4-(N-马来酰亚胺基甲基)环己基甲酸 | 69907-67-1

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 4-(N-马来酰亚胺基甲基)环己基甲酸
• 中文别名: 4-(马来酰亚胺甲基)环己烷羧酸
• 英文名称: 4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid
• 英文别名: 4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexane-1-carboxylic acid
• CAS: 69907-67-1；64987-82-2
• 化学式: C₁₂H₁₅NO₄
• 分子量: 237.255
• InChiKey: LQILVUYCDHSGEU-UHFFFAOYSA-N

物化性质

• 熔点：
  157-158°C
• 沸点：
  433.6±18.0 °C(Predicted)
• 密度：
  1.329±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2925190090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  4-(N-马来酰亚胺基甲基)环己基甲酸 在 N-羟基丁二酰亚胺 、 草酰氯 、 二甲基亚砜 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 27.33h， 生成 BMCA
  参考文献：
  名称：

  Comparison of Hydrazone Heterobifunctional Cross-Linking Agents for Reversible Conjugation of Thiol-Containing Chemistry

  摘要：

  Reversible covalent conjugation chemistries that allow site- and condition-specific coupling and uncoupling reactions are attractive components in nanotechnologies, bioconjugation methods, imaging, and drug delivery systems. Here, we compare three heterobifunctional cross-linkers, containing both thiol- and amine-reactive chemistries, to form pH-labile hydrazones with hydrazide derivatives of the known and often published water-soluble polymer, poly[N-(2-hydroxypropyl methacrylamide)] (pHPMA), while subsequently coupling thiol-containing molecules to the cross-linker via maleimide addition. Two novel cross-linkers were prepared from the popular heterobifunctional cross-linking agent, succinimidyl-4-(N-maleimidomethyl) cyclohexane-l-carboxylate (SMCC), modified to contain either terminal aldehyde groups (i.e., 1-(N-3-propanal)-4-(N-maleimidomethyl) cyclohexane carboxamide, PMCA) or methylketone groups (i.e., 1-(N-3-butanone)-4-(N-maleimidomethyl) cyclohexane carboxamide, BMCA). A third cross-linking agent was the commercially available N-4-acetylphenyl maleimide (APM). PMCA and BMCA exhibited excellent reactivity toward hydrazide-derivatized pHPMA with essentially complete hydrazone conjugation to polymer reactive sites, while APM coupled only similar to 60% of available reactive sites on the polymer despite a 3-fold molar excess relative to polymer hydrazide groups. All polymer hydrazone conjugates bearing these bifunctional agents were then further reacted with thiol-modified tetramethylrhodamine dye, confirming crosslinker maleimide reactivity after initial hydrazone polymer conjugation. Incubation of dye-labeled polymer conjugates in phosphate buffered saline at 37 degrees C showed that hydrazone coupling resulting from APM exhibited the greatest difference in stability between pH 7.4 and 5.0, with hydrolysis and dye release increased at pH 5.0 over a 24 h incubation period. Polymer conjugates bearing hydrazones formed from cross-linker BMCA exhibited intermediate stability with hydrolysis much greater at pH 5.0 at early time points, but hydrolysis at pH 7.4 was significant after 5 h. Hydrazones formed with the PMCA cross-linker showed no difference in release rates at pH 7.4 and 5.0.

  DOI：

  10.1021/bc100049c
• 作为产物：
  描述：

  凝血酸 以 溶剂黄146 、 甲苯 为溶剂， 反应 15.0h， 生成 4-(N-马来酰亚胺基甲基)环己基甲酸
  参考文献：
  名称：

  马来酰亚胺官能化的HPMA共聚物的合成以及aRAGE和人免疫球蛋白（huIgG）聚合物共轭物的体外表征。

  摘要：

  本文报道了基于聚合物HPMA的具有很窄分散性的抗体-聚合物结合物的合成。这些偶联物是通过将抗体与马来酰亚胺官能化的聚（N（2-羟丙基）-甲基丙烯酰胺）（poly-HPMA）共聚物是通过活化酯聚合物的中间步骤通过甲基丙烯酸五氟苯基酯的可逆加成-断裂链转移（RAFT）聚合而得到的。我们开发了一种协议，该协议允许连接两种不同的模型抗体，单克隆抗RAGE（晚期糖基化终产物的受体）抗体和多克隆人免疫球蛋白（huIgG）。通过SDS-PAGE电泳监测抗体的修饰和结合。Western Blott和细胞摄取分析证明了对免疫系统细胞的亲和力得以保持。

  DOI：

  10.1002/mabi.201200344

文献信息

• Cobalamin conjugates for anti-tumor therapy
  申请人：Weinshenker M. Ned

  公开号：US20050054607A1

  公开（公告）日：2005-03-10

  The present invention provides a cobalamin-drug conjugate suitable for the treatment of tumor related diseases. Cobalamin is indirectly covalently bound to an anti-tumor drug via a cleavable linker and one or more optional spacers. Cobalamin is covalently bound to a first spacer or the cleavable linker via the 5′-OH of the cobalamin ribose ring. The drug is bound to a second spacer of the cleavable linker via an existing or added functional group on the drug. After administration, the conjugate forms a complex with transcobalamin (any of its isoforms). The complex then binds to a receptor on a cell membrane and is taken up into the cell. Once in the cell, an intracellular enzyme cleaves the conjugate thereby releasing the drug. Depending upon the structure of the conjugate, a particular class or type of intracellular enzyme affects the cleavage. Due to the high demand for cobalamin in growing cells, tumor cells typically take up a higher percentage of the conjugate than do normal non-growing cells. The conjugate of the invention advantageously provides a reduced systemic toxicity and enhanced efficacy as compared to a corresponding free drug.

