propyl 11-(1-cyanoethylidene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepin-8-carboxylate | 1421787-81-6

• 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: propyl 11-(1-cyanoethylidene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepin-8-carboxylate
• 英文别名: propyl 11-(1-cyanoethylidene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepine-8-carboxylate；Propyl 11-(1-cyanoethylidene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepin-8-carboxylate；propyl 11-(1-cyanoethylidene)-3-fluoro-6H-benzo[c][1]benzoxepine-8-carboxylate
• CAS: 1421787-81-6
• 化学式: C₂₁H₁₈FNO₃
• 分子量: 351.377
• InChiKey: OVBLGQHBXFFALB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  propyl 11-(1-cyanoethylidene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepin-8-carboxylate 在 2,6-二甲基吡啶 、 锂硼氢 、 羟胺 、 potassium carbonate 、 lithium bromide 、 甲基磺酸酐 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 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：

  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

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2019.115122
• 作为产物：
  描述：

  3-氟苯酚 在 三氟化硼乙醚 、 1,3-双(二苯基膦)丙烷 、 sodium methylate 、 palladium diacetate 、 caesium carbonate 、 三氟乙酸酐 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 、 二氯甲烷 、 乙基苯 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.75h， 生成 propyl 11-(1-cyanoethylidene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepin-8-carboxylate
  参考文献：
  名称：

  DIBENZOOXEPIN DERIVATIVE

  摘要：

  公开号：

  EP2740730B1

文献信息

• Dibenzooxepin derivative
  申请人：Yamamoto Keisuke

  公开号：US08969345B2

  公开（公告）日：2015-03-03

  A dibenzoxepin derivative represented by the following general formula (I) wherein Y is a hydrogen atom and the like, RA is a hydrogen atom and the like, X is the formula (b3) wherein RB is a hydrogen atom and the like, and the like, A is the formula (a18) wherein R1 is a hydrogen atom and the like, and RC and RD are the same or different and each is a hydrogen atom and the like, and the like, which has a PPARγ agonist activity and the like, and useful as a therapeutic agent and/or prophylaxis agent and the like for type 2 diabetes and the like, or a pharmaceutically acceptable salt thereof and the like is provided.

  提供了一种二苯并氧吩衍生物，其通式表示为（I），其中Y为氢原子等，RA为氢原子等，X为式（b3），其中RB为氢原子等，A为式（a18），其中R1为氢原子等，RC和RD相同或不同，且每个为氢原子等，该物质具有PPARγ激动剂活性等，可用作治疗和/或预防2型糖尿病等的治疗剂和/或预防剂等，或其药学上可接受的盐等。
• DIBENZOOXEPIN DERIVATIVE
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：EP2740730B1

  公开（公告）日：2016-11-16
• 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.