(+)-5-ethyl-5-hydroxy-1,3,4,5,8,9-hexahydrooxepino[3,4-c]pyridin-3,9-dione | 186668-54-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (+)-5-ethyl-5-hydroxy-1,3,4,5,8,9-hexahydrooxepino[3,4-c]pyridin-3,9-dione
• 英文别名: 5-ethyl-1,4,5,8-tetrahydro-5-hydroxyoxepino<3,4-c>pyridine-3,9-dione；5-ethyl-5-hydroxy-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione；5-ethyl-1,5dihydro-5-hydroxy-oxepino [3,4-c] pyridine 3,9(4H,8H)-dione；5-ethyl-5-hydroxy-4,8-dihydro-1H-oxepino[3,4-c]pyridine-3,9-dione
• CAS: 186668-54-2
• 化学式: C₁₁H₁₃NO₄
• 分子量: 223.229
• InChiKey: RVBWWMADTISCJE-UHFFFAOYSA-N

物化性质

• 熔点：
  >210 °C (decomp)
• 沸点：
  607.9±55.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-5-ethyl-5-hydroxy-1,3,4,5,8,9-hexahydrooxepino[3,4-c]pyridin-3,9-dione 在 palladium diacetate 、 t-Bu₃Ph 、 四丁基溴化铵 、 sodium acetate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 39.0h， 生成 9-chloro-5-ethyl-5-hydroxy-10-methyl-1,4,5,13-tetrahydro-3H,15H-oxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione
  参考文献：
  名称：

  Homocamptothecins:  Synthesis and Antitumor Activity of Novel E-Ring-Modified Camptothecin Analogues

  摘要：

  Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered beta-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c,d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell. lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.

  DOI：

  10.1021/jm980400l
• 作为产物：
  描述：

  1-{3-[(benzyloxy)methyl]-2-methoxy-4-pyridinyl}-1-propanone 在 palladium on activated charcoal 盐酸 、 氢气 、 三氟乙酸 、 锌 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 21.17h， 生成 (+)-5-ethyl-5-hydroxy-1,3,4,5,8,9-hexahydrooxepino[3,4-c]pyridin-3,9-dione
  参考文献：
  名称：

  Homocamptothecins:  Synthesis and Antitumor Activity of Novel E-Ring-Modified Camptothecin Analogues

  摘要：

  Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered beta-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c,d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell. lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.

  DOI：

  10.1021/jm980400l

文献信息

• Comptothecin analogues, preparation methods therefor, use thereof as drugs, and pharmaceutical compositions containing said analogues
  申请人：Societe de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S.)

  公开号：US06339091B1

  公开（公告）日：2002-01-15

  The compound of the formula wherein the substituents are defined as in the specification and its non-toxic, pharmaceutically acceptable salts which are useful for the treatment of viral infections, parasitic diseases and the treatment of cancer.

  该化合物的结构如下所示，其中取代基的定义如规范中所述，以及其无毒、药用可接受的盐，可用于治疗病毒感染、寄生虫病和癌症的治疗。
• New analogues of camptothecin, their use as medicaments and the pharmaceutical compositions containing them
  申请人：——

  公开号：US20030004150A1

  公开（公告）日：2003-01-02

  A compound of the formula 1 wherein the substituents are defined as in the specification which compounds are useful in the treatment of cancer.

  其中取代基如规范中所定义的化合物的化学式，这些化合物在癌症治疗中很有用。
• Use of phenyl oxazole or phenyl thiazole derivatives for treating neuropathic pain
  申请人：ELI LILLY AND COMPANY

  公开号：EP0906755A2

  公开（公告）日：1999-04-07

  The present invention provides a method for treating neuropathic pain comprising administering an analgesic dosage of a compound of formula I to an animal in need of such treatment certain phenyl oxazoles or phenyl thiazoles.

  本发明提供了一种治疗神经性疼痛的方法，包括向需要此类治疗的动物施用化合物I的镇痛剂量，该化合物为特定的苯并噁唑或苯并噻唑。
• Use of phenyl oxazole or phenyl thiazole derivatives for treating pain
  申请人：ELI LILLY AND COMPANY

  公开号：EP0908180A2

  公开（公告）日：1999-04-14

  The present invention provides a method for treating pain comprising administering to an animal in need of such treatment, an analgesic dosage of certain phenyl oxazoles or phenyl thiazoles.

  本发明提供了一种治疗疼痛的方法，包括向需要此类治疗的动物施用一定剂量的苯并噁唑或苯并噻唑类镇痛药。
• Method for treating pain
  申请人：ELI LILLY AND COMPANY

  公开号：EP0908186A3

  公开（公告）日：1999-04-21

  The present invention provides a method for treating pain using a composition comprising certain phenyl oxazoles or phenyl thiazoles in combination with a Drug Useful in the Treatment of Pain.

  本发明提供了一种使用包含特定苯基噁唑或苯基噻唑与用于治疗疼痛的有效药物组合的组合物来治疗疼痛的方法。