3-Iodocytisine | 444808-61-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 羽扇豆生物碱
• 英文名称: 3-Iodocytisine
• 英文别名: 9-iodocytisine；(1R,9S)-5-iodo-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one
• CAS: 444808-61-1
• 化学式: C₁₁H₁₃IN₂O
• 分子量: 316.142
• InChiKey: GQVTUDRXPMPVRX-JGVFFNPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-3-(1-methyl-1H-imidazol-4-yl)-2-propenoic acid 、 3-Iodocytisine 在 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以86%的产率得到(1R,5S)-9-iodo-3-[(2E)-3-(1-methyl-1H-imidazol-4-yl)prop-2-enoyl]-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one
  参考文献：
  名称：

  9- 和 11-卤代胞嘧啶与 1'-N-甲基尿烷酸的结合物

  摘要：

  通过使用 N-羟基琥珀酰亚胺将 9- 和 11-卤代取代的胞嘧啶与 1'-N-甲基尿烷酸结合，合成了新的 (-)-胞嘧啶衍生物。

  DOI：

  10.1007/s10600-019-02905-2
• 作为产物：
  描述：

  cytisine 在 N-碘代丁二酰亚胺 、 三氟乙酸 作用下， 反应 5.0h， 以46%的产率得到3-Iodocytisine
  参考文献：
  名称：

  Iodination of Cytisine and Methylcytisine Alkaloids

  摘要：

  在酸性溶液中，(–)-金雀花碱和甲基金雀花碱的 2-吡啶酮核心被一当量的 ICl 或 N-碘代琥珀酰亚胺 (NIS) 碘化，主要得到 9-碘衍生物，尽管起始生物碱未完全转化。在相同条件下使用过量的试剂得到9,11-二碘代衍生物，产率分别为72%和76%。 9-碘甲基金雀花碱的制备方法如下：在三氟乙酸中用过量的 NIS 处理甲基金雀花碱，然后在乙醇和 HCl 水溶液的混合物中用锌粉对 9,11-二碘代衍生物进行脱碘。

  DOI：

  10.1007/s10600-019-02904-3

文献信息

• Syntheses and evaluation of halogenated cytisine derivatives and of bioisosteric thiocytisine as potent and selective nAChR ligands
  作者：P Imming

  DOI：10.1016/s0223-5234(01)01222-3

  日期：2001.4

  We have developed one-step syntheses of halogenated derivatives of (-)-cytisine featuring a halogen substituent at positions 3, 5 or 3 and 5 of the 2-pyridone fragment, and prepared the novel bioisosteric thiocytisine by oxygen-sulphur exchange. The affinities of these pyridone-modified analogs of (-)-cytisine for (alpha (4))(2)(beta (2)),(3) and alpha7* nAChRs in rat forebrain membranes were determined by competition with (+/-)-[H-3]epibatidine and [H-3]MLA, respectively. The 3-halocytisines 7 possess subnanomolar affinities for (alpha4)(2)(beta2)(3) nAChRs, higher than those found for (-)-cytisine as well as for the 5-halocytisines 8 and 3,5-dihalocytisines 6. In contrast to the parent alkaloid the 3-halogenated species display much a higher affinity for the alpha7* nAChR subtype. The most potent molecule was 3-bromocytisine (7b) with preferential selectivity (200-fold) for the (alpha4)(2)(beta2)(3) subtype [K-i = 10 pM (alpha4 beta2) and 2.0 nM (alpha7*)]. Replacement of the lactam with a thiolactam pharmacophore to thiocytisine (12) resulted in a subnanomolar affinity for the (alpha4)(2)(beta2)(3) nAChR subtype (K-i = 0.832 nM), but in a drastic decrease of affinity for the alpha7* subtype; thiocytisine (12) has a K-i value of 4000 nM (alpha7*), giving a selectivity of 4800-fold for the neuronal (alpha4)(2)(beta2)(3)-nAChR and thus displaying the best affinity-selectivity profile in the series under consideration. (C) 2001 Editions scientifiques et medicales Elsevier SAS.
• Iodination of Cytisine and Methylcytisine Alkaloids
  作者：A. V. Koval’skaya、P. R. Petrova、A. N. Lobov、I. P. Tsypysheva

  DOI：10.1007/s10600-019-02904-3

  日期：2019.11

  Iodination of the 2-pyridone core of (–)-cytisine and methylcytisine by one equivalent of ICl or N-iodosuccinimide (NIS) in acidic solution gave primarily the 9-iodo derivatives although the starting alkaloid was incompletely converted. Use of an excess of the reagents under the same conditions gave 9,11-diiodo derivatives in 72 and 76% yields. 9-Iodomethylcytisine was prepared (61% yield in two steps) by treatment of methylcytisine with an excess of NIS in trifluoroacetic acid followed by deiodination of the 9,11-diiodo derivative by Zn dust in a mixture of EtOH and aqueous HCl.

  在酸性溶液中，(–)-金雀花碱和甲基金雀花碱的 2-吡啶酮核心被一当量的 ICl 或 N-碘代琥珀酰亚胺 (NIS) 碘化，主要得到 9-碘衍生物，尽管起始生物碱未完全转化。在相同条件下使用过量的试剂得到9,11-二碘代衍生物，产率分别为72%和76%。 9-碘甲基金雀花碱的制备方法如下：在三氟乙酸中用过量的 NIS 处理甲基金雀花碱，然后在乙醇和 HCl 水溶液的混合物中用锌粉对 9,11-二碘代衍生物进行脱碘。
• Conjugates of 9- and 11-Halo-Substituted Cytisines with 1′-N-Methylurocanic Acid
  作者：P. R. Petrova、A. V. Koval’skaya、A. N. Lobov、I. P. Tsypysheva

  DOI：10.1007/s10600-019-02905-2

  日期：2019.11

  New (–)-cytisine derivatives were synthesized by conjugating 9- and 11-halo-substituted cytisines with 1′-N-methylurocanic acid using N-hydroxysuccinimide.

  通过使用 N-羟基琥珀酰亚胺将 9- 和 11-卤代取代的胞嘧啶与 1'-N-甲基尿烷酸结合，合成了新的 (-)-胞嘧啶衍生物。