p-Maleinimidophenylacetic acid chloride | 188985-00-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: p-Maleinimidophenylacetic acid chloride
• 英文别名: 2-[4-(2,5-dioxopyrrol-1-yl)phenyl]acetyl chloride
• CAS: 188985-00-4
• 化学式: C₁₂H₈ClNO₃
• 分子量: 249.653
• InChiKey: FTAZNACPXCKILQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  54.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  p-Maleinimidophenylacetic acid chloride 以 四氢呋喃 为溶剂， 反应 3.33h， 生成
  参考文献：
  名称：

  Synthese von neuen bifunktionellen Maleinimidverbindungen zur Herstellung von Chemoimmunokonjugaten

  摘要：

  Bifunctional maleimide compounds are suitable for binding small molecules to carrier proteins in that they bind to the sulfhydryl group of proteins through the double bond of the maleimide group and to molecules of low molecular weight (e.g. anticancer drugs) through a functional group X. 18 maleimide compounds of the general formula Maleimid-R-X (R = phenylene, benzyl-, methylene-, ethylene, or a m-benzoylethylamide group and X = hydroxp-, amino-, hydrazino-, carboxylic acid-, carboxylic anhydride-, carboxylic acid chloride-, carboxylic acid hydrazide-, oxycarbonylchloride-, aldehyde, keto-, or p-toluenesulfonate-group) were synthesized and characterized through H-1- and C-13-NMR-spectroscopy, elemental analysis, and mass spectrometry.

  DOI：

  10.1007/bf00807643
• 作为产物：
  描述：

  2-(4-马来酰亚胺基苯基)乙酸 在 草酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以59%的产率得到p-Maleinimidophenylacetic acid chloride
  参考文献：
  名称：

  Synthese von neuen bifunktionellen Maleinimidverbindungen zur Herstellung von Chemoimmunokonjugaten

  摘要：

  Bifunctional maleimide compounds are suitable for binding small molecules to carrier proteins in that they bind to the sulfhydryl group of proteins through the double bond of the maleimide group and to molecules of low molecular weight (e.g. anticancer drugs) through a functional group X. 18 maleimide compounds of the general formula Maleimid-R-X (R = phenylene, benzyl-, methylene-, ethylene, or a m-benzoylethylamide group and X = hydroxp-, amino-, hydrazino-, carboxylic acid-, carboxylic anhydride-, carboxylic acid chloride-, carboxylic acid hydrazide-, oxycarbonylchloride-, aldehyde, keto-, or p-toluenesulfonate-group) were synthesized and characterized through H-1- and C-13-NMR-spectroscopy, elemental analysis, and mass spectrometry.

  DOI：

  10.1007/bf00807643

文献信息

• Synthesis and Stability of Four Maleimide Derivatives of the Anticancer Drug Doxorubicin for the Preparation of Chemoimmunoconjugates.
  作者：Michael KRUGER、Ulrich BEYER、Peter SCHUMACHER、Clemens UNGER、Heike ZAHN、Felix KARTZ

  DOI：10.1248/cpb.45.399

  日期：——

  By attaching maleimide groups to anticancer drugs, derivatives are obtained which bind selectively to thiolated carrier proteins. Four maleimide derivatives of the anticancer drug doxorubicin were prepared in which 3-maleimidobenzoic acid or 4-maleimidophenylacetic acid was bound to the 3'-amino position of doxorubicin through a benzoyl or phenylacetyl amide bond (1 or 2) or in which 3-maleimidobenzoic acid hydrazide or 4-maleimidophenylacetic acid hydrazide was bound to the 13-keto position through a benzoyl or phenylacetyl hydrazone bond (3 or 4). The maleimide derivatives of doxorubicin were characterized by means of 13C-NMR spectroscopy, elemental analysis and mass spectrometry. In addition, the stability of the maleimide derivatives 1-4 at pH values of 5.0 and 7.4 was investigated with the aid of HPLC. The amide or hydrazone bond of 1-4 is stable at pH 7.4 whereas the hydrazone bond is acid-sensitive.

  通过将马来酰亚胺基团连接到抗癌药物上，可以获得选择性地与硫醇载体蛋白结合的衍生物。我们制备了抗癌药物多柔比星的四种马来酰亚胺衍生物，其中 3-马来酰亚胺苯甲酸或 4-马来酰亚胺苯乙酸通过苯甲酰基或苯乙酰基酰胺键（1 或 2）与多柔比星的 3'-氨基位置结合，或者 3-马来酰亚胺苯甲酸酰肼或 4-马来酰亚胺苯乙酸通过苯甲酰基或苯乙酰基酰胺键（1 或 2）与多柔比星的 3'-氨基位置结合。马来酰亚胺苯甲酸酰肼或 4-马来酰亚胺苯乙酸酰肼通过苯甲酰基或苯乙酰基腙键与 13-酮位结合（3 或 4）。多柔比星的马来酰亚胺衍生物通过 13C-NMR 光谱、元素分析和质谱法进行了表征。此外，还借助高效液相色谱法研究了马来酰亚胺衍生物 1-4 在 pH 值为 5.0 和 7.4 时的稳定性。1-4 的酰胺键或腙键在 pH 值为 7.4 时是稳定的，而腙键对酸敏感。
• Antineoplastic conjugates of transferrin, albumin and polyethylene glycol
  申请人：——

