N⁴-n-butyryl gemcitabine | 1374587-08-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N⁴-n-butyryl gemcitabine
• 英文别名: N-[1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]butanamide
• CAS: 1374587-08-2
• 化学式: C₁₃H₁₇F₂N₃O₅
• 分子量: 333.292
• InChiKey: UEOCXVZQUVACSZ-AVPPRXQKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  吉西他滨 、 1-丁酰咪唑 在 吡啶 、 三乙基氯硅烷 、 三氟乙酸 作用下， 以 乙腈 、 甲醇 为溶剂， 反应 2.0h， 生成 N⁴-n-butyryl gemcitabine
  参考文献：
  名称：

  GEMCITABINE AMIDE DERIVATIVE AND PREPARATION METHOD AND USE THEREOF

  摘要：

  本发明涉及医疗技术领域，具体涉及一种具有新颖结构的吉西他滨酰胺衍生物。本发明的新化合物对人类肺癌、结肠癌、乳腺癌和肝癌等多种肿瘤细胞具有很高的活性，因此可用于制备抗肿瘤药物。此外，这些化合物还具有抗病毒活性。还公开了这些化合物的制备方法、含有这些化合物的药物组合物以及它们在制备抗肿瘤和抗病毒药物等方面的用途。

  公开号：

  US20140235568A1

文献信息

• Combination of <scp>l</scp>-Carnitine with Lipophilic Linkage-Donating Gemcitabine Derivatives as Intestinal Novel Organic Cation Transporter 2-Targeting Oral Prodrugs
  作者：Gang Wang、Hongxiang Chen、Dongyang Zhao、Dawei Ding、Mengchi Sun、Longfa Kou、Cong Luo、Dong Zhang、Xiulin Yi、Jinhua Dong、Jian Wang、Xiaohong Liu、Zhonggui He、Jin Sun

  DOI：10.1021/acs.jmedchem.7b00049

  日期：2017.3.23

  Novel organic cation transporter 2 (OCTN2, SLC22A5) is responsible for the uptake of carnitine through the intestine and, therefore, might be a promising molecular target for designing oral prodrugs. Poor permeability and rapid metabolism have greatly restricted the oral absorption of gemcitabine. We here describe the design of intestinal OCTN2-targeting prodrugs of gemcitabine by covalent coupling of L-carnitine to its N4-amino group via different lipophilic linkages. Because of the high OCTN2 affinity, the hexane diacid-linked prodrug demonstrated significantly improved stability (3-fold), cellular permeability (15-fold), and oral bioavailability (5-fold), while causing no toxicity as compared to gemcitabine. In addition, OCTN2-targeting prodrugs can simultaneously improve the permeability, solubility, and metabolic stability of gemcitabine. In summary, we present the first evidence that OCTN2 can act as a new molecular target for oral prodrug delivery and, importantly, the linkage carbon chain length is a key factor in modifying the affinity of the substrate for OCTN2.
• EP3752511A1
  申请人：——

  公开号：EP3752511A1

  公开（公告）日：2020-12-23
• PHOSPHOR(N)AMIDATACETAL AND PHOSPH(ON)ATALCETAL COMPOUNDS
  申请人：NUCORION PHARMACEUTICALS, INC.

  公开号：US20210188887A1

  公开（公告）日：2021-06-24

  Provided herein are phosphor(n)amidatacetal and phosph(on)atacetal compounds, their preparation and their uses, such as treating liver diseases or nonliver diseases via intervening in the molecular pathways in the liver.