4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide | 1314805-66-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 英文名称: 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide
• 英文别名: 4-Cyclopropyl-7-(3-methoxyphenoxy)-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide；4-cyclopropyl-7-(3-methoxyphenoxy)-2,3-dihydro-1λ6,2,4-benzothiadiazine 1,1-dioxide
• CAS: 1314805-66-7
• 化学式: C₁₇H₁₈N₂O₄S
• 分子量: 346.407
• InChiKey: CTMHATKTIDUKBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  76.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以50%的产率得到4-cyclopropyl-7-(3-hydroxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-1,1-dioxide
  参考文献：
  名称：

  Radiosynthesis of a carbon-11-labeled AMPAR allosteric modulator as a new PET radioligand candidate for imaging of Alzheimer’s disease

  摘要：

  To develop PET tracers for imaging of Alzheimer's disease, a new carbon-11-labeled AMPAR allosteric modulator 4-cyclopropyl-7-(3-[C-11] methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide ([C-11] 8) has been synthesized. The reference standard 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide (8) and its corresponding desmethylated precursor 4-cyclopropyl-7-(3-hydroxyphenoxy)3,4- dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide (9) were synthesized from 4-methoxyabiline and chlorosulfonyl isocyanate in eight and nine steps with 3% and 1% overall chemical yield, respectively. The target tracer [C-11] 8 was prepared from the precursor 9 with [C-11] CH3OTf through O-[C-11] methylation and isolated by HPLC combined with SPE in 10-15% radiochemical yield, based on [C-11] CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was> 99%, and the molar activity (AM) at EOB was 370-740 GBq/mu mol with a total synthesis time of 35-40-minutes from EOB.

  DOI：

  10.1016/j.bmcl.2019.03.027
• 作为产物：
  描述：

  2-氨基-5-甲氧基-苯磺酰胺 在 吡啶 、 sodium tetrahydroborate 、 三氟化硼乙醚 、 copper diacetate 、 三溴化硼 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 异丙醇 为溶剂， 反应 65.17h， 生成 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide
  参考文献：
  名称：

  Radiosynthesis of a carbon-11-labeled AMPAR allosteric modulator as a new PET radioligand candidate for imaging of Alzheimer’s disease

  摘要：

  To develop PET tracers for imaging of Alzheimer's disease, a new carbon-11-labeled AMPAR allosteric modulator 4-cyclopropyl-7-(3-[C-11] methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide ([C-11] 8) has been synthesized. The reference standard 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide (8) and its corresponding desmethylated precursor 4-cyclopropyl-7-(3-hydroxyphenoxy)3,4- dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide (9) were synthesized from 4-methoxyabiline and chlorosulfonyl isocyanate in eight and nine steps with 3% and 1% overall chemical yield, respectively. The target tracer [C-11] 8 was prepared from the precursor 9 with [C-11] CH3OTf through O-[C-11] methylation and isolated by HPLC combined with SPE in 10-15% radiochemical yield, based on [C-11] CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was> 99%, and the molar activity (AM) at EOB was 370-740 GBq/mu mol with a total synthesis time of 35-40-minutes from EOB.

  DOI：

  10.1016/j.bmcl.2019.03.027

文献信息

• Radiosynthesis and preliminary evaluation of 11C-labeled 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e] [1,2,4] thiadiazine 1,1-dioxide for PET imaging AMPA receptors
  作者：Jiahui Chen、Jiefeng Gan、Jiyun Sun、Zhen Chen、Hualong Fu、Jian Rong、Xiaoyun Deng、Jingjie Shang、Jian Gong、Tuo Shao、Lee Collier、Lu Wang、Hao Xu、Steven H. Liang

  DOI：10.1016/j.tetlet.2020.151635

  日期：2020.3

  neurological disorders and neurodegenerative diseases. Inspired by a recently developed positive allosteric modulator of AMPARs, 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1], [2], [4]thiadiazine 1,1-dioxide (16; EC50 = 2.0 nM), we designed a new synthetic route for N-protected phenolic precursor 13 and efficiently radiolabeled a PET ligand [11C]AMPA-1905 ([11C]16) using a modified one-pot