  公开号：US20020019343A1

  公开（公告）日：2002-02-14

  Conjugates of transferrin, albumin and polyethylence glycol consisting of native or thiolated transferrin or albumin or of polyethylene glycol (MW between approximately 5,000 and 20,0000) with at least one HS—, HO— or H 2 N group and cytostatic compounds derived through maleinimide or N-hydroxysuccinimide ester compounds, such as doxorubicin, daunorubicin, epirubicin, idarubicin, mitoxandrone, chloroambucil, melphalan, 5-fluorouracyl, 5′-desoxy-5-fluorouridine, thioguanine, methotrexate, paclitaxel, docetaxel, topotecan, 9-aminocamptothecin, etoposide, teniposide, mitopodoside, vinblastine, vincristine, vindesine, vinorelbine or a compound of general formula A, B, C or D, where n=0-6, X=—NH 2 , —OH, —COOH, —O—CO—R—COR*, —NH—CO—R—COR*, where R is an aliphatic carbon chain with 1-6 carbon atoms or a substituted or unsubstituted phenylene group and R* H, phenyl, alkyl with 1-6 carbon atoms.

  转铁蛋白、白蛋白和聚乙二醇的共轭物，包括具有至少一个HS—、HO—或H2N基团的天然或硫醇化的转铁蛋白或白蛋白或聚乙二醇（分子量约在5,000至20,000之间），以及通过马来酰亚胺或N-羟基琥珀酰亚胺酯类化合物衍生的细胞毒素化合物，如多柔比星、多诺西星、依吡螺星、伊达鲁比汀、米托蒽醌、氯乙酰胺、甲氨蝶呤、5-氟尿嘧啶、5'-脱氧-5-氟尿嘧啶、硫鸟嘌呤、甲氨蝶呤、紫杉醇、多西他赛、托泊替尼、9-氨基喜树碱、依托泊苷、替尼泊苷、米托泼苷、长春新碱、长春烷醇、长春烯胺、长春诺宾或A、B、C或D通式的化合物，其中n=0-6，X=-NH2、-OH、-COOH、-O-CO-R-COR*、-NH-CO-R-COR*，其中R是具有1-6个碳原子的脂肪族碳链或取代或未取代的苯基基团，R*是氢、苯基或具有1-6个碳原子的烷基。
• Antineoplastic conjugates of transferin, albumin and polyethylene glycol
  申请人：——

  公开号：US06709679B2

  公开（公告）日：2004-03-23

  Conjugates of transferrin, albumin and polyethylence glycol consisting of native or thiolated transferrin or albumin or of polyethylene glycol (MW between approximately 5,000 and 20,0000) with at least one HS—, HO— or H2N group and cytostatic compounds derived through maleinimide or N-hydroxysuccinimide ester compounds, such as doxorubicin, daunorubicin, epirubicin, idarubicin, mitoxandrone, chloroambucil, melphalan, 5-fluorouracyl, 5′-desoxy-5-fluorouridine, thioguanine, methotrexate, paclitaxel, docetaxel, topotecan, 9-aminocamptothecin, etoposide, teniposide, mitopodoside, vinblastine, vincristine, vindesine, vinorelbine or a compound of general formula A, B, C or D, where n=0-6, X=—NH2, —OH, —COOH, —O—CO—R—COR*, —NH—CO—R—COR*, where R is an aliphatic carbon chain with 1-6 carbon atoms or a substituted or unsubstituted phenylene group and R*H, phenyl, alkyl with 1-6 carbon atoms.

  转铁蛋白、白蛋白和聚乙二醇的共轭物，包括具有至少一个HS—、HO—或H2N基团的天然或硫化的转铁蛋白或白蛋白或聚乙二醇（分子量约为5,000至20,0000之间），以及通过马来酰亚胺或N-羟基琥珀酰亚胺酯类化合物衍生的细胞毒性化合物，例如多柔比星、多诺西星、艾匹霉素、伊达霉素、米托蒽醌、氯乙酰胺、甲氨蝶呤、5-氟尿嘧啶、5'-脱氧-5-氟尿嘧啶、硫鸟嘌呤、甲氨蝶呤、紫杉醇、多西他赛、托泊替尼、9-氨基喜树碱、依托泊苷、替尼泊苷、米托波顿、长春新碱、长春烷碱、长春诺碱或一般式A、B、C或D的化合物，其中n＝0-6，X＝—NH2、—OH、—COOH、—O—CO—R—COR*、—NH—CO—R—COR*，其中R是具有1-6个碳原子的脂肪族碳链或取代或未取代的苯基基团，R*是氢、苯基或具有1-6个碳原子的烷基。
• Beyer; Schumacher; Unger, Pharmazie, 1997, vol. 52, # 6, p. 480 - 481
  作者：Beyer、Schumacher、Unger、Frahm、Kratz

  DOI：——

  日期：——
• US6310039B1
  申请人：——

  公开号：US6310039B1

  公开（公告）日：2001-10-30