二乙基[[3,4-(亚甲二氧基)苯胺基]亚甲基]丙二酸酯 | 17394-77-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 中文名称: 二乙基[[3,4-(亚甲二氧基)苯胺基]亚甲基]丙二酸酯
• 英文名称: diethyl 3,4-methylenedioxyanilinomethylene malonate
• 英文别名: diethyl [[3,4-(methylenedioxy)phenylamino]methylene]malonate；NSC332161；benzo[1,3]dioxol-5-ylaminomethylene-malonic acid diethyl ester；Propanedioic acid, [(1,3-benzodioxol-5-ylamino)methylene]-, diethyl ester；diethyl 2-[(1,3-benzodioxol-5-ylamino)methylidene]propanedioate
• CAS: 17394-77-3
• 化学式: C₁₅H₁₇NO₆
• 分子量: 307.303
• InChiKey: XQBHPGINZRUJMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  二乙基[[3,4-(亚甲二氧基)苯胺基]亚甲基]丙二酸酯 在 ammonium hydroxide 作用下， 以 methyloxirane 、 水 为溶剂， 反应 2.0h， 以80%的产率得到8-羟基[1,3]二氧代lo[4,5-g]喹啉-7-羧酸乙酯
  参考文献：
  名称：

  [EN] METHODS FOR TREATING HEMATOLOGICAL MALIGNANCIES
  [FR] MÉTHODES DE TRAITEMENT DE MALIGNITÉS HÉMATOLOGIQUES

  摘要：

  这项发明提供了治疗特定血液系统癌症的方法和药物组合物。

  公开号：

  WO2012015875A1
• 作为产物：
  描述：

  丙二酸二乙酯 在 乙酸酐 、 zinc(II) chloride 作用下， 以 苯 为溶剂， 反应 7.0h， 生成 二乙基[[3,4-(亚甲二氧基)苯胺基]亚甲基]丙二酸酯
  参考文献：
  名称：

  设计，合成和双重评估喹啉和喹啉碘化物盐衍生物作为潜在的抗癌和抗菌剂。

  摘要：

  设计并合成了一系列新型的喹啉和碘化喹啉鎓衍生物，以发现潜在的抗癌和抗菌剂。关于抗癌特性，评估了对三种人类癌细胞系（A-549，HeLa和SGC-7901）的体外细胞毒性。评估了对两种菌株大肠杆菌（ATCC 29213）和金黄色葡萄球菌（ATCC 8739）的抗菌性能，以及最低抑菌浓度（MIC）值。目标烷基碘取代的化合物表现出显着的抗肿瘤和抗菌活性，其中化合物8-（（4-（苄氧基）苯基）氨基）-7-（乙氧羰基）-5-丙基-[1,3] dioxolo [4,5- g]喹啉-5-鎓（12）被发现是对A-549，HeLa，SGC-7901，IC50值分别为4.45±0.88、4.74±0.42、14.54±1.96和32.12±3.66的最有效衍生物。和L-02细胞分别强于阳性对照5-FU和MTX。此外，化合物12具有最有效的细菌抑制活性。该化合物对大肠杆菌和金黄色葡萄球菌的MIC为3.125 n

  DOI：

  10.1002/cmdc.202000002

文献信息

• Optimization of activity localization of quinoline derivatives: Design, synthesis, and dual evaluation of biological activity for potential antitumor and antibacterial agents
  作者：Guofan Jin、Zhenwang Li、Fuyan Xiao、Xueyong Qi、Xianyu Sun

  DOI：10.1016/j.bioorg.2020.103837

  日期：2020.6

  strains, Escherichia coli (ATCC 29213) and Staphylococcus aureus (ATCC 8739), along with minimum inhibitory concentration (MIC) values were evaluated. The target compounds, 5-12, exhibited significant antitumor and antibacterial activity, of which compound 12 was found to be the most potent derivative with IC50 values of 5.18 ± 0.64, 7.62 ± 1.05, 17.59 ± 0.41, and 54.45 ± 4.88 against A-549, Hela, SGC-7901

  从丙二酸酯和苯并[d] [1,3]二氧杂-5-胺开始，分几步以中等收率制备了碘化喹啉与偶数烷基链结合的新型季胺。所有活性结构化合物均通过核磁共振（NMR）进行了鉴定，例如1H NMR，13C NMR，红外辐射（IR），高分辨率质谱（HR-MS）和Carlo Erba Instruments CHNS-O EA1108光谱分析。关于抗癌特性，评估了对三种人类癌细胞系（A-549，Hela和SGC-7901）的体外细胞毒性。评估了对两种人类细菌菌株大肠杆菌（ATCC 29213）和金黄色葡萄球菌（ATCC 8739）的抗菌性能，以及最低抑菌浓度（MIC）值。目标化合物5-12 表现出显着的抗肿瘤和抗菌活性，其中化合物12被发现是最有效的衍生物，针对A-549，Hela，SGC-7901的IC50值为5.18±0.64、7.62±1.05、17.59±0.41和54.45±4.88。和L-02细
• Substituted quinolines as antitumor agents
  申请人：Boyle Thomas Francis

