methyl 2-(5-bromo-7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate | 571170-85-9

• 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: methyl 2-(5-bromo-7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate
• CAS: 571170-85-9
• 化学式: C₁₄H₁₃BrFNO₂
• 分子量: 326.165
• InChiKey: WMRIQGACMWNBKN-UHFFFAOYSA-N

物化性质

• 沸点：
  426.8±40.0 °C(Predicted)
• 密度：
  1.561±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.66
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  42.09
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  methyl 2-(5-bromo-7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate 在 sodium hydroxide 、 copper(l) iodide 、 (S)-(-)-1-(1-naphthyl)ethylamine salt 、 sodium hydride 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 拉罗皮兰
  参考文献：
  名称：

  Discovery of a Potent and Selective Prostaglandin D₂ Receptor Antagonist, [(3R)-4-(4-Chloro- benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic Acid (MK-0524)

  摘要：

  The discovery of the potent and selective prostaglandin D-2 (PGD(2)) receptor (DP) antagonist [(3R)-4-(4-chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (13)is presented. Initial lead antagonists 6and 7were found to be potent and selective DP antagonists (DP K-i = 2.0 nM for each); however, they both suffered from poor pharmacokinetic profiles, short half-lives and high clearance rates in rats. Rat bile duct cannulation studies revealed that high concentrations of parent drug were present in the biliary fluid (C-max = 1100 mu M for 6and 3900 mu M for 7). This pharmacokinetic liability was circumvented by replacing the 7-methylsulfone substituent present in 6and 7with a fluorine atom resulting in antagonists with diminished propensity for biliary excretion and with superior pharmacokinetic profiles. Further optimization led to the discovery of the potent and selective DP antagonist 13.

  DOI：

  10.1021/jm0603668
• 作为产物：
  描述：

  7-氟-5-溴-1,2,3,4-四氢乙酯 在 吡啶 、 盐酸 、 sodium hydroxide 、 溶剂黄146 、 pyridinium hydrobromide perbromide 、 锌 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 methyl 2-(5-bromo-7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate
  参考文献：
  名称：

  Discovery of a Potent and Selective Prostaglandin D₂ Receptor Antagonist, [(3R)-4-(4-Chloro- benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic Acid (MK-0524)

  摘要：

  The discovery of the potent and selective prostaglandin D-2 (PGD(2)) receptor (DP) antagonist [(3R)-4-(4-chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (13)is presented. Initial lead antagonists 6and 7were found to be potent and selective DP antagonists (DP K-i = 2.0 nM for each); however, they both suffered from poor pharmacokinetic profiles, short half-lives and high clearance rates in rats. Rat bile duct cannulation studies revealed that high concentrations of parent drug were present in the biliary fluid (C-max = 1100 mu M for 6and 3900 mu M for 7). This pharmacokinetic liability was circumvented by replacing the 7-methylsulfone substituent present in 6and 7with a fluorine atom resulting in antagonists with diminished propensity for biliary excretion and with superior pharmacokinetic profiles. Further optimization led to the discovery of the potent and selective DP antagonist 13.

  DOI：

  10.1021/jm0603668

文献信息

• Fluoro substituted cycloalkanoindoles, compositions containing such compounds and methods of treatment
  申请人：Merck Frosst Canada & Co.

  公开号：US07317036B2

  公开（公告）日：2008-01-08

  Fluoro substituted cycloalkanoindole derivatives are antagonists of prostaglandins, and as such are useful for the treatment of prostaglandin mediated diseases.

  氟代环烷基吲哚衍生物是前列腺素拮抗剂，因此对于治疗前列腺素介导的疾病是有用的。
• [EN] NIACIN RECEPTOR AGONISTS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT<br/>[FR] AGONISTES DES RECEPTEURS DE NIACINE, COMPOSITIONS CONTENANT LESDITS COMPOSES ET METHODES DE TRAITEMENT
  申请人：MERCK & CO INC

  公开号：WO2006052555A3

  公开（公告）日：2006-06-22
• [EN] METHOD OF TREATING ATHEROSCLEROSIS, DYSLIPIDEMIAS AND RELATED CONDITIONS<br/>[FR] PROCEDE POUR TRAITER L'ATHEROSCLEROSE, LA DYSLIPIDEMIE ET LES ETATS PATHOLOGIQUES ASSOCIES
  申请人：MERCK & CO INC

  公开号：WO2006026273A3

  公开（公告）日：2006-09-08
• WO2006/89309
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• WO2006/113150
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