6-p-methoxyphenylpyrrolo<2,1-d><1,5>benzothiazepin-7(6H)-one | 131403-74-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: 6-p-methoxyphenylpyrrolo<2,1-d><1,5>benzothiazepin-7(6H)-one
• 英文别名: (+/-)-6-(4-methoxyphenyl)pyrrolo[2,1-d][1,5]benzothiazepin-7(6H)-one；6-p-methoxyphenylpyrrolo[2,1-d][1,5]benzothiazepin-7(6H)-one；5-(4-Methoxy-phenyl)-6-thia-10b-aza-benzo[e]azulen-4-one；6-(4-methoxyphenyl)pyrrolo[2,1-d][1,5]benzothiazepin-7-one
• CAS: 131403-74-2
• 化学式: C₁₉H₁₅NO₂S
• 分子量: 321.4
• InChiKey: FNPSYYAODVMBAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-p-methoxyphenylpyrrolo<2,1-d><1,5>benzothiazepin-7(6H)-one 在 lithium aluminium tetrahydride 、 sodium acetate 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 cis-7-acetoxy-6,7-dihydro-6-p-methoxyphenylpyrrolo<2,1-d><1,5>-benzothiazepine
  参考文献：
  名称：

  Nacci; Fiorini; Garofalo, Il Farmaco, 1990, vol. 45, # 5, p. 545 - 557

  摘要：

  DOI：
• 作为产物：
  描述：

  2-(1H-吡咯-1-基)苯硫醇 在 sodium hydroxide 、 三氯化铝 、 乙醇 、 五氯化磷 、 sodium 作用下， 以 乙醇 为溶剂， 反应 39.25h， 生成 6-p-methoxyphenylpyrrolo<2,1-d><1,5>benzothiazepin-7(6H)-one
  参考文献：
  名称：

  Nacci; Fiorini; Garofalo, Il Farmaco, 1990, vol. 45, # 5, p. 545 - 557

  摘要：

  DOI：

文献信息

• Novel Ligands Specific for Mitochondrial Benzodiazepine Receptors: 6-arylpyrrolo[2,1-d][1,5]benzothiazepine Derivatives. Synthesis, Structure-Activity Relationships, and Molecular Modeling Studies
  作者：Isabella Fiorini、Vito Nacci、Silvia Maria Ciani、Antonio Garofalo、Giuseppe Campiani、Luisa Savini、Ettore Novellino、Gianni Greco、Paola Bernasconi、Tiziana Mennini

  DOI：10.1021/jm00036a007

  日期：1994.5

  important structural features improving affinity. Therefore, 7-[(dimethylcarbamoyl)oxy]- and 7-acetoxy-4-chloro-6-phenylpyrrolo[2,1-d][1,5]benzothiazepine (43 and 57) were synthesized. With 7-[(dimethylcarbamoyl)oxy]-6-(p-methoxyphenyl)pyrrolo[2,1- d][1,5]benzothiazepine (65), these were the most promising compounds with IC50s of respectively 9, 8, and 9 nM, under conditions where PK 11195 had an IC50

  已鉴定出一类新的对MBR受体具有特异性的配体：6-芳基吡咯并[2,1-d] [1,5]苯并硫氮杂derivatives衍生物。大多数新合成的酯37-64以及一些中间酮对[3H] PK 11195的结合抑制表现出微摩尔或纳摩尔的亲和力。一项对42种化合物的SAR研究和分子建模方法得出了初步的结构选择性特征：6,7-双键，7位的氨基甲酰氧基，alcanoyloxy和甲磺酰氧基侧链以及4位的预期氯取代位置似乎是提高亲和力的最重要的结构特征。因此，合成了7-[（（二甲基氨基甲酰基）氧基]-和7-乙酰氧基-4-氯-6-苯基吡咯并[2，1-d] [1，5]苯并硫氮杂（（43和57）。与7-[（二甲基氨基甲酰基）氧基] -6-（对甲氧基苯基）吡咯并[2,1- d] [1,5]苯并噻氮平（65），
• Pyrrolo[1,5]benzoxa(thia)zepines as a New Class of Potent Apoptotic Agents. Biological Studies and Identification of an Intracellular Location of Their Drug Target
  作者：Margaret M. Mc Gee、Sandra Gemma、Stefania Butini、Anna Ramunno、Daniela M. Zisterer、Caterina Fattorusso、Bruno Catalanotti、Gagan Kukreja、Isabella Fiorini、Claudio Pisano、Carla Cucco、Ettore Novellino、Vito Nacci、D. Clive Williams、Giuseppe Campiani

  DOI：10.1021/jm049402y

  日期：2005.6.1

  We have recently developed five novel pyrrolo-1,5-benzoxazepines as proapoptotic agents. Their JNK-dependent induction of apoptosis in tumor cells suggested their potential as novel anticancer agents. The core structure of the apoptotic agent 6 was investigated, and the SARs were expanded with the design and synthesis of several analogues. To define the apoptotic mechanism of the new compounds and the localization of their drug target, two analogues of 6 were designed and synthesized to delineate events leading to JNK activation. The cell-penetrating compound 16 induced apoptosis in tumor cells, while its nonpenetrating analogue, 17, was incapable of inducing apoptosis or activating JNK. Plasma membrane permeabilization of tumor cells resulted in 17-induced JNK activation, suggesting that the pyrrolo-1,5-benzoxazepine molecular target is intracellular. Interestingly, compound 6 displayed cytotoxic activity against a panel of human tumor cell lines but demonstrated negligible toxicity in vivo with no effect on the animals' hematology parameters.
• NACCI, VITO;FIORINI, ISABELLA;GAROFALO, ANTONIO;GAGNOTTO, ALFREDO, FARMACO, 45,(1990) N, C. 545-557
  作者：NACCI, VITO、FIORINI, ISABELLA、GAROFALO, ANTONIO、GAGNOTTO, ALFREDO

  DOI：——

  日期：——
• US6806267B1
  申请人：——

  公开号：US6806267B1

  公开（公告）日：2004-10-19