  公开号：US20070021407A1

  公开（公告）日：2007-01-25

  The invention provides a compound of Formula (Ia), or a pharmaceutically acceptable salt, pro-drug or solvate thereof. wherein: n is 0 or 1; Y is selected from —NH—, —O—, —S—, or —NR 7 — where R 7 is alkyl of 1-6 carbon atoms; R 5 is cyano, fluoro, chloro or bromo; R 6 is cycloalkyl of 3 to 7 carbon atoms, which may be optionally substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a pyridinyl, pyrimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- di-, or tri-substituted; or R 6 is a group —R 8 —X—R 9 where R 8 is a divalent cycloalkyl of 3 to 7 carbon atoms, which may be optionally further substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a divalent pyridinyl, pyimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally further substituted with one or more groups; and where X is selected from —NH—, —O—, —S—, CH 2 or —NR 7′ — where R 7′ is alkyl of 1-6 carbon atoms, and R 9 is a group (CH 2 ) m R 10 where m is 0, or an integer of from 1-3 and R 10 is an optionally substituted aryl or optionally substituted cycloalkyl ring of up to 10 carbon atoms, or R 10 is a optionally substituted heterocyclic ring or an N-oxide of any nitrogen containing ring; R 1 , R 2 , R 4 are independently selected from hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C 1-3 alkyl, —NR 11 R 12 — (wherein R 11 and R 12 , which may be the same or different each represents hydrogen, or C 1-3 alkyl), or a group R 13 —X 1 —(CH 2 ) x wherein x is 0 or an integer of from 1 to 3, X 1 represents a direct bond, —O—, —CH 2 —, —OC(O)—, —C(O)—, —S—, —SO—, —SO 2 —, —NR 14 C(O)—, —NR 14 C(O)O—, —C(O)NR 15 —, —C(O)ONR 15 —, —SO 2 NR 16 —, —NR 17 SO 2 — —NR 18 — or —NR 18 NR 18 — (wherein R 14 , R 15 , R 16 , R 17 and R 18 each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl)), and R 13 is hydrogen, optionally substituted hydrocarbyl, or optionally substituted heterocyclyl; and R 3 is selected from (i) a group of formula —X 1 —R x —(OH) p where X 1 is as defined above, R x is an alkylene, alkenylene or alkynylene chain, optionally interposed with a heteroatom or a heteocyclic ring and p is 1 or 2; (ii) a group of formula R 13a —(CH 2 ) y —X 1 —(CH 2 ) x where R 13 a is as defined for R 13 above, and X 1 and x are as defined above, y is 0 or an integer between 1 and 5, wherein (CH 2 ) y is optionally interposed by an X 1 group; (iii) a group of formula —X 1 —R y —NR z —R y′ —S—R y″ where X 1 is as defined above, R y , R y′ and R y″ are independently selected from alkyl, alkenyl or alkynyl chains, and R z is hydrogen or alkyl, or R z and R y″ are joined together to form an optionally substituted nitrogen and sulphur containing ring; (iv) a group of formula —X 1 —R x′ —(C 3-6 cycloalkyl) where X 1 is as defined above and R x′ is an alkylene, alkenylene or alkynylene chain, optionally interposed with a heteroatom a group of the formula —X 1 —C 1-5 alkyl where X 1 is as defined above and C 1-5 alkyl is substituted by one more substituents independently selected from chloro and cyano; (v) a group of the formula —X 1 —C 1-3 alkyl-CO—NR 18 NR 18 —R 20 where R 18 is as defined above and R 20 is selected from hydrogen or C 1-5 alkoxycarbonyl; or (vi) a heterocyclic ring. The invention also provides a process for the preparation of a compound of Formula (Ia), pharmaceutical compositions of a compound of Formula (Ia) and methods for the treatment or prevention of cancer comprising administering an effective amount of a compound of Formula (1a).

