2-hydroxy-7-(3,4,5-trimethoxyphenyl)-7,11-dihydrobenzo[h]furo[3,4-b]quinolin-8(10H)-one

• 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-hydroxy-7-(3,4,5-trimethoxyphenyl)-7,11-dihydrobenzo[h]furo[3,4-b]quinolin-8(10H)-one
• 英文别名: 4-Hydroxy-11-(3,4,5-trimethoxyphenyl)-14-oxa-17-azatetracyclo[8.7.0.02,7.012,16]heptadeca-1(10),2(7),3,5,8,12(16)-hexaen-13-one
• 化学式: C₂₄H₂₁NO₆
• 分子量: 419.434
• InChiKey: BGZSCCWDIOJNJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  86.2
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-羟乙酰乙酸内酯 、 1-氨基-7-萘酚 、 3,4,5-三甲氧基苯甲醛 以 乙醇 为溶剂， 以63%的产率得到2-hydroxy-7-(3,4,5-trimethoxyphenyl)-7,11-dihydrobenzo[h]furo[3,4-b]quinolin-8(10H)-one
  参考文献：
  名称：

  Anticancer Properties of an Important Drug Lead Podophyllotoxin Can Be Efficiently Mimicked by Diverse Heterocyclic Scaffolds Accessible via One-Step Synthesis

  摘要：

  Structural simplification of an antimitotic natural product podophyllotoxin with mimetic heterocyclic scaffolds constructed using multicomponent reactions led to the identification of compounds exhibiting low nanomolar antiproliferative and apoptosis-inducing properties. The most potent compounds were found in the dihydropyridopyrazole, dihydropyridonaphthalene, dihydropyridoindole, and dihydropyridopyrimidine scaffold series. Biochemical mechanistic studies, performed with dihydropyridopyrazole compounds showed that these heterocycles inhibit in vitro tubulin polymerization and disrupt the formation of mitotic spindles in dividing cells at low nanomolar concentrations, in a manner similar to podophyllotoxin itself. Separation of a racemic dihydropyridonaphthalene into individual enantiomers demonstrated that only the optical antipode matching the absolute configuration of podophyllotoxin possessed potent anticancer activity. Computer modeling, performed using the podophyllotoxin binding site on P-tubulin, provided a theoretical understanding of these successful experimental findings.

  DOI：

  10.1021/jm200410r

文献信息

• Novel tricyclic dihydro-quinoline derivatives, method for preparing same and pharmaceutical compositions containing the same
  申请人：——

  公开号：US20040180917A1

  公开（公告）日：2004-09-16

  A compound of formula (I): 1 wherein: 2 represents a single or double bond, 3 represents a ring system selected from 4 5 R 9a , R 9b , R 9c , X and Y are as defined in the description, R 1 represents a group selected from hydrogen, aryl, heteroaryl, cycloalkyl, optionally substituted alkyl, and COR 11 , wherein R 11 is as defined in the description, R 2 to R 8 each represent a group selected from hydrogen, halogen, hydroxy, polyhaloalkyl, nitro, optionally substituted alkyl, optionally substituted amino, optionally substituted alkoxy, —OPO(OH) 2 and 6 wherein m represents an integer such that 1≦m<4, or R 2 with R 3 , or R 3 with R 4 , or R 4 with R 5 , form, together with the carbon atoms carrying them, an optionally substituted, mono- or bi-cyclic group optionally containing 1 or 2 hetero atoms, R 16 represents a hydrogen atom or an alkyl group, 7 represents an aryl, heteroaryl or aryl-alkyl group, its optical isomers, addition salts thereof with a pharmaceutically acceptable acid or base, and hydrates and solvates thereof.

