(9S)-1-butyl-9-ethyl-9-hydroxy-1H,12H-pyrano[3'',4'':6',7']indolizino[1',2':6,5]-pyrido[4,3,2-de]quinazoline-10,13(9H,15H)-dione | 534605-76-0

• 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: (9S)-1-butyl-9-ethyl-9-hydroxy-1H,12H-pyrano[3'',4'':6',7']indolizino[1',2':6,5]-pyrido[4,3,2-de]quinazoline-10,13(9H,15H)-dione
• 英文别名: (9S)-1-butyl-9-ethyl-9-hydroxy-1H,12H-pyrano[3",4":6',7']indolizino[1',2':6,5]pyrido[4,3,2-de]quinazoline-10,13(9H,1 5H)-dione；(9S)-1-butyl-9-ethyl-9-hydroxy-1H,12H-pyrano[3'',4'':6',7']indolizino[1',2':6,5]pyrido-[4,3,2-de]quinazoline-10,13 (9H,15H)-dione；(10S)-23-butyl-10-ethyl-10-hydroxy-8-oxa-4,15,21,23-tetrazahexacyclo[14.7.1.02,14.04,13.06,11.020,24]tetracosa-1,6(11),12,14,16(24),17,19,21-octaene-5,9-dione
• CAS: 534605-76-0
• 化学式: C₂₅H₂₄N₄O₄
• 分子量: 444.49
• InChiKey: ZPXZKFJWQGEQLD-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  95.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (9S)-9-acetoxy-1-butyl-9-ethyl-1H,12H-pyrano[3",4":6',7']indolizino[1',2':6,5]pyrido[4,3,2-de]quinazoline-10,13(9H,15H)-dione 在 肼 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 生成 (9S)-1-butyl-9-ethyl-9-hydroxy-1H,12H-pyrano[3'',4'':6',7']indolizino[1',2':6,5]-pyrido[4,3,2-de]quinazoline-10,13(9H,15H)-dione
  参考文献：
  名称：

  合成具有改进抗肿瘤活性的喜树碱类似物

  摘要：

  基于拓扑异构酶I（Topo I）/ DNA /喜树碱三元复合物的3D结构，设计并合成了含有环am，尿素或硫脲部分的新型六环喜树碱类似物。由9-硝基喜树碱经7，9-二氨基喜树碱衍生物作为关键中间体制备类似物。其中，7c在人类癌症异种移植模型中以最大耐受剂量表现出优于CPT-11的体内抗肿瘤活性，尽管其在体外的抗增殖活性可与SN-38媲美。

  DOI：

  10.1016/j.bmcl.2009.02.031

文献信息

• AGENT FOR PREVENTING OR TREATING PANCREAS CANCER, OVARY CANCER OR LIVER CANCER CONTAINING NOVEL WATER-SOLUBLE PRODRUG
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1938823A1

  公开（公告）日：2008-07-02

  Preventive or therapeutic agents for pancreatic cancer, ovarian cancer, or liver cancer of the present invention comprise a water-soluble prodrug represented by formula 1 described below, or a pharmaceutically acceptable salt, or a hydrate or solvate of the prodrug or pharmaceutically acceptable salt, (wherein, R1 represents a hydrogen atom, or a C1-C6 alkyl group; W represents a divalent group comprising a tertiary amino group or a divalent group comprising a sulfonyl group, and Y represents a residue of a compound represented by Y-OH comprising an alcoholic hydroxyl group, wherein said Y-OH is a camptothecin, a taxane, or an anticancer nucleotide).

  预防或治疗胰腺癌、卵巢癌或肝癌的本发明药剂包括下述式子所代表的水溶性前药，或者前药的药用可接受盐，或者前药或药用可接受盐的水合物或溶剂化合物， （其中， R1代表氢原子，或者C1-C6烷基； W代表包含三级胺基团或含磺酰基团的二价基团，以及 Y代表由Y-OH所代表的化合物残基，包括含有醇羟基的醇羟基化合物残基，其中所述的Y-OH是一种喜树碱、紫杉醇或抗癌核苷酸）。
• NOVEL ANTICANCER CONCOMITANT DRUG
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1925309A1

  公开（公告）日：2008-05-28

  A cancer therapeutic agent according to the present invention comprises a combination of compound A described below, or a pharmaceutically acceptable salt thereof, and compound B described below, or a pharmaceutically acceptable salt thereof: Compound A: compound A1 represented by formula (1) below, or water-soluble prodrug A2 thereof; Compound B: at least one type of compound selected from the group consisting of a platinum-type anticancer compound, a gemcitabine-type compound, a 5-FU-type compound, a taxane-type compound, a vinca alkaloid-type compound, an anticancer tyrosine kinase inhibitor compound, and an anticancer monoclonal antibody; (wherein, R11 represents a hydrogen atom, a halogen atom or a C1-C6 alkyl group; R12 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, or a hydroxyl group; R21 represents a hydrogen atom or a C1-C10 alkyl group which may comprise one to three substituents selected from Group B described below: Group B: a C1-C6 alkoxy group, a hydroxy group, a halogen atom, an amino group, a mono-C1-C6 alkylamino group, a di-C1-C6 alkylamino group, a C3-C7 cycloalkyl group, a heterocycle, and an aryl ring (the aryl ring may comprise one to three substituents selected from the group consisting of a hydroxy group, a C1-C6 alkoxy group, a halogen atom, an amino group, a mono-C1-C6 alkylamino group, and a di-C1-C6 alkylamino group); and R22 represents a hydrogen atom, an amino group, or a C1-C6 alkyl group that may comprise one to three substituents selected from Group C described below, a C1-C6 alkoxy group that may comprise one to three substituents selected from Group C described below, a C1-C6 alkylthio group that may comprise one to three substituents selected from Group C described below, a mono-C1-C6 alkylamino group that may comprise one to three substituents selected from Group C described below, or a di-C1-C6 alkylamino group that may comprise one to three substituents selected from Group C described below: Group C: a C1-C6 alkoxy group, a hydroxy group, a halogen atom, an amino group, a C3-C7 cycloalkyl group, a heterocycle, and an aryl ring (the aryl ring may comprise one to three substituents selected from the group consisting of a hydroxy group, a C1-C6 alkoxy group, an amino group, a mono-C1-C6 alkylamino group, and a di-C1-C6 alkylamino group).

