4-(methoxymethoxy)-4'-methoxybenzophenone | 115499-97-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(methoxymethoxy)-4'-methoxybenzophenone
• 英文别名: 4-methoxy-4'-methoxymethylbenzophenone；4-methoxy-4'-methoxymethoxybenzophenone；[4-(Methoxymethoxy)phenyl](4-methoxyphenyl)methanone；[4-(methoxymethoxy)phenyl]-(4-methoxyphenyl)methanone
• CAS: 115499-97-3
• 化学式: C₁₆H₁₆O₄
• 分子量: 272.301
• InChiKey: ZFDHCWBUWZVQLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(methoxymethoxy)-4'-methoxybenzophenone 在 盐酸 、 sodium hydroxide 、 正丁基锂 、 四甲基乙二胺 、 potassium tert-butylate 、 四丁基硫酸氢铵 、 三溴化硼 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 70.5h， 生成 阿非昔芬
  参考文献：
  名称：

  针对乳腺癌细胞的阿霉素-甲醛偶联物的设计，合成和生物学评估。

  摘要：

  蒽环类抗肿瘤药阿霉素（DOX）作为广谱化疗药物已使用了数十年。最近的文献证据表明甲醛在细胞毒性机理中的作用，蒽环甲醛-甲醛偶联物在体外和体内均具有显着增强的活性。将阿霉素-甲醛缀合物特异性靶向癌细胞可以提供更有效的化学疗法。报道了针对雌激素受体的阿霉素-甲醛缀合物的设计和11步合成，该缀合物通常在乳腺癌细胞中过表达。甲醛以掩蔽的形式掺入，作为阿霉素和水杨酰胺之间的N-曼尼希键。水杨酰胺触发分子，先前已开发出可释放阿霉素-甲醛活性代谢物的物质，通过衍生化的乙二醇将T 1束缚到4-羟基他莫昔芬的E和Z混合物中。选择靶向组E / Z-4-羟基他莫昔芬具有紧密结合雌激素受体和抗雌激素结合位点的能力。评估目标阿霉素-甲醛共轭物的雌激素受体结合和体外生长抑制作用，作为系链长度的函数。带有三甘醇链的先导化合物DOX-TEG-TAM以相对于E / Z-4-羟基他莫昔芬的2.5％的结合亲和力结合雌激素受体，

  DOI：

  10.1021/jm030352r
• 作为产物：
  描述：

  (4-羟基苯基)-(4-甲氧基苯基)甲酮 以95的产率得到4-(methoxymethoxy)-4'-methoxybenzophenone
  参考文献：
  名称：

  J. Med. Chem. 2004, 47, 1193-1206

  摘要：

  DOI：

文献信息

• Antiestrogen Binding Site and Estrogen Receptor Mediate Uptake and Distribution of 4-Hydroxytamoxifen-Targeted Doxorubicin−Formaldehyde Conjugate in Breast Cancer Cells
  作者：Patrick J. Burke、Brian T. Kalet、Tad H. Koch

  DOI：10.1021/jm049496b

  日期：2004.12.1

  de conjugates possess substantially enhanced activity in vitro and in vivo. We have recently reported the design, synthesis, and preliminary evaluation of a doxorubicin-formaldehyde conjugate targeted, via 4-hydroxytamoxifen, to the estrogen receptor (ER) and antiestrogen binding site (AEBS), which are commonly present in breast cancer cells. The lead targeted doxorubicin-formaldehyde conjugate, called

  蒽环类抗肿瘤药阿霉素（DOX）长期以来一直用作广谱化疗药物。现在，文献记录了甲醛在细胞毒性机制中的作用，蒽环甲醛-甲醛偶联物在体外和体内均具有显着增强的活性。我们最近报道了通过4-羟基他莫昔芬靶向于乳腺癌细胞中常见的雌激素受体（ER）和抗雌激素结合位点（AEBS）的阿霉素-甲醛缀合物的设计，合成和初步评估。发现相对于临床阿霉素和非靶向对照偶联物，尤其是在ER阴性，多药耐药的MCF-7 / Adr细胞中，铅靶向的阿霉素-甲醛偶联物称为DOX-TEG-TAM，具有优异的细胞生长抑制特性。在缺乏雌激素受体的情况下增强的活性增加了靶向也通过AEBS介导的可能性。ER阴性，AEBS阳性细胞系的荧光显微镜显示时间的函数，表明最初的DOX-TEG-TAM在细胞质中定位，这与最初的DOX和未靶向的阿霉素-甲醛共轭物在细胞核中的定位相反。DOX-TEG-TAM被四个AEBS阳性细胞系吸收的程度大于阿霉素和未
• Diphenyl-methane compounds useful in the treatment of diseases caused by
  申请人：Eisai Co., Ltd.

