3-formyl-10-(1-methylethyl)-10H-phenothiazine | 182961-54-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 3-formyl-10-(1-methylethyl)-10H-phenothiazine
• 英文别名: 10-Propan-2-ylphenothiazine-3-carbaldehyde
• CAS: 182961-54-2
• 化学式: C₁₆H₁₅NOS
• 分子量: 269.367
• InChiKey: CWGAAXLPENRIRD-UHFFFAOYSA-N

物化性质

• 沸点：
  435.1±44.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-formyl-10-(1-methylethyl)-10H-phenothiazine 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 以100%的产率得到3-hydroxymethyl-10-(1-methylethyl)-10H-phenothiazine
  参考文献：
  名称：

  结合吩噻嗪部分作为角鲨烯合酶抑制剂的奎尼丁衍生物的合成和生物学评估。

  摘要：

  角鲨烯合酶抑制剂有可能成为优良的降胆固醇药。为了研究其结构对抑制仓鼠肝微粒体酶的影响，合成了一系列结合吩噻嗪系统的奎尼丁衍生物。（+/-）-3-（10-甲基-10H-吩噻嗪-3-基甲氧基）奎尼丁盐酸盐（19）是该系列中最有效的抑制剂，IC（50）值为0.12 microM。口服给予仓鼠化合物19可有效降低血浆总胆固醇水平和血浆甘油三酸酯水平。化合物19显示出降低血浆转氨酶水平的趋势，这是肝毒性的指标。发现对映体纯的（-）-19，YM-53546比相应的（+）-对映体更有效。

  DOI：

  10.1248/cpb.52.1204
• 作为产物：
  描述：

  吩噻嗪 在 sodium hydride 、 三氯氧磷 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.0h， 生成 3-formyl-10-(1-methylethyl)-10H-phenothiazine
  参考文献：
  名称：

  Unraveling Polymorphism Dependent Cytotoxicity, Cellular Uptake, and Live Cell Imaging Using Luminescent Polymorphs

  摘要：

  Polymorphism‐dependent cytotoxicity and cellular uptake of drug molecules have been studied for the past two decades. However, visualizing the polymorph‐dependent cellular uptake and cytotoxicity using microscopy imaging technique has not been reported yet. The luminescent polymorph is an ideal candidate to validate the above hypothesis. Herein, we report the polymorph‐dependent cellular uptake, cytotoxicity, and bio‐imaging functions of polymorphs 1Y and 1R of a naphthalimide‐phenothiazine dyad. These polymorphs show different luminescence colors in the solid state and exhibit aggregation‐induced enhanced emission (AIEE) in the DMSO‐Water mixture. Bioimaging, cytotoxicity assay, and fluorescence‐activated cell sorting (FACS) studies revealed that these polymorphs show different levels of cytotoxicity, cellular uptake, localization, and imaging potential. Detailed photophysical, morphological, and biological studies revealed that the difference in molecular conformation in these polymorphs enables them to form aggregates of different sizes and morphology, which leads to the differential uptake of these into the cells and consequently shows different cytotoxicity and imaging potentials.

  DOI：

  10.1002/chem.202400868

文献信息

• NOVEL QUINUCLIDINE DERIVATIVES HAVING TRICYCLIC FUSED HETERO RING
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP0812840A1

  公开（公告）日：1997-12-17

  A quinuclidine derivative represented by the following general formula (I), a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof, which has strong squalene synthase inhibiting activity and is useful as a cholesterol lowering agent without causing side effects. (Symbols in the formula represent the following meanings; R1: a hydrogen atom, a halogen atom or a lower alkyl group, R2: a hydrogen atom, a hydroxyl group or a lower alkoxy group, : a single bond or a double bond, with the proviso that R2 does not exist when is a double bond, X and Y: the same or different from each other and each represents a bond, an oxygen atom (-O-), a carbonyl group (-CO-), a group represented by the formula -S(O)p- or a group represented by the formula -NR3-, p: 0, 1 or 2, R3: a hydrogen atom or a lower alkyl group which may have a substituent, A: a saturated or unsaturated lower alkylene group, a group of the formula -(CH2)mZ(CH2)n- or a group of the formula -(CH2)mZ(CH2)nCR4=, Z: an oxygen atom (-O-), a group of the formula -S(O)q-, a carbonyl group (-CO-) or a group of the formula -NR5-, R4: a hydrogen atom, a halogen atom or a lower alkyl group, R5: a hydrogen atom or a lower alkyl group, m and n: the same or different from each other and each is 0 or an integer of 1 to 5, m + n: an integer of 1 to 5 q: 0, 1 or 2, with the proviso that, when either one of X and Y is a bond, A is a group represented by the formula -(CH2)mZ(CH2)nCR4=.)

