3-Chlorocytisine | 444808-57-5

• 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-Chlorocytisine
• 英文别名: (1R,5S)-9-Chloro-1,2,3,4,5,6-hexahydro-1,5-methano-8H-pyrido[1,2-a][1,5]diazocin-8-one；(1R,9S)-5-chloro-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one
• CAS: 444808-57-5
• 化学式: C₁₁H₁₃ClN₂O
• 分子量: 224.69
• InChiKey: NBGMTBMAENFSAW-JGVFFNPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 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

• 作为产物：
  描述：

  cytisine 在 N-氯代丁二酰亚胺 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 1.0h， 以40%的产率得到3-Chlorocytisine
  参考文献：
  名称：

  Syntheses and evaluation of halogenated cytisine derivatives and of bioisosteric thiocytisine as potent and selective nAChR ligands

  摘要：

  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.

  DOI：

  10.1016/s0223-5234(01)01222-3

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.