1-丙酮,1-[(1R,2S,3S,5S)-8-甲基-3-[4-(1-甲基乙基)苯基]-8-氮杂二环[3.2.1]辛-2-基]- | 162809-72-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 中文名称: 1-丙酮,1-[(1R,2S,3S,5S)-8-甲基-3-[4-(1-甲基乙基)苯基]-8-氮杂二环[3.2.1]辛-2-基]-
• 英文名称: 8-methyl-2β-propanoyl-3β-(p-isopropylphenyl)-8-azabicyclo<3.2.1>octane
• 英文别名: WF-31；1-[(1R,2S,3S,5S)-8-methyl-3-(4-propan-2-ylphenyl)-8-azabicyclo[3.2.1]octan-2-yl]propan-1-one
• CAS: 162809-72-5
• 化学式: C₂₀H₂₉NO
• 分子量: 299.456
• InChiKey: BVSOMKYAWFJCTH-XFKSJGNHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  富马酸 、 1-丙酮,1-[(1R,2S,3S,5S)-8-甲基-3-[4-(1-甲基乙基)苯基]-8-氮杂二环[3.2.1]辛-2-基]- 以 异丙醇 为溶剂， 以94%的产率得到8-methyl-2β-propanoyl-3β-(4-(1-methylethyl)phenyl)-8-azabicyclo[3.2.1]octane fumarate
  参考文献：
  名称：

  Hemby; Lucki; Gatto, Journal of Pharmacology and Experimental Therapeutics, 1997, vol. 282, # 2, p. 727 - 733

  摘要：

  DOI：
• 作为产物：
  描述：

  5-己烯-3-酮 在 RhCl(PPh₃)3 rhodium(II) octanoate 、 copper bromide-dimethyl sulfide 、 4-乙酰氨基苯磺酰叠氮 、 氢气 、 sodium cyanoborohydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三氟乙酸 作用下， 以 乙醚 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 乙腈 为溶剂， 25.0 ℃ 、310.27 kPa 条件下， 反应 18.25h， 生成 1-丙酮,1-[(1R,2S,3S,5S)-8-甲基-3-[4-(1-甲基乙基)苯基]-8-氮杂二环[3.2.1]辛-2-基]-
  参考文献：
  名称：

  Synthesis of 2.beta.-Acyl-3.beta.-aryl-8-azabicyclo[3.2.1]octanes and Their Binding Affinities at Dopamine and Serotonin Transport Sites in Rat Striatum and Frontal Cortex

  摘要：

  A novel entry to tropane analogs of cocaine was developed on the basis of the reaction of rhodium-stabilized vinylcarbenoids with pyrroles. These analogs were tested:in binding to dopamine and serotonin (5-HT) transporters in:membranes from rat striatum and frontal cortex. In all the analogs, the aryl group at the 3-position was directly bound to the tropane ring (as in WIN-35,428), and methyl or ethyl ketone moieties were present at the a-position instead of the typical ester group. The series of analogs containing a 2-naphthyl group at the 3-position were most potent, with K-i values < 1 nM in binding to both dopamine and 5-HT transporters. Although the unsubstituted 2-naphthyl analog was nonselective at dopamine and 5-HT transport sites, other compounds:were selective for either site. In general, compounds with relatively small substituents on the aromatic moiety (such as p-methyl or p-fluoro) were relatively selective for the dopamine transporters, while a p-isopropylphenyl derivative was selective:for the 5-HT transport sites. This latter compound represents the first N-methyltropane derivative specific for 5-HT transporters. Resolution of two of the most significant analogs was achieved by HPLC on a chiral stationary phase; the active enantiomer of a 2-naphthyl analog exhibited K-i values of <0.1 nM at both dopamine and 5-HT transporter sites.

  DOI：

  10.1021/jm00035a005