  根据本发明，一种癌症治疗剂包括以下所述的化合物A的组合物，或其药用可接受的盐，以及以下所述的化合物B的组合物，或其药用可接受的盐：化合物A：以下式（1）表示的化合物A1，或其水溶性前药A2；化合物B：选自铂类抗癌化合物、吉西他滨类化合物、5-氟尿嘧啶类化合物、紫杉醇类化合物、长春碱类化合物、抗癌酪氨酸激酶抑制剂化合物和抗癌单克隆抗体的化合物中的至少一种化合物；（其中，R11代表氢原子、卤原子或C1-C6烷基；R12代表氢原子、卤原子、C1-C6烷基或羟基；R21代表氢原子或C1-C10烷基，可能包括来自下文所述的B组的1至3个取代基：B组：C1-C6烷氧基、羟基、卤原子、氨基、单烷基氨基、双烷基氨基、C3-C7环烷基、杂环和芳基（芳基可能包括来自羟基、C1-C6烷氧基、卤原子、氨基、单烷基氨基和双烷基氨基的1至3个取代基）；R22代表氢原子、氨基或可能包括来自下文所述的C组的1至3个取代基的C1-C6烷基、可能包括来自下文所述的C组的1至3个取代基的C1-C6烷氧基、可能包括来自下文所述的C组的1至3个取代基的C1-C6烷硫基、可能包括来自下文所述的C组的1至3个取代基的单烷基氨基，或可能包括来自下文所述的C组的1至3个取代基的双烷基氨基：C组：C1-C6烷氧基、羟基、卤原子、氨基、C3-C7环烷基、杂环和芳基（芳基可能包括来自羟基、C1-C6烷氧基、氨基、单烷基氨基和双烷基氨基的1至3个取代基）。
• Novel hexacyclic compounds
  申请人：——

  公开号：US20030144304A1

  公开（公告）日：2003-07-31

  The present invention relates to hexacyclic compound of the formula [1], 1 wherein Z, R 3 and R 4 are as identified therein, and pharmaceutically acceptable salts thereof. These compounds are useful in the treatment of cell proliferative disorders.

  本发明涉及公式［1］中的六环化合物，其中Z、R3和R4如所述，以及其药用可接受的盐。这些化合物可用于治疗细胞增殖性疾病。
• Method for identifying an enzyme to design anti-cancer compounds
  申请人：——

  公开号：US20030138864A1

  公开（公告）日：2003-07-24

  The present invention relates to a method for identification of enzymes that are preferentially expressed in certain tumor tissue as compared with rapidly growing normal cells or tissue, use of said enzymes for the compound design to generate an active anti-cancer substance selectively in tumor tissue, compounds designed based on said enzymes, their pharmaceutically acceptable salts as well as pharmaceutical composition thereof.

  本发明涉及一种酶的鉴定方法，该酶在某些肿瘤组织中与快速生长的正常细胞或组织相比表达优势，利用该酶设计化合物以在肿瘤组织中选择性地生成活性抗癌物质，基于该酶设计的化合物、其药学上可接受的盐以及药物组成物。
• Novel Water-Soluble Prodrugs
  申请人：Umeda Isao

  公开号：US20080015157A1

  公开（公告）日：2008-01-17

  An objective of the present invention is to provide water-soluble prodrugs that can be administered parenterally, and which show excellent water solubility and small interspecies or individual differences and are rapidly converted to the active form by chemical conversion. This invention provides water-soluble prodrugs represented by formula (1), or pharmaceutically acceptable salts, or hydrates or solvates thereof, (wherein, R 1 represents a hydrogen atom, or C1-C6 alkyl group; W represents a divalent group comprising a tertiary amino group or sulfonyl group; and Y represents a residue of a compound represented by Y—OH comprising an alcoholic hydroxyl group).

  本发明的目的是提供可经由肌肉注射给药的水溶性前药，其具有优异的水溶性、小的种间或个体差异，并且可通过化学转化迅速转化为活性形式。本发明提供了由式(1)表示的水溶性前药，或其药学上可接受的盐、水合物或溶剂化物，其中R1代表氢原子或C1-C6烷基；W代表包含三级胺基或磺酰基的二价基团；Y代表由Y-OH表示的化合物的残基，该化合物包括醇羟基。