(S)-9-acetoxy-4-ethyl-4-hydroxy-1,12-dihydro-4H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione | 19685-11-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: (S)-9-acetoxy-4-ethyl-4-hydroxy-1,12-dihydro-4H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione
• 英文别名: 10-acetoxycamptothecin；10-acetoxy-camptothecin；[(19S)-19-ethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaen-7-yl] acetate
• CAS: 19685-11-1
• 化学式: C₂₂H₁₈N₂O₆
• 分子量: 406.395
• InChiKey: FLRKIBXXSLMPCA-QFIPXVFZSA-N

物化性质

• 沸点：
  794.2±60.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-9-acetoxy-4-ethyl-4-hydroxy-1,12-dihydro-4H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione 、 溶剂黄146 生成 10-羟基喜树碱
  参考文献：
  名称：

  KINGSBURY, WILLIAM D.;BOEHM, JEFFREY C.;JAKAS, DALIA R.;HOLDEN, KENNETH G+, J. MED. CHEM., 34,(1991) N, C. 98-107

  摘要：

  DOI：
• 作为产物：
  描述：

  喜树碱 在 platinum(IV) oxide lead(IV) acetate 、 硫酸 、 氢气 、 双氧水 、 溶剂黄146 、 三氟乙酸 作用下， 以 1,4-二氧六环 为溶剂， 25.0~80.0 ℃ 、101.33 kPa 条件下， 反应 4.25h， 生成 (S)-9-acetoxy-4-ethyl-4-hydroxy-1,12-dihydro-4H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione
  参考文献：
  名称：

  Synthesis and Antitumor Activity of 20(S)-Camptothecin Derivatives: A-Ring Modified and 7,10-Disubstituted Camptothecins.

  摘要：

  在A环上具有硝基、氨基、氯、溴、羟基和甲氧基的20(S)-喜树碱衍生物被合成出来。通过在三氟乙酸中用四乙酸铅处理，B环氢化的喜树碱（2a）被转化为10-羟基喜树碱（6e）。通过N-氧化物（9）的光反应得到了10-取代的衍生物（6）。对A环修饰的喜树碱的细胞毒性进行了体外KB细胞和小鼠中的白血病L1210的评估。鉴定出7-乙基-10-羟基喜树碱（6i）作为一个有潜力的衍生物，可进一步进行修饰。

  DOI：

  10.1248/cpb.39.3183

文献信息

• Camptothecin derivatives and process for preparing same
  申请人：Kabushiki Kaisha Yakult Honsha

  公开号：US04473692A1

  公开（公告）日：1984-09-25

  New Camptothecin derivatives possessing high anti-tumor activity with slight toxicity, represented by the general formula: ##STR1## wherein R.sup.1 is a hydrogen atom, an alkyl group, a hydroxyl group, an alkoxy group or an acyloxy group, R.sup.2 for a hydrogen atom, an alkyl group, an aralkyl group, a hydroxymethyl group, a carboxymethyl group or an acyloxymethyl group, and R.sup.3 is the grouping --XR' (where R' is a hydrogen atom, an alkyl group or an acyl group and X is an oxygen atom or a sulfur atom), a nitro group, an amino group, an alkylamino group, an acylamino group or a halogen atom, with the proviso that when both of R.sup.1 and R.sup.2 are hydrogen atoms, R.sup.3 should not be a hydroxyl group, methoxy group or acetoxy group. These new camptothecin derivatives are prepared by treating a 5-R.sup.1 -7-R.sup.2 -camptothecin derivative with a peroxidant and then reacting the resultant 5-R.sup.1 -7-R.sup.2 -camptothecin-1-oxide with an active hydrogen compound under irradiation of UV-rays or by catalytically hydrogenating the ring B of camptothecin in a solvent, treating the resultant tetrahydro product with an acylating agent, introducing a nitro group into the 10-position of the acylated product by the reaction with nitric acid, splitting off the acyl group in the 10-nitro product by hydrolysis and treating the hydrolyzed tetrahydro product with an oxidizing agent for dehydrogenation, and if desired, reducing the nitro group in the resulting product to an amino group and modifying the amino group by N-alkylation, N-acylation or by diazotization followed by hydrolysis or the Sandmeyer reaction, before or after the oxidation of the 10-nitro-tetrahydro product.

  新的喜树碱衍生物具有高抗肿瘤活性，毒性轻微，其一般式表示为：##STR1##其中R.sup.1为氢原子、烷基、羟基、烷氧基或酰氧基，R.sup.2为氢原子、烷基、芳基烷基、羟甲基、羧甲基或酰氧甲基，R.sup.3为基团--XR'（其中R'为氢原子、烷基或酰基，X为氧原子或硫原子），亚硝基、氨基、烷基氨基、酰胺基或卤素原子，但是当R.sup.1和R.sup.2均为氢原子时，R.sup.3不应为羟基、甲氧基或乙酰氧基。这些新的喜树碱衍生物是通过将5-R.sup.1-7-R.sup.2-喜树碱衍生物与过氧化剂处理，然后在紫外线照射下将所得的5-R.sup.1-7-R.sup.2-喜树碱-1-氧化物与活性氢化合物反应，或者在溶剂中催化氢化喜树碱的B环，处理所得的四氢产物与酰化剂反应，通过与硝酸反应将亚硝基引入酰化产物的10位，通过水解将10-亚硝基产物中的酰基分离，并将水解后的四氢产物与氧化剂处理以脱氢，如有需要，将所得产物中的亚硝基还原为氨基，并通过N-烷基化、N-酰化或通过重氮化后水解或桑迈尔反应修饰氨基团，在氧化10-亚硝基四氢产物之前或之后。
• [EN] PROCESS FOR PREPARING TOPOTECAN FROM 10-HYDROXY-4-(S) CAMPTOTHECIN<br/>[FR] PROCEDE POUR PREPARER DU TOPOTECAN A PARTIR DE 10-HYDROXY-4-(S)-CAMPTOTHECINE
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2004087715A1

