesis, invasion and metastasis. Through the docking-based virtual screening of chemical databases and the further activity assay, we discovered that compound 10c exhibits potent and selective inhibitory ability towards APN. In addition, a series of indoline-2,3-dione derivates have been designed and synthesized as APN inhibitors. The results of preliminary activity evaluation showed that compound 12a (IC50 = 0.074 +/- 0.0026 mu M) exhibited the best inhibitory activity against APN, which could be used for further anticancer agent research. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2012.06.024
• 作为试剂：
  描述：

  2-乙酰氨基-3,4,6-三-O-乙酰-2-脱氧-α-D-吡喃葡萄糖酰基氯 在 苄基三乙基氯化铵 、 potassium carbonate 、 spiro[1,3-dioxane-2,3'-indolin]-2'-one 作用下， 以 氯仿 、 水 为溶剂， 生成 (3aR)-2-甲基-5alpha-(乙酰氧基甲基)-6beta,7alpha-二乙酰氧基-3Aalpha,6,7,7Aalpha-四氢-5H-吡喃并[3,2-d]恶唑
  参考文献：
  名称：

  Synthesis of heteroaromatic N-β-glycosides of N-acetylglucosamine under phase transfer conditions: II. Indolin-2-one glycosaminides

  摘要：

  Regioselective N-beta-glucosamination of various unsubstituted or C4-, C5-, or C6-monosubstituted indolin-2-ones under phase transfer conditions was studied. The regioselectivity was unambiguously proved by H-1 NMR spectroscopy and X-ray analysis. The presence of substituent at C7 of the aromatic ring leads to the formation of either a mixture of isomeric N-beta- and O-beta-D-glucosaminides, or only oxazoline and/or 2-acetamidoglycal irrespective of the reaction conditions.

  DOI：

  10.1134/s1068162008060137

文献信息

• [EN] SUBSTITUTED OXINDOL CB2 AGONISTS FOR PAIN TREATMENT<br/>[FR] AGONISTES DE CB2 DE TYPE OXINDOLE SUBSTITUÉ POUR LE TRAITEMENT DE LA DOULEUR
  申请人：WYETH LLC FORMERLY KNOWN AS WY

  公开号：WO2010077839A1

  公开（公告）日：2010-07-08

  Provided are 3-substituted oxindole derivatives which are agonists of the CB2 receptor, pharmaceutical compositions containing the same, and methods of treatment related to CB2-mediated disorders (e.g., pain, cancer etc.) using the 3-substituted oxindole derivatives and compositions described herein.

  提供了3-取代吲哚衍生物，它们是CB2受体的激动剂，包含相同衍生物的药物组合物，以及使用这些3-取代吲哚衍生物和组合物治疗与CB2介导的疾病（例如疼痛、癌症等）相关的方法。
• [EN] SUBSTITUTED OXINDOLE CB2 AGONISTS<br/>[FR] AGONISTES DE CB2 DE TYPE OXINDOLE SUBSTITUÉ
  申请人：WYETH LLC

  公开号：WO2010090680A1

  公开（公告）日：2010-08-12

  Provided are substituted compounds, or pharmaceutically acceptable salts thereof, wherein: R1 is selected from -(CH2)nRa, -CH(OH)Ra, -CH(ORb)Ra, and -C(O)Ra, or is selected from ORa, SRa, SORa, SO2Ra and NRaRb; R2 and R3 are independently selected from H, halogen, OH, ORa, OWRa, C1-6 alkyl, and WC 1-6 alkyl, wherein C1-6 alkyl or ORa, is optionally substituted with 1, 2, or 3 substitutents independently selected from halogen, CN, OH, ORa, C1-6 alkyl, C1-6 haloalkyl, C3-8cycloalkyl, C6-10 aryl and C4-10 heteroaryl; or R2 and R3, together with the carbon atom to which they are attached, join to form a ring selected from 3-8 membered cycloalkyl, 3-8 membered heterocycloalkyl, C5-C7 oxycycloalkyl, C5.7 dioxycycloalkyl and oxazolidinyl ring, each ring optionally substituted with 1, 2, or 3 substituents independently selected from halogen, CN, OH, 0Ra, C1-6alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, C6-10aryl and C4-10 heteroaryl; R4 is independently selected from H.C1-6 alkyl, C2-6 alkenyl, C2-6alkynyl, C6-10 aryl, C4-10 heteroaryl, -(CH2)n-benzodioxane, -(CH2)n- oxazolidinone and -(CH2)n-C1-6 haloalkyl, each of which is optionally substituted with 1, 2, or 3 substitutents independently selected from halogen, CN, OH, ORa, C1-6 alkyl, C1-6 haloalkyl, C3.8 cycloalkyl, WC3.8 cycloalkyl, C6-10 aryl and C4.10 heteroaryl; which are agonists of the CB2 receptor, pharmaceutical compositions containing the same, and methods of treatment related to CB2-mediated disorders (eg., pain, cancer etc.) using the substituted oxindole compounds and compositions described herein.