  化合物的化学式（I）：其中：表示单键或双键，表示选自R9a、R9b、R9c的环系统，X和Y的定义如描述中所述，R1表示选自氢、芳基、杂环芳基、环烷基、可选择取代烷基和COR11的基团，其中R11的定义如描述中所述，R2至R8分别表示选自氢、卤素、羟基、多卤代烷基、硝基、可选择取代烷基、可选择取代氨基、可选择取代烷氧基、—OPO(OH)2的基团，其中m表示整数，使得1≤m<4，或R2与R3、或R3与R4、或R4与R5形成一个可选择取代的、含有1或2个杂原子的单环或双环基团，R16表示氢原子或烷基，表示芳基、杂环芳基或芳基烷基，其光学异构体，与药用可接受酸或碱形成的加合物盐，以及其水合物和溶剂合物。
• DERIVES TRICYCLIQUES DE DIHYDROQUINOLEINES,LEUR PROCEDE DE PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT
  申请人：LES LABORATOIRES SERVIER

  公开号：EP1399455A2

  公开（公告）日：2004-03-24
• [EN] NOVEL TRICYCLIC DIHYDRO-QUINOLINE DERIVATIVES, METHOD FOR PREPARING SAME AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME<br/>[FR] NOUVEAUX DERIVES TRICYCLIQUES DE DIHYDRO-QUINOLEINES, LEUR PROCEDE DE PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT
  申请人：SERVIER LAB

  公开号：WO2002094840A2

  公开（公告）日：2002-11-28

  Composé de formule (I): dans laquelle: représente une liaison simple ou double, représente un cycle choisi parmi - R9a,R9b,R9c, X et Y sont tels que définis dans la description, R1 représente un groupement choisi parmi hydrogène, aryle, hétéroaryle, cycloalkyle, alkyle éventuellement substitué, et COR11 dans lequel R11 est tel que défini dans la description, R2 à R8 représentent chacun un groupement choisi parmi hydrogène, halogène, hydroxy, polyhalogénoalkyle, nitro, alkyle éventuellement substitué, amino éventuellement substitué, alkoxy éventuellement substitué, -OPO(OH)2 et dans laquelle m représente un entier tel que 1≤m≤4, ou R2 avec R3, ou R3 avec R4, ou R4 avec R5, forment ensemble avec les atomes de carbone qui les portent un groupement mono- ou bicyclique contenant éventuellement 1 ou 2 hétéroatomes et éventuellement substitué, R16 représente un atome d'hydrogène ou un groupement alkyle, représente un groupement aryle, hétéroaryle ou arylalkyle, ses isomères optiques, ses sels d'addition à un acide ou à une base pharmaceutiquement acceptable ainsi que ses hydrates et solvates. Médicaments.
• Anticancer Properties of an Important Drug Lead Podophyllotoxin Can Be Efficiently Mimicked by Diverse Heterocyclic Scaffolds Accessible via One-Step Synthesis
  作者：Igor V. Magedov、Liliya Frolova、Madhuri Manpadi、Uma devi Bhoga、Hong Tang、Nikolai M. Evdokimov、Olivia George、Kathy Hadje Georgiou、Steffen Renner、Matthäus Getlik、Tiffany L. Kinnibrugh、Manuel A. Fernandes、Severine Van slambrouck、Wim F. A. Steelant、Charles B. Shuster、Snezna Rogelj、Willem A. L. van Otterlo、Alexander Kornienko

  DOI：10.1021/jm200410r

  日期：2011.6.23

  Structural simplification of an antimitotic natural product podophyllotoxin with mimetic heterocyclic scaffolds constructed using multicomponent reactions led to the identification of compounds exhibiting low nanomolar antiproliferative and apoptosis-inducing properties. The most potent compounds were found in the dihydropyridopyrazole, dihydropyridonaphthalene, dihydropyridoindole, and dihydropyridopyrimidine scaffold series. Biochemical mechanistic studies, performed with dihydropyridopyrazole compounds showed that these heterocycles inhibit in vitro tubulin polymerization and disrupt the formation of mitotic spindles in dividing cells at low nanomolar concentrations, in a manner similar to podophyllotoxin itself. Separation of a racemic dihydropyridonaphthalene into individual enantiomers demonstrated that only the optical antipode matching the absolute configuration of podophyllotoxin possessed potent anticancer activity. Computer modeling, performed using the podophyllotoxin binding site on P-tubulin, provided a theoretical understanding of these successful experimental findings.