  公开号：US04886834A1

  公开（公告）日：1989-12-12

  A new diphenyl-methane derivative is useful to inhibit agglomeration of blood and is defined by the formula, including a diphenylethylene derivative and a benzophenone oxime ether derivative. ##STR1## in which R1 and R2 each are hydrogen, hydroxyl or a lower alkoxy, U is .dbd.CXY or .dbd.N--O--W, X is hydrogen, cyano or --COR6, R6 being hydroxyl or an amino, Y is --R10--COOR3, R3 being hydrogen or a lower alkoxy, R10 being an alkylene having 1 to 3 carbon atoms, straight or branched, --CO--NR4R5, R4 and R5 each being hydrogen, a lower alkyl or a lower arylalkyl, --CH2--NHSO2--C6H5 or --C(R8).dbd.NR7, R7 being a lower alkoxy or an aryl, R8 is --VR9, V being oxygen, sulfur or nitrogen, R9 being an alkyl or an aryl, W is --CH2--CO--CH2--COOR13, R13 being hydrogen or a lower alkyl, --CH2--C(C.dbd.NOR14)--CH2--COOR15, R15 being hydrogen or a lower alkyl, R14 being a lower alkyl, --CH(CN)--(CH2)q--COOR16, R16 being hydrogen or a lower alkyl, q being an integer of 1 to 3, or --(CH2)p--Z, Z being --SH, --SCN or a monovalent group derived from a five- or six-membered ring which may be substituted by a ring having one or more sulfur atoms in the ring, p being 1 or 2.

  一种新的二苯甲烷衍生物，用于抑制血液凝聚，其定义由以下化学式确定，包括二苯乙烯衍生物和苯甲酮肟醚衍生物。其中R1和R2分别为氢、羟基或较低的烷氧基，U为.dbd.CXY或.dbd.N--O--W，X为氢、氰基或--COR6，R6为羟基或氨基，Y为--R10--COOR3，R3为氢或较低的烷氧基，R10为1至3个碳原子的直链或支链烷基，--CO--NR4R5，R4和R5分别为氢、较低的烷基或较低的芳基烷基，--CH2--NHSO2--C6H5或--C(R8).dbd.NR7，R7为较低的烷氧基或芳基，R8为--VR9，V为氧、硫或氮，R9为烷基或芳基，W为--CH2--CO--CH2--COOR13，R13为氢或较低的烷基，--CH2--C(C.dbd.NOR14)--CH2--COOR15，R15为氢或较低的烷基，R14为较低的烷基，--CH(CN)--(CH2)q--COOR16，R16为氢或较低的烷基，q为1至3的整数，或--(CH2)p--Z，Z为--SH、--SCN或由五元或六元环衍生的一价基团，该环可能被一个或多个硫原子取代，p为1或2。
• Targeted Drug-Formaldehyde Conjugates and Methods of Making and Using the Same
  申请人：Koch H. Tad

  公开号：US20070275911A1

  公开（公告）日：2007-11-29

  The invention provides a prodrug platform technology for improving the therapeutic value of a variety of parent drug compounds by altering and improving drug characteristics such as aqueous solubility, hydrolytic stability, therapeutic index, toxicity profile, pharmacolcinetics and selectivity while allowing the potential for synthetic elaboration. The prodrug platform is particularly well suited for targeting therapeutic drugs, including anti-tumor drugs and antibiotics, to specific receptors on target cells (e.g., cancer cells and bacteria). The platform is a technology for providing an improved, preactivated form of a therapeutic drug, and for optionally targeting such drug to target cells or biological molecules. The invention is broadly applicable to many different therapeutic drugs, as well as to a variety of diseases and conditions, including a variety of forms of cancer and bacterial infections.

