RN 1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: RN 1
• 英文别名: Retinoyloxymethyl Butyrate；butanoyloxymethyl (2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoate
• 化学式: C₂₅H₃₆O₄
• 分子量: 400.558
• InChiKey: CVKNZADKHLEGHJ-GHSBTYJGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  丁酸氯甲酯 、 维A酸 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以68%的产率得到RN 1
  参考文献：
  名称：

  Novel Mutual Prodrug of Retinoic and Butyric Acids with Enhanced Anticancer Activity

  摘要：

  Acyloxylalkyl esters of retinoic acid and small carboxylic acids (C3-5) were evaluated for anticancer activity. The derivative of butyric acid (BA) and alh-trans-retinoic acid (ATRA) retinoyloxymethyl butyrate (RN1) - acting as a mutual prodrug was a more potent inducer of cancer cell differentiation and inhibitor of proliferation than the parent acids. ED50 Of RN1 for differentiation induction in HL-60 was over 40-fold lower than that of ATRA. The differentiating activity of ATRA compared to that of the acyloxylalkyl esters derived from butyric (RN1), propionic (RN2), isobutyric (RN3), and pivalic (RN4) acids was found to be: RN1 > RN2 > RN3 > ATRA similar to RN4. This observation implies that the activity of the prodrugs depends on the specific acyl fragment attached to the retinoyl moiety, and the butyroyl fragment conferred the highest potency. The IC50 values for inhibition of Lewis lung (3LLD122) and pancreatic (PaCa2) carcinoma cell line colony formation elicited by RN1 were significantly higher than those of ATRA. In addition to its superiority over ATRA or BA as growth inhibitors of the above cell Lines, RN1 was also able to overcome the resistance to ATRA in 3LLD122 cells.

  DOI：

  10.1021/jm990540a

文献信息

• Retinoyloxy (substituted) methyl butyrates useful for the treatment of
  申请人：Bar-Ilan University

  公开号：US05710176A1

  公开（公告）日：1998-01-20

  This invention relates to the novel compounds of Formula (I) and pharmaceutical compositions containing same, to methods of treating, preventing or ameliorating cancer and other proliferative diseases in a subject in need of such treatment comprising administering a compound of Formula (I) and pharmaceutically acceptable salts and prodrugs thereof. ##STR1##

  这项发明涉及到公式(I)的新化合物以及含有这些化合物的药物组合物，以及治疗、预防或改善患有癌症和其他增殖性疾病的受试者的方法，包括给予公式(I)的化合物及其药用盐和前药。
• MUTUAL PRODRUGS AND METHODS TO TREAT CANCER
  申请人：Njar Vincent C. O.

  公开号：US20100184812A1

  公开（公告）日：2010-07-22

  Mutual prodrugs comprising retinoids and histone deacetylase inhibitors, methods for production of the mutual prodrugs, and methods of treatment comprising administration of the mutual prodrugs. The retinoids include all-trans retinoic acid, 13-cis retinoic acid, and retinoic acid analogs that have a substitution at C-4. Further, the mutual prodrugs of the present invention can be used as therapeutic agents for the treatment of cancer and dermatological diseases and conditions. Pharmaceutical compositions comprising the mutual prodrugs.

  相互药物包括视黄醇和组蛋白去乙酰化酶抑制剂，制备相互药物的方法以及包括给予相互药物的治疗方法。视黄醇包括全反式视黄酸、13-顺式视黄酸和在C-4处有取代基的视黄酸类似物。此外，本发明的相互药物可用作治疗癌症和皮肤病的治疗剂。药物组成物包括相互药物。
• ガンおよび他の細胞増殖性疾患の治療に有用なレチノイルオキシ（置換）アルキレンブチレート
  申请人：——

  公开号：JP2002514161A

  公开（公告）日：2002-05-14

  \n (57)【要約】\n本発明は、新規なレチノイルオキシ（置換）アルキレンブチレート化合物、および、これを含んでいる医薬組成物、並びに、本治療を必要とする対象者において、ガンおよび他の細胞増殖性疾患を治療、予防または軽減する方法であって、前記化合物、これの医薬的に容認されている塩またはプロドラッグを対象者に投与することを含んでいる前記方法に関する。本発明の化合物はまた、ヒストンデアセチラーゼの阻害、しわの軽減、皮膚科学上の疾患の治療または軽減、傷の治癒の促進、皮膚の潰瘍の治療、および胃腸疾患の治療のための方法においても有用である。\n

  \本发明涉及新型视黄酰氧基(取代)亚烷基丁酸酯化合物和含有该化合物的药物组合物，以及治疗、预防或减轻需要本发明治疗的受试者的癌症和其他细胞增殖性疾病的方法，所述化合物、其药学上可接受的盐或原药。治疗、预防或减轻需要本疗法的受试者的癌症和其他细胞增殖性疾病的方法，包括向受试者施用所述化合物、其药学上可接受的盐或原药。本发明的化合物还可用于抑制组蛋白去乙酰化酶、减少皱纹、治疗或减轻皮肤病、促进伤口愈合、治疗皮肤溃疡和治疗胃肠道疾病。\n
• US6040342
  申请人：——

  公开号：——

  公开（公告）日：——
• RETINOYLOXY(SUBSTITUTED)ALKYLENE BUTYRATES USEFUL FOR THE TREATMENT OF CANCER AND OTHER PROLIFERATIVE DISEASES
  申请人：BAR-ILAN UNIVERSITY

  公开号：EP0927033A1

  公开（公告）日：1999-07-07