2-bromo-3-(bromomethyl)-6-methoxyquinoline

• 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: 2-bromo-3-(bromomethyl)-6-methoxyquinoline
• 英文别名: 2-bromo-3-bromomethyl-6-methoxyquinoline
• 化学式: C₁₁H₉Br₂NO
• 分子量: 331.007
• InChiKey: VSIUUBKHWAOYIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-bromo-3-(bromomethyl)-6-methoxyquinoline 在 氢溴酸 、 palladium diacetate 、 potassium carbonate 、 三苯基膦 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 22.0h， 生成 10-羟基喜树碱
  参考文献：
  名称：

  喜树碱和SN-38的全合成

  摘要：

  从廉价易得的材料开始，描述了一种新的实用，简明的对映体喜树碱和SN-38的全合成（总收率14％，ee 99.9％和纯度99.9％）。在所有步骤中都实现了无柱色谱纯化的发展，这为喜树碱家族生物碱提供了经济的工业生产方法。

  DOI：

  10.1021/jo201974f

文献信息

• Synthesis of New Camptothecin Analogues with the E-Lactone Ring Replaced by α,β-Cyclohexenone
  作者：Valeriy A. Bacherikov、Tsong-Jen Tsai、Jang-Yang Chang、Ting-Chao Chou、Rong-Zau Lee、Tsann-Long Su

  DOI：10.1002/ejoc.200600298

  日期：2006.10

  The total synthesis of racemic camptothecin analogues 12a and 12b, in which the E-lactone ring has been replaced by an α,β-cyclohexenone ring and the ethyl and hydroxy substituents have been retained, was achieved by first preparing the ABCD fragments 31a and 31b, which were then converted into the tetracyclic triol 36a and 36b by osmium-mediated dihydroxylation. Compounds 36a and 36b were oxidized

  外消旋喜树碱类似物 12a 和 12b 的全合成是通过首先制备 ABCD 片段 31a 和 31b 来实现的，其中 E-内酯环已被 α,β-环己烯酮环取代并且保留了乙基和羟基取代基，然后通过锇介导的二羟基化将其转化为四环三醇 36a 和 36b。化合物 36a 和 36b 在一锅反应中被氧化，然后分子内羟醛缩合得到所需的五环化合物 12a 和 12b，它们保留了拓扑异构酶 I 抑制活性，并对培养中的肿瘤细胞生长表现出细胞毒性。（© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
• Synthesis and pharmacological evaluation of novel non-lactone analogues of camptothecin
  作者：Patrick Hautefaye、Bernard Cimetière、Alain Pierré、Stéphane Léonce、John Hickman、William Laine、Christian Bailly、Gilbert Lavielle

  DOI：10.1016/s0960-894x(03)00534-1

  日期：2003.8

  Ten novel camptothecin (CPT) derivatives devoid of the lactone function in the E-ring were synthesized and evaluated as anticancer agents. Several of these CPT analogues bearing a five-membered E-ring are potent inhibitors of the DNA relaxation and cleavage reactions catalyzed by topoisomerase I and exhibit promising cytotoxic activities with IC(50) values in the nM range. This is the first successful

  合成了十个在E环中没有内酯功能的新型喜树碱（CPT）衍生物，并将其评估为抗癌剂。这些带有五元E环的CPT类似物中的几种是拓扑异构酶I催化的DNA松弛和裂解反应的有效抑制剂，并显示出有希望的细胞毒活性，其IC（50）值在nM范围内。这是无内酯的CPT的第一个成功设计，因此为拓扑异构酶I靶向抗肿瘤药的开发提供了新途径。
• CAMPTOTHECIN COMPOUND CONTAINING STABLE 7-MEMBERED LACTONE RING, PREPARATION METHOD AND USE
  申请人：East China Normal University

  公开号：EP2700642A1

  公开（公告）日：2014-02-26

  Provided are a camptothecin compound containing 7-membered lactone ring, as shown in general formula I, and pharmaceutically acceptable salt thereof, as well as the preparation method and use thereof. In general formula I, R1 is H, a C1∼C3 alkyl, acetyl or propionyl; R2 is H, a C1∼C6 alkyl, a C3~C6 cycloalkyl, piperidyl; or a C1∼C6 alkyl substituted by an amino; R3 is H, a C1∼C3 alkyl, or a C1∼C6 alkyl substituted by an amino; R4 is H, a hydroxyl, or a C1∼C6 alkoxy; R5 is H, or a C1∼C6 alkoxyl; or R4 and R5 are linked to each other to form -OCH2O- or -OCH2CH2O-. The compound has good anti-tumor activity, and can be clinically used via oral administration, intravenous injection, and intramuscular injection, among others.

