(E)-3-(1-(3-fluoro-8-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)dibenzo[b,e]oxepin-11(6H)-ylidene)ethyl)-1,2,4-oxadiazol-5(4H)-one | 1421783-66-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噁庚英
• 英文名称: (E)-3-(1-(3-fluoro-8-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)dibenzo[b,e]oxepin-11(6H)-ylidene)ethyl)-1,2,4-oxadiazol-5(4H)-one
• 英文别名: 3-[(1E)-1-[3-fluoro-8-[(2-propylbenzimidazol-1-yl)methyl]-6H-benzo[c][1]benzoxepin-11-ylidene]ethyl]-4H-1,2,4-oxadiazol-5-one
• CAS: 1421783-66-5
• 化学式: C₂₉H₂₅FN₄O₃
• 分子量: 496.541
• InChiKey: PBUIWUMZZZXLAE-WPWMEQJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  77.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-bromo-2-((3-fluorophenoxy)methyl)benzoic acid 在 2,6-二甲基吡啶 、 锂硼氢 、 三氟化硼乙醚 、 1,3-双(二苯基膦)丙烷 、 羟胺 、 palladium diacetate 、 potassium carbonate 、 caesium carbonate 、 三氟乙酸酐 、 lithium bromide 、 lithium diisopropyl amide 、 甲基磺酸酐 作用下， 以 四氢呋喃 、 乙醇 、 正庚烷 、 二氯甲烷 、 乙基苯 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.08h， 生成 (E)-3-(1-(3-fluoro-8-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)dibenzo[b,e]oxepin-11(6H)-ylidene)ethyl)-1,2,4-oxadiazol-5(4H)-one
  参考文献：
  名称：

  DIBENZOOXEPIN DERIVATIVE

  摘要：

  公开号：

  EP2740730B1

文献信息

• Development of a novel class of peroxisome proliferator-activated receptor (PPAR) gamma ligands as an anticancer agent with a unique binding mode based on a non-thiazolidinedione scaffold
  作者：Keisuke Yamamoto、Tomohiro Tamura、Rina Nakamura、Shintaro Hosoe、Masahiro Matsubara、Keiko Nagata、Hiroshi Kodaira、Takeshi Uemori、Yuichi Takahashi、Michihiko Suzuki、Jun-ichi Saito、Kimihisa Ueno、Satoshi Shuto

  DOI：10.1016/j.bmc.2019.115122

  日期：2019.11

  We previously identified dibenzooxepine derivative 1 as a potent PPAR. ligand with a unique binding mode owing to its non-thiazolidinedione scaffold. However, while 1 showed remarkably potent MKN-45 gastric cancer cell aggregation activity, an indicator of cancer differentiation-inducing activity induced by PPAR. activation, we recognized that 1 was metabolically unstable. In the present study, we identified a metabolically soft spot, and successfully discovered 3-fluoro dibenzooxepine derivative 9 with better metabolic stability. Further optimization provided imidazo[1,2-alpha]pyridine derivative 17, which showed potent MKN-45 gastric cancer cell aggregation activity and excellent PK profiles compared with 9. Compound 17 exerted a growth inhibitory effect on AsPC-1/AG1 pancreatic tumor in mice. Furthermore, the decrease in the hematocrit (an indicator of localized edema, a serious adverse effect of PPAR gamma ligands) was tolerable even with oral administration at 200 mg/kg in healthy mice.
• ANALOGUES OF CILOSTAZOL
  申请人：CONCERT PHARMACEUTICALS INC.

  公开号：US20130131021A1

  公开（公告）日：2013-05-23

  This invention relates to novel compounds which are derivatives of the phosphodiesterase inhibitor, cilostazol and pharmaceutically acceptable salts thereof. This invention also provides pyrogen-free compositions comprising one or more compounds of the invention and the use of the disclosed compounds and compositions in methods of treating diseases and conditions that are treated by administration of a phosphodiesterase inhibitor, such as cilostazol. The invention also relates to the use of the disclosed compounds and compositions as reagents in analytical studies involving cilostazol.
• US8969345B2
  申请人：——

  公开号：US8969345B2

  公开（公告）日：2015-03-03
• DIBENZOOXEPIN DERIVATIVE
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：EP2740730B1

  公开（公告）日：2016-11-16