5-ethyl-4,5-dihydro-5-hydroxy-9-methoxyoxepino<3,4-c>pyridin-3(1H)-one | 186668-53-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-ethyl-4,5-dihydro-5-hydroxy-9-methoxyoxepino<3,4-c>pyridin-3(1H)-one
• 英文别名: 5-ethyl-5-hydroxy-1-methoxy-5,9-dihydro-6H-8-oxa-2-aza-benzocyclohepten-7-one；(+)-(5R)-5-Ethyl-5-hydroxy-1-methoxy-5.6-dihydro-9H-8-oxa-2-aza-benzocyclohepten-7-one；5-ethyl-5-hydroxy-9-methoxy-4,5-dihydrooxepino[3,4-c]pyridin-3(1H)-one；5-ethyl-5-hydroxy-9-methoxy-1,4-dihydrooxepino[3,4-c]pyridin-3-one
• CAS: 186668-53-1
• 化学式: C₁₂H₁₅NO₄
• 分子量: 237.255
• InChiKey: DPVIBNQFGDJPHG-UHFFFAOYSA-N

物化性质

• 熔点：
  118 °C
• 沸点：
  459.4±45.0 °C(Predicted)
• 密度：
  1.237±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  68.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-ethyl-4,5-dihydro-5-hydroxy-9-methoxyoxepino<3,4-c>pyridin-3(1H)-one 在 氢溴酸 作用下， 以 乙二醇二甲醚 为溶剂， 反应 17.5h， 以61%的产率得到(+)-5-ethyl-5-hydroxy-1,3,4,5,8,9-hexahydrooxepino[3,4-c]pyridin-3,9-dione
  参考文献：
  名称：

  高喜树碱衍生物和抗癌剂二氟莫替康的实用外消旋和不对称形式全合成通过叔高烯丙醇作为掩蔽的羟醛等价物

  摘要：

  描述了一种有效且可扩展的外消旋和不对称方法，用于合成高喜树碱及其衍生物（如强效抗癌剂二氟莫替康 (4)）的关键构件。在不对称路线中，吡啶酮环是通过简单的羰基化学组装而成的。季立体中心的选择性生成是通过从 (S)-2-羟基丁酸 (22) 开始的手性信息的自我复制来完成的，该信息利用烯丙基部分作为掩蔽的羰基。经过 10 个步骤（两次色谱纯化），以 9.0% 的总产率获得了光学纯 DE 结构单元 (7) (er > 99.95: 0.05)。不对称的“从头吡啶酮方法”有可能成为二氟莫替康技术合成的基础。

  DOI：

  10.3987/com-06-s(k)10
• 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 12.17h， 生成 5-ethyl-4,5-dihydro-5-hydroxy-9-methoxyoxepino<3,4-c>pyridin-3(1H)-one
  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。
• Intermediates and methods of preparation of intermediates in the enantiomeric synthesis of (20R)homocamptothecins and the enantiomeric synthesis of (20R)homocamptothecins
  申请人：——

  公开号：US20030073840A1

  公开（公告）日：2003-04-17

  A method of synthesizing a compound having the formula: 1 from a compound having the formula: 2 wherein R 1 is hydrogen, fluorine, chlorine or SiR 5 R 6 R 7 , wherein R 5 , R 6 , and R 7 are independently the same or different an alkyl group or an aryl group, R 2 is an alkyl group, R 3 is a protecting group, R 4 is an alkyl group, an allyl group, a propargyl group —CO 2 H, or a benzyl group, R 8 is —CO 2 R 10 , wherein R 10 is an alkyl group or an aryl group, X 1 is OH and X 2 is H, includes the step of exposing compound (III) to at least one of an organic acid or an inorganic acid. A compound has the general formula (III).

  一种合成具有以下化学式的化合物的方法：1从具有以下化学式的化合物中进行：2其中R1为氢、氟、氯或SiR5R6R7，其中R5、R6和R7分别独立地为相同或不同的烷基基团或芳基基团，R2为烷基基团，R3为保护基团，R4为烷基基团、烯丙基团、丙炔基团、—CO2H或苄基团，R8为—CO2R10，其中R10为烷基基团或芳基基团，X1为OH，X2为H，包括将化合物(III)暴露于至少一种有机酸或无机酸中的步骤。化合物具有一般化学式(III)。
• 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。
• Analogues of camptothecin, their use as medicaments and the pharmaceutical compositions containing them
  申请人：Societe de Recherches et d'Applications Scientifiques (S.C.R.A.S.)

  公开号：US06815546B2

  公开（公告）日：2004-11-09

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

  该化合物的化学式，其中取代基的定义如规范中所述，这些化合物在癌症治疗中很有用。
• FORMES PRODROGUES ET ANALOGUES DE LA CAMPTOTHECINE, LEUR APPLICATION COMME MEDICAMENTS
  申请人：SOCIETE DE CONSEILS DE RECHERCHES ET D'APPLICATIONS SCIENTIFIQUES (S.C.R.A.S.)

  公开号：EP0946566B1

  公开（公告）日：2003-11-05