Cam-4580 | 174885-89-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Cam-4580
• 英文别名: L-Leucine (2R)-2-[[(2R)-2-[[(2-benzofuranylmethoxy)carbonyl]amino]-3-(1H-indol-3-yl)-2-methyl-1-oxopropyl]amino]-2-phenylethyl ester；[(2R)-2-[[(2R)-2-(1-benzofuran-2-ylmethoxycarbonylamino)-3-(1H-indol-3-yl)-2-methylpropanoyl]amino]-2-phenylethyl] (2S)-2-amino-4-methylpentanoate
• CAS: 174885-89-3
• 化学式: C₃₆H₄₀N₄O₆
• 分子量: 624.737
• InChiKey: QSDHIFQFLSUMRP-DDCZIVEXSA-N

反应信息

• 作为产物：
  描述：

  Cam-4451 在 4-二甲氨基吡啶 甲酸 、 水 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 苯甲醚 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 Cam-4580
  参考文献：
  名称：

  摘要：

  Purpose. The purpose of this research was to examine a targeted prodrug strategy to increase the absorption of a poorly water-soluble lipophilic compound.Methods. Three water-soluble prodrugs of Cam-4451 were synthesized. The amino acid (Cam-4562, Cam-4580) or phosphate (Cam-5223) ester prodrugs introduced moieties ionized at physiological pn and targeted intestinal brush-border membrane enzymes fur reconversion to the parent. Selectivity for reconversion of the three prodrugs was examined in rat intestinal perfusate and brush-border membrane suspensions. Bioavailability of Cam-4451 in rats was evaluated after administering orally as the parent or as prodrugs in a cosolvent vehicle or in methylcellulose.Results. Cam-5223 was highly selective for reconversion at the brush-border, but was rapidly reconverted in intestinal perfusate. Cam-4562 was not as selective but was more stable in the perfusate, whereas Cam-4580 was neither selective nor stable. Oral bioavailability of Cam-4451 was 14% after dosing as the parent in the cosolvent vehicle, 39% and 46%, respectively, as Cam-4562 and Cam-5223. Oral bioavailability was only 3.6% when the parent was dosed in methylcellulose, whereas the bioavailability was 7-fold higher when dosed as the phosphate predrug.Conclusions. Water-soluble prodrugs that target brush-border membrane enzymes for reconversion can be useful in improving drug oral bioavailability.

  DOI：

  10.1023/a:1011969808907