N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-[(1,1-dimethylethoxy)carbonyl]-2-piperazineacetamide | 212650-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-[(1,1-dimethylethoxy)carbonyl]-2-piperazineacetamide
• 英文别名: Tert-butyl 3-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-4-(2-imidazol-1-ylpyrimidin-4-yl)piperazine-1-carboxylate
• CAS: 212650-42-5
• 化学式: C₂₆H₃₁N₇O₅
• 分子量: 521.576
• InChiKey: YEEVPZKKNDWLAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-[(1,1-dimethylethoxy)carbonyl]-2-piperazineacetamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-N-[(1,3-benzodioxol-5-yl)methyl]piperazine-2-acetamide
  参考文献：
  名称：

  [EN] NOVEL IN-VIVO PROBE FOR REAL TIME LONGITUDINAL MONITORING OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN LIVING CELLS AND ANIMALS
  [FR] NOUVELLE SONDE IN VIVO POUR LA SURVEILLANCE LONGITUDINALE EN TEMPS RÉEL DE L'OXYDE NITRIQUE SYNTHASE INDUCTIBLE DANS DES CELLULES VIVANTES ET DES ANIMAUX VIVANTS

  摘要：

  本公开涉及一种由式I化合物表示的体内荧光或放射性探针，该探针能够在实时基础上对诱导型一氧化氮合酶（iNOS）在活细胞和活体动物中的表达进行纵向成像。本公开的探针可以具有对iNOS酶的特异性和高亲和力结合，并且降低了酶的抑制性质，还能够在同一实验对象的生理或疾病过程的进展中纵向监测iNOS的表达以及其活性或一氧化氮（NO）的产生，而无需使用单独的对照和实验对象。本公开还提供了一种快速、廉价的实时方法，用于准确、方便和可逆地在活细胞和活体动物中可视化iNOS的表达和活性，同时还能在活体生理环境中同时成像其催化产物一氧化氮（NO）。

  公开号：

  WO2018092034A1
• 作为产物：
  描述：

  N-4-BOC-2-哌嗪乙酸甲酯 在 lithium hydroxide monohydrate 、 potassium carbonate 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 72.5h， 生成 N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-[(1,1-dimethylethoxy)carbonyl]-2-piperazineacetamide
  参考文献：
  名称：

  [EN] NOVEL IN-VIVO PROBE FOR REAL TIME LONGITUDINAL MONITORING OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN LIVING CELLS AND ANIMALS
  [FR] NOUVELLE SONDE IN VIVO POUR LA SURVEILLANCE LONGITUDINALE EN TEMPS RÉEL DE L'OXYDE NITRIQUE SYNTHASE INDUCTIBLE DANS DES CELLULES VIVANTES ET DES ANIMAUX VIVANTS

  摘要：

  本公开涉及一种由式I化合物表示的体内荧光或放射性探针，该探针能够在实时基础上对诱导型一氧化氮合酶（iNOS）在活细胞和活体动物中的表达进行纵向成像。本公开的探针可以具有对iNOS酶的特异性和高亲和力结合，并且降低了酶的抑制性质，还能够在同一实验对象的生理或疾病过程的进展中纵向监测iNOS的表达以及其活性或一氧化氮（NO）的产生，而无需使用单独的对照和实验对象。本公开还提供了一种快速、廉价的实时方法，用于准确、方便和可逆地在活细胞和活体动物中可视化iNOS的表达和活性，同时还能在活体生理环境中同时成像其催化产物一氧化氮（NO）。

  公开号：

  WO2018092034A1

文献信息

• [EN] NOVEL IN-VIVO PROBE FOR REAL TIME LONGITUDINAL MONITORING OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN LIVING CELLS AND ANIMALS<br/>[FR] NOUVELLE SONDE IN VIVO POUR LA SURVEILLANCE LONGITUDINALE EN TEMPS RÉEL DE L'OXYDE NITRIQUE SYNTHASE INDUCTIBLE DANS DES CELLULES VIVANTES ET DES ANIMAUX VIVANTS
  申请人：PANDA KOUSTUBH