  一种由以下通式（I）代表的喹烯酮衍生物、其药学上可接受的盐、其水合物或其溶液，该衍生物具有很强的角鲨烯合成酶抑制活性，可用作降低胆固醇的药物，且不会产生副作用。 (式中符号代表以下含义； R1：氢原子、卤素原子或低级烷基、 R2：氢原子、羟基或低级烷氧基、 R2：单键或双键，但 R2 为双键时不存在、 X和Y：彼此相同或不同，各自代表一个键、一个氧原子（-O-）、一个羰基（-CO-）、一个由式-S(O)p-代表的基团或一个由式-NR3-代表的基团、 p:0、1 或 2、 R3：氢原子或可带有取代基的低级烷基、 A：饱和或不饱和低级亚烷基、式-(CH2)mZ(CH2)n-或式-(CH2)mZ(CH2)nCR4=的基团、 Z：氧原子（-O-）、式-S(O)q-的基团、羰基（-CO-）或式-NR5-的基团、 R4：氢原子、卤素原子或低级烷基、 R5：氢原子或低级烷基、 m 和 n：相同或互不相同，各自为 0 或 1 至 5 的整数、 m+n：1 至 5 的整数 q：0、1 或 2、 但条件是，当 X 和 Y 中任何一个是键时，A 是由式-(CH2)mZ(CH2)nCR4=代表的基团。）
• US5830902A
  申请人：——

  公开号：US5830902A

  公开（公告）日：1998-11-03
• Synthesis and Biological Evaluation of Quinuclidine Derivatives Incorporating Phenothiazine Moieties as Squalene Synthase Inhibitors
  作者：Tsukasa Ishihara、Hirotoshi Kakuta、Hiroshi Moritani、Tohru Ugawa、Isao Yanagisawa

  DOI：10.1248/cpb.52.1204

  日期：——

  superior hypocholesterolemic agents. A series of quinuclidine derivatives incorporating phenothiazine systems was synthesized in order to investigate the effects of their structure on the inhibition of hamster liver microsomal enzyme. (+/-)-3-(10-Methyl-10H-phenothiazin-3-ylmethoxy)quinuclidine hydrochloride (19) was the most potent inhibitor in this series with an IC(50) value of 0.12 microM. Oral dosing

  角鲨烯合酶抑制剂有可能成为优良的降胆固醇药。为了研究其结构对抑制仓鼠肝微粒体酶的影响，合成了一系列结合吩噻嗪系统的奎尼丁衍生物。（+/-）-3-（10-甲基-10H-吩噻嗪-3-基甲氧基）奎尼丁盐酸盐（19）是该系列中最有效的抑制剂，IC（50）值为0.12 microM。口服给予仓鼠化合物19可有效降低血浆总胆固醇水平和血浆甘油三酸酯水平。化合物19显示出降低血浆转氨酶水平的趋势，这是肝毒性的指标。发现对映体纯的（-）-19，YM-53546比相应的（+）-对映体更有效。
• Unraveling Polymorphism Dependent Cytotoxicity, Cellular Uptake, and Live Cell Imaging Using Luminescent Polymorphs
  作者：Akkarakkaran Thayyil Muhammed Munthasir、Poonam Rani、Pandi Dhanalakshmi、Sambit Pradhan、Pakkirisamy Thilagar

  DOI：10.1002/chem.202400868

  日期：——

  Polymorphism‐dependent cytotoxicity and cellular uptake of drug molecules have been studied for the past two decades. However, visualizing the polymorph‐dependent cellular uptake and cytotoxicity using microscopy imaging technique has not been reported yet. The luminescent polymorph is an ideal candidate to validate the above hypothesis. Herein, we report the polymorph‐dependent cellular uptake, cytotoxicity, and bio‐imaging functions of polymorphs 1Y and 1R of a naphthalimide‐phenothiazine dyad. These polymorphs show different luminescence colors in the solid state and exhibit aggregation‐induced enhanced emission (AIEE) in the DMSO‐Water mixture. Bioimaging, cytotoxicity assay, and fluorescence‐activated cell sorting (FACS) studies revealed that these polymorphs show different levels of cytotoxicity, cellular uptake, localization, and imaging potential. Detailed photophysical, morphological, and biological studies revealed that the difference in molecular conformation in these polymorphs enables them to form aggregates of different sizes and morphology, which leads to the differential uptake of these into the cells and consequently shows different cytotoxicity and imaging potentials.