  本发明提供了一种适用于治疗肿瘤相关疾病的钴胺素-药物结合物。钴胺素通过可切割的连接剂间接共价结合到抗肿瘤药物上，还可以通过一个或多个可选的间隔物。钴胺素通过其核糖环的5'-OH与第一间隔物或可切割连接剂共价结合。药物通过其现有或添加的功能基团与可切割连接剂的第二间隔物结合。在给药后，结合物与转钴胺素（其任何同工异构体）形成复合物。然后，该复合物结合到细胞膜上的受体并被细胞摄取。一旦进入细胞，细胞内酶将切割结合物，从而释放药物。根据结合物的结构，特定类别或类型的细胞内酶影响切割。由于生长细胞对钴胺素的需求量较高，肿瘤细胞通常摄取结合物的比例高于正常非生长细胞。本发明的结合物与相应的游离药物相比，具有较低的全身毒性和增强的疗效。
• ANTI-B7-H3 ANTIBODIES AND ANTIBODY DRUG CONJUGATES
  申请人：AbbVie Inc.

  公开号：US20170355769A1

  公开（公告）日：2017-12-14

  The invention relates to B7 homology 3 protein (B7-H3) antibodies and antibody drug conjugates (ADCs), including compositions and methods of using said antibodies and ADCs.

  这项发明涉及B7同源物3蛋白（B7-H3）抗体和抗体药物结合物（ADCs），包括使用所述抗体和ADCs的组合物和方法。
• [EN] SUBSTITUTED 2-BENZYLIDENE-2H-BENZO[b][1,4]THIAZIN-3(4H)-ONES, DERIVATIVES THEREOF, AND THERAPEUTIC USES THEREOF<br/>[FR] 2-BENZYLIDÈNE-2H-BENZO[B][1,4]THIAZIN-3(4H)-ONES SUBSTITUÉES, DÉRIVÉS DE CELLES-CI, ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：UNIV TEMPLE

  公开号：WO2012166586A1

  公开（公告）日：2012-12-06

  The present invention relates to compounds according to Formula I and salts thereof, wherein R1, R2, R3, R4, Ar, and n are as defined herein. Methods for preparing compounds of Formula I are also provided. The present invention further includes methods of treating cellular proliferative disorders, such as cancer, with the compounds of Formula I.

  本发明涉及根据公式I的化合物及其盐，其中R1、R2、R3、R4、Ar和n如本文所述定义。还提供了制备公式I化合物的方法。本发明进一步包括使用公式I的化合物治疗细胞增殖障碍的方法，例如癌症。
• [EN] HYDROPHILIC LINKERS AND THEIR USES FOR CONJUGATION OF DRUGS TO CELL BINDING MOLECULES<br/>[FR] LIEURS HYDROPHILES ET LEURS UTILISATIONS POUR LA CONJUGAISON DE MÉDICAMENTS À DES MOLÉCULES SE LIANT AUX CELLULES
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2014080251A1

  公开（公告）日：2014-05-30

  Cell binding agent-drug conjugates comprising hydrophilic linkers, and methods of using such linkers and conjugates are provided.

  细胞结合剂-药物偶联物包括亲水性连接剂，并提供使用这种连接剂和偶联物的方法。
• Synthesis, characterization, and targeted chemotherapy of SCT200-linker-monomethyl auristatin E conjugates
  作者：Xinyue Hu、Hailun Jiang、Weiqi Bai、Xiujun Liu、Qingfang Miao、Linlin Wang、Jie Jin、Along Cui、Rui Liu、Zhuorong Li

  DOI：10.1016/j.ejmech.2021.113297

  日期：2021.4

  Antibody-drug conjugates (ADCs) are currently among the most successful and important strategies for treating patients with solid tumors. ADCs are composed of a monoclonal antibody and warhead, which are conjugated via a linker. Currently, monomethyl auristatin E (MMAE) is the most widely applied warhead in the development of ADCs. However, MMAE-based ADCs are generally constructed using the MC-VC-PABC

  抗体-药物偶联物（ADC）目前是治疗实体瘤患者最成功，最重要的策略之一。ADC由单克隆抗体和战斗部组成，它们通过连接子偶联。当前，单甲基耳他汀E（MMAE）是ADC开发中应用最广泛的战斗部。但是，基于MMAE的ADC通常使用MC-VC-PABC链接器构建，并且该设计具有有限的结构多样性和一些缺点。因此，在这项研究中，我们在ADC中生成了三种类型的新型接头-MMAE（与MC-VC-PABC-MMAE相比，间隔区，分解代谢区域和自消灭性改变），称为SCT200-接头-MMAE共轭物，然后评估连接蛋白的血浆稳定性和组织蛋白酶B的药物释放速率。结合能力，内在化速率，系统地研究了所有SCT200-linker-MMAE ADC的合成和功效，并评估了凋亡相关蛋白的表达以及SCT200-M-2，-C-2和-C-4的治疗效果。结果表明，对于表皮生长因子受体阳性的肿瘤，其中一些ADC的活性增加。此外，本研究