(R)-6-(4-氟苯基)-N,N-二甲基-3-[3-(3-吡啶基)-1H,3H-吡咯并[1,2-C]噻唑-7-YL]羰基-1H-吲哚-1-甲酰胺 | 161395-33-1

• 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
• 中文名称: (R)-6-(4-氟苯基)-N,N-二甲基-3-[3-(3-吡啶基)-1H,3H-吡咯并[1,2-C]噻唑-7-YL]羰基-1H-吲哚-1-甲酰胺
• 英文名称: (R)-7-<1-(N,N-dimethylcarbamoyl)-6-(4-fluorophenyl)indol-3-oyl>-1H,3H-pyrrolo<1,2-c>thiazole
• 英文别名: A 85783；6-(4-fluorophenyl)-N,N-dimethyl-3-[(3R)-3-pyridin-3-yl-1,3-dihydropyrrolo[1,2-c][1,3]thiazole-7-carbonyl]indole-1-carboxamide
• CAS: 161395-33-1
• 化学式: C₂₉H₂₃FN₄O₂S
• 分子量: 510.592
• InChiKey: YGUVFPOGHIKVPP-MUUNZHRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  85.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-(4-氟苯基)吲哚 在 氢氧化钾 、 乙基溴化镁 、 zinc(II) chloride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 (R)-6-(4-氟苯基)-N,N-二甲基-3-[3-(3-吡啶基)-1H,3H-吡咯并[1,2-C]噻唑-7-YL]羰基-1H-吲哚-1-甲酰胺
  参考文献：
  名称：

  N-(Acyloxyalkyl)pyridinium Salts as Soluble Prodrugs of a Potent Platelet Activating Factor Antagonist

  摘要：

  Pyrrolothiazole 4 is a potent antagonist of platelet activating factor-mediated effects in a variety of in vitro and in vivo assays. Despite its positive activity in models of inflammation and septic shock, 4 lacks the aqueous solubility necessary for intravenous administration. This deficit was overcome by conversion of 4 to water-soluble pyridinium prodrugs. A two-step procedure was used to prepare a series of N-(acyloxyalkyl)pyridinium salts, all of which exhibited aqueous solubility of greater than 20 mg/mL. The rate of conversion of these prodrugs to 4 was faster in human plasma than in pH 7 aqueous buffer. This rate difference was shown to be due to serum enzymes since the conversion in plasma was significantly slower in the presence of a serine esterase inhibitor. A strong correlation between prodrug structure and buffer/plasma half-life was established. The N-(acetyloxymethyl)pyridinium prodrug 11 (ABT-299) is currently undergoing clinical evaluation for the treatment of sepsis.

  DOI：

  10.1021/jm00052a001

文献信息

• N-(Acyloxyalkyl)pyridinium Salts as Soluble Prodrugs of a Potent Platelet Activating Factor Antagonist
  作者：Steven K. Davidsen、James B. Summers、Daniel H. Albert、James H. Holms、H. Robin Heyman、Terrance J. Magoc、Richard G. Conway、David A. Rhein、George W. Carter

  DOI：10.1021/jm00052a001

  日期：1994.12

  Pyrrolothiazole 4 is a potent antagonist of platelet activating factor-mediated effects in a variety of in vitro and in vivo assays. Despite its positive activity in models of inflammation and septic shock, 4 lacks the aqueous solubility necessary for intravenous administration. This deficit was overcome by conversion of 4 to water-soluble pyridinium prodrugs. A two-step procedure was used to prepare a series of N-(acyloxyalkyl)pyridinium salts, all of which exhibited aqueous solubility of greater than 20 mg/mL. The rate of conversion of these prodrugs to 4 was faster in human plasma than in pH 7 aqueous buffer. This rate difference was shown to be due to serum enzymes since the conversion in plasma was significantly slower in the presence of a serine esterase inhibitor. A strong correlation between prodrug structure and buffer/plasma half-life was established. The N-(acetyloxymethyl)pyridinium prodrug 11 (ABT-299) is currently undergoing clinical evaluation for the treatment of sepsis.