  该α -氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（的AMPARs）属于家族离子型跨膜受体谷氨酸（离子型谷氨酸受体），其在神经系统疾病和神经变性疾病的病理学牵连的。受最近开发的AMPAR的正变构调节剂的启发，4-环丙基-7-（3-甲氧基苯氧基）-3,4-二氢-2 H-苯并[ e ] [1]，[2]，[4]噻二嗪1 1-二氧化物（16 ; EC 50 = 2.0 nM），我们为N保护的酚类前体13设计了一条新的合成路线，并有效地对PET配体进行了放射性标记[ 11 C] AMPA-1905（[ 11 C]16）在高放射化学产率和高摩尔活性中使用改良的一锅两步策略。进行了初步的体内评估，以研究[ 11 C] 16作为AMPAR成像的潜在PET探针的适用性。
• 7-Phenoxy-Substituted 3,4-Dihydro-2<i>H</i>-1,2,4-benzothiadiazine 1,1-Dioxides as Positive Allosteric Modulators of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors with Nanomolar Potency
  作者：Eric Goffin、Thomas Drapier、Anja Probst Larsen、Pierre Geubelle、Christopher P. Ptak、Saara Laulumaa、Karoline Rovinskaja、Julie Gilissen、Pascal de Tullio、Lars Olsen、Karla Frydenvang、Bernard Pirotte、Julien Hanson、Robert E. Oswald、Jette Sandholm Kastrup、Pierre Francotte

  DOI：10.1021/acs.jmedchem.7b01323

  日期：2018.1.11

  coefficient in the screening and the shape of the dimerization curve in small-angle X-ray scattering (SAXS) experiments using isolated GluA2 ligand-binding domain (GluA2-LBD) are consistent with binding of one molecule of 11m per dimer interface, contrary to most benzothiadiazine dioxides developed to date. This observation was confirmed by the X-ray structure of 11m bound to GluA2-LBD and by NMR. This is

  我们在这里报告7-苯氧基取代的3,4-二氢-2 H -1,2,4-苯并噻二嗪1,1-二氧化物的合成及其作为AMPA受体阳性变构调节剂（AMPApams）的评估。考察了取代对苯氧基和4-位氮原子的影响。在HEK293细胞中表达的GluA2（Q）处（钙通量实验），最有效的化合物是11m（4-环丙基-7-（3-甲氧基苯氧基）-3,4-二氢-2 H -1,2,4-苯并噻二嗪1,1-二氧化物，EC 50= 2.0 nM）。使用隔离的GluA2配体结合结构域（GluA2-LBD）进行的小角X射线散射（SAXS）实验中的筛选中的Hill系数和二聚化曲线的形状与每个二聚体界面结合一个11m的分子是一致的，与迄今为止开发的大多数苯并噻二嗪二氧化物相反。通过与GluA2-LBD结合的11m的X射线结构和NMR证实了该观察结果。这是第一个达到纳摩尔范围的二氧化苯并噻二嗪二甲酰胺。
• [EN] NOVEL DERIVATIVES OF CYCLOPROPYLATED BENZOTHIADIAZINES, METHOD FOR PREPARING SAME AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME<br/>[FR] NOUVEAUX DERIVES DE BENZOTHIADIAZINES CYCLOPROPYLEES, LEUR PROCEDE DE PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT
  申请人：SERVIER LAB

  公开号：WO2011083265A1

  公开（公告）日：2011-07-14

  Composés de formule (I) : dans laquelle R1 et R2, identiques ou différents, représentent chacun un atome d'hydrogène ou d'halogène, ou un groupement cyano, hydroxy, thio, nitro, alkyle, alkoxy, alkylthio, carboxy, alkoxycarbonyle, acyloxy, amino, acylamino, aminocarbonyle, aminosulfonyle, alkylsulfonylamino ou N-hydroxycarboximidamide, Médicaments.
• Radiosynthesis of a carbon-11-labeled AMPAR allosteric modulator as a new PET radioligand candidate for imaging of Alzheimer’s disease
  作者：Caihong Miao、Fugui Dong、Limeng Jia、Wei Li、Min Wang、Qi-Huang Zheng、Zhidong Xu

  DOI：10.1016/j.bmcl.2019.03.027

  日期：2019.5

  To develop PET tracers for imaging of Alzheimer's disease, a new carbon-11-labeled AMPAR allosteric modulator 4-cyclopropyl-7-(3-[C-11] methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide ([C-11] 8) has been synthesized. The reference standard 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide (8) and its corresponding desmethylated precursor 4-cyclopropyl-7-(3-hydroxyphenoxy)3,4- dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide (9) were synthesized from 4-methoxyabiline and chlorosulfonyl isocyanate in eight and nine steps with 3% and 1% overall chemical yield, respectively. The target tracer [C-11] 8 was prepared from the precursor 9 with [C-11] CH3OTf through O-[C-11] methylation and isolated by HPLC combined with SPE in 10-15% radiochemical yield, based on [C-11] CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was> 99%, and the molar activity (AM) at EOB was 370-740 GBq/mu mol with a total synthesis time of 35-40-minutes from EOB.