5-Bromocytisine | 207390-16-7

• 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: 5-Bromocytisine
• 英文别名: (1R,9S)-3-bromo-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one
• CAS: 207390-16-7
• 化学式: C₁₁H₁₃BrN₂O
• 分子量: 269.141
• InChiKey: QGUJDQNVLMZXLT-JGVFFNPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 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：

  异氰酸苯酯 、 5-Bromocytisine 以 苯 为溶剂， 反应 1.0h， 以98%的产率得到(1R,5R)-11-bromo-8-oxo-N-phenyl-1,5,6,8-tetrahydro-2H-1,5-methanopyrido[1,2-a][1,5]diazocine-3(4H)-carboxamide
  参考文献：
  名称：

  喹唑啉生物碱 (-)-胞嘧啶的酰胺和羧酰胺对人流感病毒 A (H1N1) 和 3 型副流感病毒的抗病毒活性

  摘要：

  摘要 合成了喹唑啉生物碱 ( - )-胞嘧啶的新型衍生物。评估了 ADME 特性、对 HEK293 细胞的细胞毒性和对 A/California/07/09(H1N1)pdm09 病毒 (IAV) 和人类副流感病毒 3 (HPIV3) 病毒的活性。结果表明，甲基胞嘧啶的 9-甲酰胺（带有苯基和烯丙基脲的片段）是对 IAV 最具活性的化合物，这可能是由于计算机预测的它们与 IAV 神经氨酸酶的 4R7B 活性位点相互作用的特殊性。以这些尿素的CC 50 /IC 50之比计算的选择性指数(SI)相应地为47和59。还发现，从异氰酸烯丙酯和 ( -)-cytisine 或 9,11-dibromocytisine 能够抑制 HPIV3 的繁殖，SI = 58 和 95。此外，最后一种化合物 - (1  R ,5 R )- N -allyl-9,11-dibromo-8-oxo -1,5,6,8-tetrahydro-2

  DOI：

  10.1080/14786419.2019.1696791
• 作为产物：
  描述：

  cytisine 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 2.0h， 以27%的产率得到3-Bromocytisine
  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

• In vivo modulation of dopaminergic nigrostriatal pathways by cytisine derivatives: Implications for Parkinson's Disease
  作者：J. Andrés Abin-Carriquiry、Gustavo Costa、Jessika Urbanavicius、Bruce K. Cassels、Marco Rebolledo-Fuentes、Susan Wonnacott、Federico Dajas

  DOI：10.1016/j.ejphar.2008.05.013

  日期：2008.7

  Nicotinic acetylcholine receptor agonists are considered potential pharmacological agents for Parkinson's Disease treatment, due to their ability to improve experimental Parkinson symptomatology, reduce 3,4-dihydroxy-L-phenylalanine-incluced clyskinesias and stop the neurodegenerative process at an experimental level. In the present work, the ability of the nicotinic agonistcytisine and two halogenated derivatives (3-bromocytisine and 5-bromocytisine) to induce striatal dopamine release was characterized in vivo by microdialysis. Cytisine, 5-bromocytisine and nicotine were much more efficacious than 3-bromocytisine in eliciting dopamine release in response to their local application through the microdialysis probe. Moreover, the agonists were intermittently administered before and after an intranigral injection of 6-hydroxydopamine (6-OHDA), and striatal dopamine tissue levels were assessed 8 days after the lesion. Both cytisine and its 5-bromo derivative (but not the 3-bromo derivative) significantly prevented the decrease of striatal dopamine tissue levels induced by 6-OHDA. These results suggest that the efficacy of nicotinic agonists to stimulate dopamine release in vivo through presynaptic nicotinic receptors could be related to their potential to induce striatal protection. (C) 2008 Elsevier B.V. All rights reserved.