  公开号：WO2018092034A1

  公开（公告）日：2018-05-24

  The present disclosure relates to an in vivo fluorescent or radioactive probe represented by a compound of formula I which is capable of longitudinal imaging of inducible nitric oxide synthase (iNOS) expression in living cells and living animals on a real time basis. The probe of the present disclosure can exhibit specific and high affinity binding to the iNOS enzyme with reduced enzyme inhibitory property and also enables longitudinal monitoring of iNOS expression along with its activity or NO production in a same experimental subject throughout the progression of a physiological or disease process without employing separate subjects as controls and experimental. The present disclosure further provides a rapid and inexpensive real time method for visualizing iNOS expression and its activity in living cells and living animals precisely, conveniently and reversibly along with simultaneous in vivo imaging of its catalytic product, nitric oxide (NO) in live physiological settings.

  本公开涉及一种由式I化合物表示的体内荧光或放射性探针，该探针能够在实时基础上对诱导型一氧化氮合酶（iNOS）在活细胞和活体动物中的表达进行纵向成像。本公开的探针可以具有对iNOS酶的特异性和高亲和力结合，并且降低了酶的抑制性质，还能够在同一实验对象的生理或疾病过程的进展中纵向监测iNOS的表达以及其活性或一氧化氮（NO）的产生，而无需使用单独的对照和实验对象。本公开还提供了一种快速、廉价的实时方法，用于准确、方便和可逆地在活细胞和活体动物中可视化iNOS的表达和活性，同时还能在活体生理环境中同时成像其催化产物一氧化氮（NO）。
• NOVEL IN-VIVO PROBE FOR REAL TIME LONGITUDINAL MONITORING OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN LIVING CELLS AND ANIMALS
  申请人：Panda Koustubh

  公开号：US20190309169A1

  公开（公告）日：2019-10-10

  The present disclosure relates to an in vivo fluorescent or radioactive probe represented by a compound of formula I which is capable of longitudinal imaging of inducible nitric oxide synthase (iNOS) expression in living cells and living animals on a real time basis. The probe of the present disclosure can exhibit specific and high affinity binding to the iNOS enzyme with reduced enzyme inhibitory property and also enables longitudinal monitoring of iNOS expression along with its activity or NO production in a same experimental subject throughout the progression of a physiological or disease process without employing separate subjects as controls and experimental. The present disclosure further provides a rapid and inexpensive real time method for visualizing iNOS expression and its activity in living cells and living animals precisely, conveniently and reversibly along with simultaneous in vivo imaging of its catalytic product, nitric oxide (NO) in live physiological settings.
• Design, Synthesis, and Activity of 2-Imidazol-1-ylpyrimidine Derived Inducible Nitric Oxide Synthase Dimerization Inhibitors
  作者：David D. Davey、Marc Adler、Damian Arnaiz、Keith Eagen、Shawn Erickson、William Guilford、Margaret Kenrick、Michael M. Morrissey、Mike Ohlmeyer、Gonghua Pan、Vidyadhar M. Paradkar、John Parkinson、Mark Polokoff、Kurt Saionz、Cecile Santos、Babu Subramanyam、Ron Vergona、Robert G. Wei、Marc Whitlow、Bin Ye、Zuchun (Spring) Zhao、James J. Devlin、Gary Phillips

  DOI：10.1021/jm061319i

  日期：2007.3.1

  By the screening of a combinatorial library for inhibitors of nitric oxide (NO) formation by the inducible isoform of nitric oxide synthase (iNOS) using a whole-cell assay, 2-(imidazol-1-yl)pyrimidines were identified. Compounds were found to inhibit the dimerization of iNOS monomers, thus preventing the formation of the dimeric, active form of the enzyme. Optimization led to the selection of the potent, selective, and orally available iNOS dimerization inhibitor, 21b, which significantly ameliorated adjuvant-induced arthritis in a rat model. Analysis of the crystal structure of the 21b-iNOS monomer complex provided a rationalization for both the SAR and the mechanism by which 21b blocks the formation of the protein-protein interaction present in the dimeric form of iNOS.