3',6'-二(乙酰氧基)-5,6-二氨基-螺[异苯并呋喃-1(3H),9'-[9H]氧杂蒽]-3-酮 | 205391-02-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 3',6'-二(乙酰氧基)-5,6-二氨基-螺[异苯并呋喃-1(3H),9'-[9H]氧杂蒽]-3-酮
• 中文别名: 4,5-二氨基荧光素二乙酸酯
• 英文名称: 4,5-diaminofluorescein diacetate
• 英文别名: 4,5-diaminofIuorescein diacetate；DAF-2 DA；(6'-acetyloxy-5,6-diamino-3-oxospiro[2-benzofuran-1,9'-xanthene]-3'-yl) acetate
• CAS: 205391-02-2
• 化学式: C₂₄H₁₈N₂O₇
• 分子量: 446.416
• InChiKey: PTSUYDXEEKDBQU-UHFFFAOYSA-N

物化性质

• 沸点：
  719.0±60.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Predicted)
• 闪点：
  87 °C
• 溶解度：
  二甲基亚砜：<2mg/毫升

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  140
• 氢给体数：
  2
• 氢受体数：
  9

安全信息

• WGK Germany：
  3
• 安全说明：
  S26
• 危险类别码：
  R36/38

制备方法与用途

生物活性

DAF-2DA（5,6-二氨基荧光素二乙酯）是测量NO最广泛使用的一种荧光探针。

体外研究

硝酸氧化合物是一种自由基信号分子。多种方法可用于测量NO，其中荧光探针对NO定位的测量方法非常普遍。4,5-二氨基荧光素二乙酯（DAF-2DA）是应用最为广泛的NO探针。该方法基于将4,5-二氨基荧光素二乙酯（DAF-2DA）施用于细胞，一旦被细胞摄取并进入胞质后，细胞内的酯酶会裂解酰基团生成4,5-二氨基荧光素（DAF-2）。生成的DAF-2可以迅速与NO的氧化产物N₂O₃反应，生成高度荧光的DAF-2T（三唑荧光素）。

反应信息

• 作为产物：
  描述：

  6-Amino-3',6'-dihydroxy-5-nitrospiro[2-benzofuran-3,9'-xanthene]-1-one 在 sodium sulfide 、 sodium hydrogensulfide 、 caesium carbonate 作用下， 以 水 、 乙腈 为溶剂， 生成 3',6'-二(乙酰氧基)-5,6-二氨基-螺[异苯并呋喃-1(3H),9'-[9H]氧杂蒽]-3-酮
  参考文献：
  名称：

  Development of a Fluorescent Indicator for Nitric Oxide Based on the Fluorescein Chromophore.

  摘要：

  内源性一氧化氮（NO）似乎可以调节许多生理和病理生理过程。为了获得一氧化氮在体内功能的直接证据，我们开发了 4，5-二氨基荧光素（DAF-2）作为一氧化氮的新型荧光指示剂。由 NO 和 DAF-2 反应生成的绿色荧光三唑荧光素对 NO 具有高灵敏度（检测限：5 nM）。将膜渗透性 DAF-2 二乙酸酯（DAF-2DA）装入活化的大鼠主动脉平滑肌细胞中，细胞内的酯键被酯酶水解，生成 DAF-2。细胞内的荧光增加与 NO 浓度有关。这种成像方法可用于在分子水平上研究 NO 的动态生物作用，并具有较高的时间和空间分辨率。

  DOI：

  10.1248/cpb.46.373

文献信息

• Development of a Fluorescent Indicator for Nitric Oxide Based on the Fluorescein Chromophore.
  作者：Hirotatsu KOJIMA、Kuniko SAKURAI、Kazuya KIKUCHI、Shigenori KAWAHARA、Yutaka KIRINO、Hiroshi NAGOSHI、Yasunobu HIRATA、Tetsuo NAGANO

  DOI：10.1248/cpb.46.373

  日期：——

  Endogenous nitric oxide (NO) appears to modulate many physiological and pathophysiolgoical processes. In order to obtain direct evidence for NO functions in vivo, we have developed 4, 5-diaminofluorescein (DAF-2) as a novel fluorescent indicator for NO. Green-fluorescent triazolofluorescein formed by the reaction of NO and DAF-2 affords high sensitivity for NO (detection limit : 5 nM). Membrane-permeable DAF-2 diacetate (DAF-2DA) was loaded into activated rat aortic smooth muscle cells, where the ester bonds are hydrolyzed by intracellular esterase, generating DAF-2. The fluorescence in the cells increased in a NO concentration-dependent manner. This imaging method should be useful for studies of the dynamic biological actions of NO at the molecular level with fine temporal and spatial resolution.

  内源性一氧化氮（NO）似乎可以调节许多生理和病理生理过程。为了获得一氧化氮在体内功能的直接证据，我们开发了 4，5-二氨基荧光素（DAF-2）作为一氧化氮的新型荧光指示剂。由 NO 和 DAF-2 反应生成的绿色荧光三唑荧光素对 NO 具有高灵敏度（检测限：5 nM）。将膜渗透性 DAF-2 二乙酸酯（DAF-2DA）装入活化的大鼠主动脉平滑肌细胞中，细胞内的酯键被酯酶水解，生成 DAF-2。细胞内的荧光增加与 NO 浓度有关。这种成像方法可用于在分子水平上研究 NO 的动态生物作用，并具有较高的时间和空间分辨率。
• Diaminofluorescein derivative
  申请人：Nagano; Tetsuo

  公开号：US05874590A1

  公开（公告）日：1999-02-23

  A compound useful for the measurement of nitrogen monoxide under a substantially neutral condition which is represented by the following formula (I): ##STR1## wherein R.sup.1 and R.sup.2 represent amino groups that substitute at adjacent positions on the phenyl ring; R.sup.3 and R.sup.4 independently represent a hydrogen atom or an acyl group; R.sup.5, R.sup.6, R.sup.7, and R.sup.8 independently represent a hydrogen atom, a C.sub.1-6 alkyl group, allyl group, or a halogen atom.