  提供的是替代化合物，或其药用盐，其中：R1从-(CH2)nRa，-CH(OH)Ra，-CH(ORb)Ra和-C(O)Ra中选择，或从ORa，SRa，SORa，SO2Ra和NRaRb中选择；R2和R3独立选择自H，卤素，OH，ORa，OWRa，C1-6烷基和WC 1-6烷基，其中C1-6烷基或ORa，可选地取代为1、2或3个取代基，独立选择自卤素，CN，OH，ORa，C1-6烷基，C1-6卤代烷基，C3-8环烷基，C6-10芳基和C4-10杂环芳基；或R2和R3，与它们连接的碳原子一起，结合形成选择自3-8环烷基，3-8杂环烷基，C5-C7氧杂环烷基，C5.7二氧杂环烷基和噁唑烷基的环，每个环可选地取代为1、2或3个取代基，独立选择自卤素，CN，OH，0Ra，C1-6烷基，C1-6卤代烷基，C3-8环烷基，C6-10芳基和C4-10杂环芳基；R4独立选择自H.C1-6烷基，C2-6烯基，C2-6炔基，C6-10芳基，C4-10杂环芳基，-(CH2)n-苯二氧杂环己，-(CH2)n-噁唑烷酮和-(CH2)n-C1-6卤代烷基，每种都可选地取代为1、2或3个取代基，独立选择自卤素，CN，OH，ORa，C1-6烷基，C1-6卤代烷基，C3.8环烷基，WC3.8环烷基，C6-10芳基和C4.10杂环芳基；这些化合物是CB2受体的激动剂，包含它们的药物组合物，以及使用所述的替代氧吲哚化合物和组合物治疗与CB2介导的疾病（例如疼痛、癌症等）相关的方法。
• Potential anticonvulsants. 11. Synthesis and anticonvulsant activity of spiro[1,3-dioxolane-2,3'-indolin]-2'-ones and structural analogs
  作者：Milind Rajopadhye、Frank D. Popp

  DOI：10.1021/jm00400a018

  日期：1988.5

  A number of spiro[1,3-dioxolane-2,3'-indolin]-2'-ones were synthesized and tested for anticonvulsant activity in the maximal electroshock seizure (MES) and pentylenetetrazole seizure threshold (sc-Met) tests. 5'-Chlorospiro[1,3-dioxolane-2,3'-indolin]-2'-one was the most active compound in the MES test and had ED50 = 27.97 mg/kg. Structural analogues spiro[1,3-dioxane-2,3'-indolin]-2'-one, spiro[1,3-dithiolane-2,3'-indolin]-2'-one, spiro[indoline-3,2'-[1,3]-oxathiolan]-2-one, and 3,3-dimethoxyindolin-2-one were also evaluated for anticonvulsant activity. Almost all compounds submitted for screening exhibited the ability to protect mice against electrically and chemically induced seizures. The ED50 and TD50 values for some of the title compounds are reported. Anticonvulsant screenings were carried out through NINCDS, NIH.
• RAJOPADHYE, MILIND;POPP, FRANK D., J. MED. CHEM., 31,(1988) N 5, 1001-1005
  作者：RAJOPADHYE, MILIND、POPP, FRANK D.

  DOI：——

  日期：——
• Novel indoline-2,3-dione derivatives as inhibitors of aminopeptidase N (APN)
  作者：Kang Jin、Xiaopan Zhang、Chunhua Ma、Yingying Xu、Yumei Yuan、Wenfang Xu

  DOI：10.1016/j.bmc.2012.06.024

  日期：2013.5

  Aminopeptidase N (APN/CD13), as a zinc-containing ectoenzyme, plays a critical role in the process of tumor angiogenesis, invasion and metastasis. Through the docking-based virtual screening of chemical databases and the further activity assay, we discovered that compound 10c exhibits potent and selective inhibitory ability towards APN. In addition, a series of indoline-2,3-dione derivates have been designed and synthesized as APN inhibitors. The results of preliminary activity evaluation showed that compound 12a (IC50 = 0.074 +/- 0.0026 mu M) exhibited the best inhibitory activity against APN, which could be used for further anticancer agent research. (C) 2012 Published by Elsevier Ltd.