  提供一种含有7元环内酯环的喜树碱化合物，如通式I所示，以及其药学上可接受的盐、制备方法和用途。在通式I中，R1为H、C1∼C3烷基、乙酰基或丙酰基；R2为H、C1∼C6烷基、C3~C6环烷基、哌啶基；或被氨基取代的C1∼C6烷基；R3为H、C1∼C3烷基或被氨基取代的C1∼C6烷基；R4为H、羟基或C1∼C6烷氧基；R5为H或C1∼C6烷氧基；或R4和R5相连形成-OCH2O-或-OCH2CH2O-。该化合物具有良好的抗肿瘤活性，可通过口服、静脉注射、肌肉注射等途径在临床上使用。
• New camptothecin analogue compounds
  申请人：——

  公开号：US20020077325A1

  公开（公告）日：2002-06-20

  Compound of formula (I): 1 wherein: n is 0, 1 or 2, R 1 , R 2 , R 3 , R 4 and R 5 are selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, perhaloalkyl, cycloalkyl, cycloalkylalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, acyloxy, carboxy, nitro, cyano, aminocarbonyl (optionally substituted), and the groups (CH 2 ) p —NR a R b and —O—C(O)—N—R a R b , with p, R a and R b being as defined in the description, or two adjacent groups R 2 , R 3 , R 4 and R 5 together form a group —O—(CH 2 ) t —O, t being an integer from 1 to 3), R 60 , R 70n , R 80 and R 90 represent a hydrogen atom, a hydroxy group, an alkoxy group, or an O—(CO)—X or O—(CO)—NXW group as defined in the description, R 61 , R 71n , R 81 and R 91 represent a hydrogen atom , alkyl, alkenyl or alkynyl, or taken in pairs together form a bond or an oxirane group, or two groups together form an oxo group. and medicinal products containing the same are useful for the treatment of cancerous diseases.

  化合物的式子（I）：其中：n为0、1或2，R1、R2、R3、R4和R5选择自氢、卤素、烷基、烯基、炔基、全氟烷基、环烷基、环烷基烷基、羟基、羟基烷基、烷氧基、烷氧基烷基、烷氧羰基、酰氧基、羧基、硝基、氰基、氨基羰基（可选择性取代），以及(CH2)p-NRaRb和-O-C(O)-N-RaRb这些基团，其中p、Ra和Rb如描述中所定义，或者相邻的两个基团R2、R3、R4和R5共同形成一个-O-( )t-O的基团，其中t为1到3的整数。R60、R70n、R80和R90代表氢原子、羟基、烷氧基或描述中定义的O-(CO)-X或O-(CO)-NXW基团。R61、R71n、R81和R91代表氢原子、烷基、烯基或炔基，或者成对地共同形成键或环氧丙烷基团，或者两个基团共同形成一个羰基团。含有这些化合物的药品对于治疗癌症疾病是有用的。
• New campothecin analogue compounds
  申请人：——

  公开号：US20030105109A1

  公开（公告）日：2003-06-05

  Compound of formula (I): 1 wherein: n is 0, 1 or 2, R 1 represents (C 3 -C 11 )cycloalkyl or (C 3 -C 11 )cycloalkylalkyl, R 2 , R 3 , R 4 and R 5 are selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, perhaloalkyl, cycloalkyl, cycloalkylalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, acyloxy, carboxy, nitro, cyano, aminocarbonyl (optionally substituted), and the groups (CH 2 ) p —N a R b and —O—C(O)—N—R a R b , with p, R a and R b being as defined in the description, or two adjacent groups R 2 , R 3 , R 4 and R 5 together form a group —O—(CH 2 ) t —O, t being an integer from 1 to 3, R 60 , R 70n , R 80 and R 90 represent a hydrogen atom, a hydroxy group, an alkoxy group, or an O—(CO)—X or O—(CO)—NXW group as defined in the description, R 61 , R 71n , R 81 , and R 91 represent a hydrogen atom, alkyl, alkenyl or alkynyl, or taken in pairs together form a bond or an oxirane group, or two groups together form an oxo group. and medicinal products containing the same are useful for the treatment of cancerous disesases.

  式(I)的化合物： 其中： n为0、1或2， R1代表(C3-C11)环烷基或(C3-C11)环烷基烷基， R2、R3、R4和R5选择自氢、卤素、烷基、烯基、炔基、全卤烷基、环烷基、环烷基烷基、羟基、羟基烷基、烷氧基、烷氧基烷基、烷氧羰基、酰氧基、羧基、硝基、氰基、氨基羰基（可选地取代）和(CH2)p—NaRb和—O—C(O)—N—RaRb基团，其中p、Ra和Rb如描述中定义，或者相邻的两个基团R2、R3、R4和R5组成—O—( )t—O基团，其中t为1到3的整数， R60、R70n、R80和R90代表氢原子、羟基、烷氧基，或者如描述中所定义的O—(CO)—X或O—(CO)—NXW基团， R61、R71n、R81和R91代表氢原子、烷基、烯基或炔基，或成对地共同形成键或环氧基团，或两个基团共同形成氧基团。 含有该化合物的药物对治疗癌症有用。