  公开（公告）日：2004-10-14

  The present invention relates to the use of dihalomethanes as reagents for the preparation of Topotecan 4-(S)-10 (dimethylamino)-methyl-4-ethyl 4, 9 dihydroxyl-H-pyrano [3'4': 6,7] indolizino-[1,2-b]quinoline-3,14 (4H,12H)dione} from 10-hydroxycamptothecin. The invention discloses the rationale use of dichloromethane under solid-liquid phase transfer catalysis, which can behave both as solvent and a reactant when it serves as a source for C-1 unit for amino-alkylation of 10-hydroxy-4-(S) camptothecin.

  本发明涉及二卤甲烷作为试剂，用于从10-羟基喜树碱制备托泊替康4-(S)-10(二甲基氨基)-甲基-4-乙基-4,9-二羟基-H-吡喁[3'4':6,7]吲哩啉-[1,2-b]喹啉-3,14(4H,12H)二酮}。该发明揭示了二氯甲烷在固-液相转移催化下的合理使用，当作为C-1单位的来源用于10-羟基-4-(S)-喜树碱的氨基烷基化时，它既可以作为溶剂，也可以作为反应物。
• Process for preparing Topotecan from 10-hydroxy-4-(S) camptothecin
  申请人：Council of Scientific and Industrial Research

  公开号：US06660861B1

  公开（公告）日：2003-12-09

  The present invention relates to the use of dihalomethanes as reagents for the preparation of Topotecan{4-(S)-10(dimethylamino)-methyl-4-ethyl 4,9 dihydroxyl-H-pyrano[3′4′:6,7]indolizino-[1,2-b]quinoline-3,14(4H,12H)dione} from 10-hydroxycamptothecin. The invention discloses the rationale use of dichloromethane under solid-liquid phase transfer catalysis, which can behave both as solvent and a reactant when it serves as a source for C-1 unit for amino-alkylation of 10-hydroxy-4-(S)camptothecin.

  本发明涉及二卤甲烷作为试剂，用于制备托泊替康（4-(S)-10(二甲氨基)-甲基-4-乙基-4,9-二羟基-H-吡喜烯并吡啶并喹啉-3,14(4H,12H)-二酮）从10-羟基喜树碱。该发明揭示了二氯甲烷在固-液相转移催化下的合理用途，当其作为C-1单位的来源用于10-羟基-4-(S)-喜树碱的氨基烷基化时，它既可以作为溶剂，也可以作为反应物。
• COMBINATIONS COMPRISING BCR-ABL/C-KIT/PDGF-R TK INHIBITORS FOR TREATING CANCER
  申请人：Burke Gregory Peter

  公开号：US20090233905A1

  公开（公告）日：2009-09-17

  The invention relates to a combination comprising a Bcr-Abl, c-Kit and PDGF-R tyrosine kinase inhibitor; and one or more pharmaceutically active agents; pharmaceutical compositions comprising said combination; methods of treatment comprising said combination; processes for making said combination; and a commercial package comprising said combination.

  本发明涉及一种组合物，包括Bcr-Abl、c-Kit和PDGF-R酪氨酸激酶抑制剂；以及一种或多种药物活性剂；包括该组合物的制药组合物；包括该组合物的治疗方法；制备该组合物的过程；以及包括该组合物的商业包装。
• COMBINATION OF IAP INHIBITORS AND FLT3 INHIBITORS
  申请人：Griffin James Douglas

  公开号：US20100056467A1

  公开（公告）日：2010-03-04

  The present invention relates to methods of treating hematological malignancies, including acute myeloid leukemia (AML), comprising the combination of a compound that inhibits the binding of the Smac protein to IAPs (“IAP inhibitor”) and one or more pharmaceutically active agents; pharmaceutical compositions comprising said combination; and a commercial package comprising said combination. The present invention also relates to the use of IAP inhibitors in combination with one or more pharmaceutically active agents for the preparation of a medicament to treat hematological malignancies, including AML.

  本发明涉及治疗血液系统恶性肿瘤的方法，包括急性髓系白血病（AML），其中包括抑制Smac蛋白与IAP结合的化合物（“IAP抑制剂”）与一种或多种药物活性剂的组合；包含该组合的药物组合物；以及包含该组合的商业包装。本发明还涉及使用IAP抑制剂与一种或多种药物活性剂的组合制备药物来治疗血液系统恶性肿瘤，包括AML。