  本发明提供了公式（Ia）的化合物，或其药学上可接受的盐，前药或溶剂化物。其中：n为0或1；Y选自—NH—，—O—，—S—或—NR7—，其中R7为1-6个碳原子的烷基；R5为氰基，氟基，氯基或溴基；R6为3-7个碳原子的环烷基，可以选择地用1-6个碳原子的烷基取代；或为吡啶基，嘧啶基或苯基环；其中吡啶基，嘧啶基或苯基环可以选择性地单取代，二取代或三取代；或R6为—R8—X—R9的基团，其中R8为3-7个碳原子的二价环烷基，可以选择地进一步用1-6个碳原子的烷基取代；或为二价的吡啶基，嘧啶基或苯基环；其中吡啶基，嘧啶基或苯基环可以选择性地进一步用一个或多个基团取代；X选自—NH—，—O—，—S—，CH2或—NR7′—，其中R7′为1-6个碳原子的烷基，R9为( )mR10的基团，其中m为0或1-3的整数，R10为最多有10个碳原子的可选择性取代芳基或可选择性取代的环烷基环，或R10为可选择性取代的杂环环或任何含氮环的N-氧化物；R1，R2，R4独立选择自氢，羟基，卤基，氰基，硝基，三氟甲基，C1-3烷基，—NR11R12—（其中R11和R12，可以相同或不同，每个表示氢或C1-3烷基），或R13—X1—（ ）x的基团，其中x为0或1-3的整数，X1表示直接键，—O—，— —，—OC（O）—，—C（O）—，—S—，—SO—，—SO2—，—NR14C（O）—，—NR14C（O）O—，—C（O）NR15—，—C（O）ONR15—，—SO2NR16—，—NR17SO2—，—NR18—或—NR18NR18—（其中R14，R15，R16，R17和R18各自独立表示氢，C1-3烷基或C1-3烷氧基C2-3烷基），R13为氢，可选择性取代的碳氢基或可选择性取代的杂环基；R3选自（i）公式—X1—Rx—（OH）p的基团，其中X1，Rx和p如上所定义；（ii）公式R13a—（ ）y—X1—（ ）x的基团，其中R13a如上所定义，X1和x如上所定义，y为0或1-5之间的整数，其中（ ）y可以选择性地由X1基团插入；（iii）公式—X1—Ry—NRz—Ry′—S—Ry″的基团，其中X1，Ry，Ry′和Ry″各自独立选择自烷基，烯基或炔基链，Rz为氢或烷基，或Rz和Ry″结合形成可选择性取代的氮和硫含有环；（iv）公式—X1—Rx′—（C3-6环烷基）的基团，其中X1和Rx′如上所定义，可以选择性地插入一个杂原子；公式—X1—C1-5烷基的基团，其中X1如上所定义，C1-5烷基被一个或多个独立选择自氯和氰基的取代基取代；（v）公式—X1—C1-3烷基-CO—NR18NR18—R20的基团，其中R18和R20如上所定义；或（vi）杂环环。本发明还提供了公式（Ia）的化合物的制备方法，公式（Ia）的药物组合物以及使用公式（1a）的化合物的治疗或预防癌症的方法。
• 4-Substituted quinolines as antitumor agents
  申请人：Boyle Thomas Francis

  公开号：US20080027054A1

  公开（公告）日：2008-01-31

  The invention concerns compounds of formula (I), wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 , R 9 , R 10 m, n, p, X, Y and Z have any meanings defined in the description, processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an anti-proliferative agent in the treatment of solid tumour disease.

  该发明涉及式(I)的化合物，其中R1、R2、R3、R4、R5、R6、R8、R9、R10、m、n、p、X、Y和Z的任何含义定义在说明中，它们的制备方法，包含它们的制药组合物，以及在制造用于治疗实体肿瘤疾病的抗增殖剂药物时使用它们的用途。
• Structural development of a type-1 ryanodine receptor (RyR1) Ca2+-release channel inhibitor guided by endoplasmic reticulum Ca2+ assay
  作者：Shuichi Mori、Hiroto Iinuma、Noriaki Manaka、Mari Ishigami-Yuasa、Takashi Murayama、Yoshiaki Nishijima、Akiko Sakurai、Ryota Arai、Nagomi Kurebayashi、Takashi Sakurai、Hiroyuki Kagechika

  DOI：10.1016/j.ejmech.2019.06.076

  日期：2019.10

  Type-1 ryanodine receptor (RyRI) is a calcium-release channel localized on sarcoplasmic reticulum (SR) of the skeletal muscle, and mediates muscle contraction by releasing Ca2+ from the SR. Genetic mutations of RyRI are associated with skeletal muscle diseases such as malignant hyperthermia and central core diseases, in which over-activation of RyRI causes leakage of Ca2+ from the SR. We recently developed an efficient high-throughput screening system based on the measurement of Ca2+ in endoplasmic reticulum, and used it to identify oxolinic acid (1) as a novel RyRI channel inhibitor. Here, we designed and synthesized a series of quinolone derivatives based on 1 as a lead compound. Derivatives bearing a long alkyl chain at the nitrogen atom of the quinolone ring and having a suitable substituent at the 7-position of quinolone exhibited potent RyR1 channel-inhibitory activity. Among the synthesized compounds, 14h showed more potent activity than dantrolene, a known RyR1 inhibitor, and exhibited high RyR1 selectivity over RyR2 and RyR3. These compounds may be promising leads for clinically applicable RyRI channel inhibitors. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Gall-Istok, K.; Sterk, L.; Deak, Gy., Acta Chimica Hungarica, 1983, vol. 112, # 2, p. 241 - 252
  作者：Gall-Istok, K.、Sterk, L.、Deak, Gy.

  DOI：——

  日期：——