3-hydroxy-3-(3-hydroxymethyl-4-oxo-4,6-dihydroindolizino<1,2-b>quinolin-2-yl)pentanoic acid | 186668-41-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-hydroxy-3-(3-hydroxymethyl-4-oxo-4,6-dihydroindolizino<1,2-b>quinolin-2-yl)pentanoic acid
• 英文别名: 3-hydroxy-3-[8-(hydroxymethyl)-9-oxo-9,11-dihydroindolizino[1,2-b]quinolin-7-yl]pentanoic acid；3-hydroxy-3-[8-(hydroxymethyl)-9-oxo-11H-indolizino[1,2-b]quinolin-7-yl]pentanoic acid
• CAS: 186668-41-7
• 化学式: C₂₁H₂₀N₂O₅
• 分子量: 380.4
• InChiKey: QEABWTHHJOLILC-UHFFFAOYSA-N

物化性质

• 沸点：
  777.8±60.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-hydroxy-3-(3-hydroxymethyl-4-oxo-4,6-dihydroindolizino<1,2-b>quinolin-2-yl)pentanoic acid 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 68.0h， 生成 5-ethyl-5-hydroxy-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：

  喜树碱 在 sodium hydroxide 、 sodium tetrahydroborate 、 sodium periodate 、 溶剂黄146 、 三氟乙酸 、 锌 作用下， 以 四氢呋喃 为溶剂， 生成 3-hydroxy-3-(3-hydroxymethyl-4-oxo-4,6-dihydroindolizino<1,2-b>quinolin-2-yl)pentanoic acid
  参考文献：
  名称：

  BN 80245: An E-ring modified camptothecin with potent antiproliferative and topoisomerase I inhibitory activities

  摘要：

  The crucial E-ring of camptothecin has been modified to afford the homologous beta-hydroxylactone derivative BN 80245. This compound, which is more stable than camptothecin, remains a potent inhibitor of both cell growth and topoisomerase I. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00398-3

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。
• 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。
• Camptothecin analogs and methods of preparation thereof
  申请人：Curran P. Dennis

  公开号：US20080027224A1

  公开（公告）日：2008-01-31

  A compound having the formula in racemic form, enantiomerically enriched form or enantiomerically pure form; wherein X is a radical precursor; R 5 is a C 1-10 alkyl group, an alkenyl group, an alkynyl group, or a benzyl group; R 6 is an alkyl group, —Si(R 8 R 9 R 10 ) or —(R 7 )Si(R 8 R 9 R 10 ), wherein R 7 is an alkylene group, an alkenylene group, or an alkynylene group; and R 8 , R 9 and R 10 are independently a C 1-10 alkyl group, a C 2-10 alkenyl group, a C 2-10 alkynyl group, an aryl group or a —(CH 2 ) N R 11 group, wherein N is an integer within the range of 1 through 10 and R 11 is a hydroxy group, an alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group, —SR c or a nitro group; and R 13 is H, F or —CH 3 .

  化合物的化学式为：在外消旋形式、对映富集形式或对映纯形式下，其中X是基团前体；R5是C1-10烷基、烯基、炔基或苄基；R6是烷基、—Si（R8R9R10）或—（R7）Si（R8R9R10），其中R7是亚烷基、烯丙基或炔丙基；R8、R9和R10分别是C1-10烷基、C2-10烯基、C2-10炔基、芳基或—（CH2）NR11基团，其中N为1至10的整数，R11是羟基、烷氧基、氨基、烷基氨基、二烷基氨基、卤素原子、氰基、—SR或硝基；R13是H、F或—CH3。
• CAMPTOTHECIN ANALOGS AND METHODS OF PREPARATION THEREOF
  申请人：CURRAN DENNIS P.

  公开号：US20120136153A1

  公开（公告）日：2012-05-31

  A compound having the formula in racemic form, enantiomerically enriched form or enantiomerically pure form, and pharmaceutically acceptable salts thereof.

  一种具有如下式的化合物，包括其外消旋体形式，对映体富集形式或对映体纯形式，以及其药学上可接受的盐。