4-methylene-3,4-dihydro-5H-spiro[furan-2,3'-indoline]-2',5-dione | 1416579-91-3

• 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: 4-methylene-3,4-dihydro-5H-spiro[furan-2,3'-indoline]-2',5-dione
• 英文别名: α-methylene-γ-butyrolactone；3'-methylidenespiro[1H-indole-3,5'-oxolane]-2,2'-dione
• CAS: 1416579-91-3
• 化学式: C₁₂H₉NO₃
• 分子量: 215.208
• InChiKey: VOQFEZBFAQEJMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-methylene-3,4-dihydro-5H-spiro[furan-2,3'-indoline]-2',5-dione 在 5%-palladium/activated carbon 、 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以55%的产率得到4-methyl-3H-spiro[furan-2,3’-indoline]-2’,5(4H)-dion and 4-methyl-3H-spiro[furan-2,3’-indoline]-2’,5(4H)-dione
  参考文献：
  名称：

  靛红衍生的螺环内酯中环外双键的选择性还原†

  摘要：

  我们报告了螺吲哚系统的α-亚甲基-γ-丁内酯基序中环外双键的不寻常面选择性还原。螺-羟吲哚通过金属铟介导的巴比尔型反应组装，然后进行酸催化内酯化。

  DOI：

  10.1039/c2ob27008k
• 作为产物：
  描述：

  methyl 2-((3-hydroxy-2-oxindolin-3-yl)methyl)acrylate 在 对甲苯磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以15%的产率得到4-methylene-3,4-dihydro-5H-spiro[furan-2,3'-indoline]-2',5-dione
  参考文献：
  名称：

  靛红衍生的螺环内酯中环外双键的选择性还原†

  摘要：

  我们报告了螺吲哚系统的α-亚甲基-γ-丁内酯基序中环外双键的不寻常面选择性还原。螺-羟吲哚通过金属铟介导的巴比尔型反应组装，然后进行酸催化内酯化。

  DOI：

  10.1039/c2ob27008k

文献信息

• [EN] SYMBIOTIC PRODRUGS FOR THE TREATMENT OF CANCER AND OTHER DISEASES<br/>[FR] PROMÉDICAMENTS SYMBIOTIQUES POUR LE TRAITEMENT DU CANCER ET D'AUTRES MALADIES
  申请人：UNIV NEBRASKA

  公开号：WO2021188855A1

  公开（公告）日：2021-09-23

  Provided herein are compounds and methods for modulating the NFKB pathway. More particularly, provided are inhibitors of the NFkB pathway and the uses of such inhibitors in regulating diseases and disorders, e.g., to treat cancer, such as ovarian cancer.

  本文提供了用于调节NFKB通路的化合物和方法。更具体地，提供了NFkB通路的抑制剂，以及这些抑制剂在调节疾病和紊乱中的用途，例如用于治疗癌症，如卵巢癌。
• [EN] DIMERS OF COVALENT NFKB INHIBITORS<br/>[FR] DIMÈRES D'INHIBITEURS COVALENTS DE NFĸB
  申请人：UNIV NEBRASKA

  公开号：WO2018119177A1

  公开（公告）日：2018-06-28

  Provided herein are compounds and methods for modulating the NFĸB pathway. More particularly, provided are inhibitors of the NFĸB pathway and the uses of such inhibitors in regulating diseases and disorders, e.g., to treat cancer, autoimmune diseases, inflammatory diseases, diabetes, cardiovascular diseases, or neurological diseases.

  本文提供了调节NFĸB通路的化合物和方法。更具体地，提供了NFĸB通路的抑制剂以及这些抑制剂在调节疾病和疾病中的用途，例如治疗癌症、自身免疫疾病、炎症性疾病、糖尿病、心血管疾病或神经系统疾病。
• 10.3390/molecules29153612
  作者：Mukthapuram, Prathap Reddy、Natarajan, Amarnath

  DOI：10.3390/molecules29153612

  日期：——

  are found in several biologically active molecules. Here, we report nucleophilic domino reactions for the synthesis of α-methylene-γ-butyrolactone/lactam containing spirocyclic oxindoles. The Zn-mediated one-step reaction accommodates a range of substrates and can be used to rapidly generate focused libraries of highly substituted spirocyclic compound.

  在几种生物活性分子中发现了靛红衍生的螺环核心。在这里，我们报道了含有螺环羟吲哚的 α-亚甲基-γ-丁内酯/内酰胺合成的亲核多米诺反应。锌介导的一步反应适用于一系列底物，可用于快速生成高度取代的螺环化合物的集中库。
• Symbiotic prodrugs (SymProDs) dual targeting of NFkappaB and CDK
  作者：Sandeep Rana、Smit Kour、Yogesh A. Sonawane、Caroline M. Robb、Jacob I. Contreras、Smitha Kizhake、Muhammad Zahid、Adam R. Karpf、Amarnath Natarajan

  DOI：10.1111/cbdd.13684

  日期：2020.8

  AbstractThe release of an active drug from the prodrug generates a pro‐fragment that typically has no biological activity and could result in adverse effects. By combining two drugs, wherein each drug acts as a pro‐fragment of the other drug will eliminate the pro‐fragment in the prodrug. As they are prodrugs of each other and are symbiotic, we termed these as symbiotic prodrugs (SymProDs). To test this idea, we generated SymProDs using NFκB inhibitors that contain the reactive α‐methylene‐γ‐butyrolactone moiety and CDK inhibitors with solvent exposed secondary nitrogen atoms. We show that secondary amine prodrugs of α‐methylene‐γ‐butyrolactone containing NFκB inhibitors undergo slow release over a 72 hr period. Using an alkyne‐tagged secondary amine prodrug of α‐methylene‐γ‐butyrolactone containing NFκB inhibitor, we demonstrate target engagement. The NFκB‐CDK SymProDs were ~20‐ to 200‐fold less active against the corresponding CDK inhibitors in in vitro CDK kinase assays. Growth inhibition studies in a panel of ovarian cancer cell lines revealed potency trends of the SymProDs mirrored those of the single treatments suggesting their dissociation in cells. In conclusion, our results suggest that SymProDs offer a productive path forward for advancing compounds with reactive functionality and can be used as dual targeting agents.
• Dimers of Covalent NFKB Inhibitors
  申请人：BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASK

  公开号：US20190322680A1

  公开（公告）日：2019-10-24

  Provided herein are compounds and methods for modulating the NFKB pathway. More particularly, provided are inhibitors of the NFKB pathway and the uses of such inhibitors in regulating diseases and disorders, e.g., to treat cancer, autoimmune diseases, inflammatory diseases, diabetes, cardiovascular diseases, or neurological diseases.