2-(3a,5,8b-Tribromo-7-methylsulfonyl-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid | 625820-67-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-(3a,5,8b-Tribromo-7-methylsulfonyl-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid
• CAS: 625820-67-9
• 化学式: C₁₄H₁₄Br₃NO₄S
• 分子量: 532.047
• InChiKey: PRMCYHZITMAZAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  91.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(3a,5,8b-Tribromo-7-methylsulfonyl-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid 在 tris(dibenzylideneacetone)dipalladium (0) sodium hydroxide 、 三苯胂 、 sodium hydride 、 溶剂黄146 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 [5-acetyl-4-(4-chlorobenzyl)-7-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]acetic acid
  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：

  2-氧代环戊基乙酸乙酯 在 吡啶 、 palladium diacetate 、 sodium hydroxide 、 硅酸四乙酯 、 4-甲基苯磺酸吡啶 、 pyridinium hydrobromide perbromide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 2-(3a,5,8b-Tribromo-7-methylsulfonyl-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid
  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

• Efficient synthesis of bromocyclopenta[<i>b</i>] indoles via a bromination - reduction sequence
  作者：Nicolas Lachance、Wing Yan Chan

  DOI：10.1002/jhet.5570400214

  日期：2003.3

  Substituted cyclopenta[b]indoles are selectively brominated in good yields with excess pyridine - Br2 charge-transfer complex (PyBr2) in a one-pot reaction to provide 5 and/or 7-bromoindoles. The mechanism involves the formation of an adduct (addition of bromine on the central double bond) which is subsequently reduced in situ with Zn and AcOH. A variety of functional groups in the cyclopentyl and

  在一锅反应中，用过量的吡啶-Br 2电荷转移络合物（PyBr 2）以高收率选择性地取代取代的环戊[ b ]吲哚，以提供5和/或7-溴吲哚。该机理涉及形成加合物（在中心双键上加成溴），其随后被Zn和AcOH原位还原。环戊基和苯环中的各种官能团是可容忍的。