  本发明提供了一种前药平台技术，通过改变和改进药物特性，如水溶性、水解稳定性、治疗指数、毒性谱、药代动力学和选择性，从而提高各种原始药物化合物的治疗价值，同时允许潜在的合成扩展。该前药平台特别适用于将治疗药物，包括抗肿瘤药物和抗生素，定向靶向到目标细胞（例如癌细胞和细菌）上的特定受体。该平台是一种提供改进的、预激活形式的治疗药物的技术，并可选择性地将该药物定向到目标细胞或生物分子。本发明广泛适用于许多不同的治疗药物，以及多种癌症和细菌感染等不同疾病和病况。
• Benzophenone oxime derivatives, pharmaceutical compositions and use
  申请人：Eisai Co., Ltd.

  公开号：EP0478001A1

  公开（公告）日：1992-04-01

  A new diphenyl-methane derivative is useful to inhibit agglomeration of blood and is defined by the formula, including a diphenylethylene derivative and a benzophenone oxime ether derivative. in which R1 and R2 each are hydrogen, hydroxyl or a lower alkoxy, U is = CXY or = N-O-W, X is hydrogen, cyano or -COR6, R6 being hydroxyl or an amino, Y is -R10-COOR3, R3 being hydrogen or a lower alkoxy, R10 being an alkylene having 1 to 3 carbon atoms, straight or branched, -CO-NR4R5, R4 and R5 each being hydrogen, a lower alkyl or a lower arylalkyl, -CH2-NHS02-C6H5 or -C(R8)-= NR7, R7 being a lower alkoxy or an aryl, R8 is -VR9, V being oxygen, sulfur or nitrogen, R9 being an alkyl or an aryl, W is -CH2-CO-CH2-COOR13, R13 being hydrogen or a lower alkyl, -CH2-C(=NOR14)-CH2-COOR15, R15 being hydrogen or a lower alkyl, R14 being a lower alkyl, -CH(CN)-(CH2)q-COOR16, R16 being hydrogen or a lower alkyl, q being an integer of 1 to 3, or -(CH2)p-Z, Z being -SH, -SCN or a monovalent group derived from a five- or six-membered ring which may be substituted by a ring having one or more sulfur atoms in the ring, p being 1 or 2. A pharmaceutical composition containing compounds of formula (XX) or their pharmaceutically acceptable salts as active ingredients, and the use of compounds of formula (XX) or their pharmaceutically acceptable salts in the preparation of a medicament for treatment of diseases caused by blood stream disorders are also disclosed.

  一种新的二苯基甲烷衍生物可用于抑制血液凝集，其定义式包括一种二苯基乙烯衍生物和一种二苯甲酮肟醚衍生物。 其中 R1 和 R2 各为氢、羟基或低级烷氧基，U 为＝CXY 或＝N-O-W、 X是氢、氰基或-COR6，R6是羟基或氨基，Y是-R10-COR3，R3是氢或低级烷氧基，R10是具有 1 至 3 个碳原子的直链或支链亚烷基，-CO-NR4R5、R4和R5各自为氢、低级烷基或低级芳烷基，-CH2-NHS02-C6H5或-C(R8)-= NR7，R7为低级烷氧基或芳基，R8为-VR9，V为氧、硫或氮，R9为烷基或芳基、 W 是-CH2-CO-CH2-COOR13，R13 是氢或低级烷基，-CH2-C(=NOR14)-CH2-COOR15，R15 是氢或低级烷基，R14 是低级烷基，-CH(CN)-(CH2)q-COOR16，R16 是氢或低级烷基、q为 1 至 3 的整数，或-(CH2)p-Z，Z 为-SH、-SCN 或由五元环或六元环衍生的一价基团，该五元环或六元环可被环中具有一个或多个硫原子的环取代，p 为 1 或 2。 本发明还公开了一种含有式（XX）化合物或其药学上可接受的盐作为活性成分的药物组合物，以及式（XX）化合物或其药学上可接受的盐在制备治疗由血流紊乱引起的疾病的药物中的用途。
• [EN] TARGETED DRUG-FORMALDEHYDE CONJUGATES AND METHODS OF MAKING AND USING THE SAME<br/>[FR] CONJUGUES CIBLES MEDICAMENT-FORMALDEHYDE ET PROCEDES DE FABRICATION ASSOCIES
  申请人：UNIV COLORADO

  公开号：WO2005034856A3

  公开（公告）日：2005-08-11