  一种在基本中性条件下用于测量一氧化氮的化合物，其化学式为(I)：##STR1## 其中，R.sup.1和R.sup.2代表取代苯环上相邻位置的氨基基团；R.sup.3和R.sup.4独立地代表氢原子或酰基基团；R.sup.5、R.sup.6、R.sup.7和R.sup.8独立地代表氢原子、C.sub.1-6烷基、烯丙基或卤素原子。
• A GNRH ANTAGONIST FOR USE IN THE TREATMENT OF A WOMEN AFFECTED WITH POLYCYSTIC OVARY SYNDROME
  申请人：Institut National de la Santé et de la Recherche Médicale

  公开号：EP3600373A1

  公开（公告）日：2020-02-05
• [EN] A GNRH ANTAGONIST FOR USE IN THE TREATMENT OF A WOMEN AFFECTED WITH POLYCYSTIC OVARY SYNDROME<br/>[FR] ANTAGONISTE DE LA GNRH DESTINÉ À ÊTRE UTILISÉ DANS LE TRAITEMENT D'UNE FEMME AFFECTÉE PAR LE SYNDROME DES OVAIRES POLYKYSTIQUES
  申请人：INST NAT SANTE RECH MED

  公开号：WO2018177746A1

  公开（公告）日：2018-10-04

  The present invention relates to the field of therapeutic treatment of polycystic ovary syndrome (PCOS). Polycystic ovary syndrome, PCOS, is the most common female reproductive disorder against which no therapeutic solution is available, beyond changes in the lifestyle. The inventors have now shown by using in vivo preclinical models, that individuals affected with PCOS have an abnormal elevated production of GnRH and that this elevated production of GnRH was transmitted to their offspring that also develop PCOS. Further, by examining AMH levels in a cohort of pregnant PCOS and control women, the inventors have found that AMH concentrations are significantly higher in PCOS women as compared to healthy women during the second trimester of gestation. These unexpected findings has allowed conceiving both prevention and treatment therapeutic strategies based on the administration of GnRH antagonists. Especially, the present invention relates to a gonadotropin-releasing hormone (GnRH) antagonist for its use in a woman affected with polycystic ovary syndrome (PCOS) for preventing the occurrence of PCOS in the offspring of the said woman. Even more interestingly, the present invention relates to a gonadotropin-releasing hormone (GnRH) antagonist for its use to rescue ovulation and fertility in postpuberal PCOS affected individuals.
• Detection and Imaging of Nitric Oxide with Novel Fluorescent Indicators:  Diaminofluoresceins
  作者：Hirotatsu Kojima、Naoki Nakatsubo、Kazuya Kikuchi、Shigenori Kawahara、Yutaka Kirino、Hiroshi Nagoshi、Yasunobu Hirata、Tetsuo Nagano

  DOI：10.1021/ac9801723

  日期：1998.7.1

  Nitric oxide is a gaseous, free radical which plays a role as an intracellular second messenger and a diffusable intercellular messenger. To obtain direct evidence for NO functions in vivo, we have designed and synthesized diaminofluoresceins (DAFs) as novel fluorescent indicators for NO. The fluorescent chemical transformation of DAFs is based on the reactivity of the aromatic vicinal diamines with NO in the presence of dioxygen. The N-nitrosation of DAFs, yielding the highly green-fluorescent triazole form, offers the advantages of specificity, sensitivity, and a simple protocol for the direct detection of NO (detection limit 5 nM). The fluorescence quantum efficiencies are increased more than 100 times after the transformation of DAFs by NO. Fluorescence detection with visible light excitation and high sensitivity enabled the practical assay of NO production in living cells. Membrane-permeable DAF-2 diacetate (DAF-2 DA) can be used for real-time bioimaging of NO with fine temporal and spatial resolution. The dye was loaded into activated rat aortic smooth muscle cells, where the ester bonds are hydrolyzed by intracellular esterase, generating DAF-2. The fluorescence in the cells increased in a NO concentration-dependent manner.

  一氧化氮是一种气态自由基，它既是细胞内的第二信使，也是可扩散的细胞间信使。为了直接证明一氧化氮在体内的功能，我们设计并合成了二氨基荧光素（DAFs），作为一氧化氮的新型荧光指示剂。DAFs 的荧光化学变化是基于芳香族环状二胺在二氧存在下与 NO 的反应性。DAFs 的 N-亚硝基化反应生成了高绿色荧光的三唑形式，具有特异性、灵敏度高、操作简单等优点，可直接检测 NO（检测限为 5 nM）。DAF 被 NO 转化后，荧光量子效率提高了 100 多倍。利用可见光激发的荧光检测和高灵敏度，可以对活细胞中的 NO 生成进行实际检测。膜渗透性 DAF-2 diacetate（DAF-2 DA）可用于对 NO 进行实时生物成像，并具有较高的时间和空间分辨率。将染料装入活化的大鼠主动脉平滑肌细胞，细胞内酯酶水解酯键，生成 DAF-2。细胞内的荧光增加与 NO 浓度有关。