3,5-dichlorocytisine | 40360-35-8

• 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: 3,5-dichlorocytisine
• 英文别名: Dichlorocytisine；(1R,5S)-9,11-Dichloro-1,2,3,4,5,6-hexahydro-1,5-methano-8H-pyrido[1,2-a][1,5]diazocin-8-one；(1R,9S)-3,5-dichloro-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one
• CAS: 40360-35-8
• 化学式: C₁₁H₁₂Cl₂N₂O
• 分子量: 259.135
• InChiKey: MBFUUTUPEKSDBX-NKWVEPMBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 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：

  4-O-hemisuccinylpodophyllotoxin 、 3,5-dichlorocytisine 在 4-二甲氨基吡啶 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  鬼臼毒素和胞嘧啶双化合物的杀虫活性

  摘要：

  探索基于天然产物杀虫剂候选，并且在农业天然植物的高附加值的应用，一系列双化合物从两个天然产物鬼臼毒素和野靛碱，这是从该植物中分离的制备鬼臼hexandrum和披针叶黄华分别. 化合物IIa (X = Cl，Y = R 1  = R 2  = H)、IIIc (X = Y = R 1  = R 2  = Cl) 和IVd (X = R 1  = R 2 = Br, Y = H) 显示鬼臼毒素对粘虫的 2 倍以上有效杀虫活性，FMR 大于 60%。还观察到 SAR。值得注意的是，首次提出了双杀虫剂的想法。我们希望这一想法将有助于设计新的双杀虫剂，为未来六味子和披针草作为潜在的植物性农药在农业中的高附加值应用奠定基础。

  DOI：

  10.1016/j.bmcl.2021.128104
• 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 1.5h， 以83%的产率得到3,5-dichlorocytisine
  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

• Cytisine-flavonoid conjugates: Synthesis and antitumor structure-activity relationship research
  作者：Renhao Liu、Xiaoze Bao、Xuanrong Sun、Yue Cai、Tianwei Zhang、Xinyi Ye、Xing-Nuo Li

  DOI：10.1016/j.tetlet.2020.151803

  日期：2020.4

  In research of anti-triple negative breast cancer (TNBC) agents, a series of cytisine-flavonoid conjugates (A-1∼G-1) were designed and synthesized in high yields with (-)-cytisine and flavonoids via N,N-4-dimethyl-4-aminopyridine (DMAP)-catalyzed synthetic strategy. In addition, the in vitro cytotoxicity of the conjugates was tested, and the results showed that some compounds had better cytotoxicity

  在抗三阴性乳腺癌（TNBC）剂的研究，一系列金雀花碱的类黄酮共轭物（的A-1~G-1 ）设计并以高产率合成了（ - ） -金雀花碱和黄酮类化合物经由N，N- - 4-二甲基-4-氨基吡啶（DMAP）催化的合成策略。另外，测试了缀合物的体外细胞毒性，结果表明某些化合物对人乳腺癌细胞（MDA-MB-231）的毒性比阳性对照药物紫杉醇更好。结构-活性关系的研究表明，以5-氯和黄酮类为特征的半胱氨酸形成的结合物对MDA-MB-231细胞具有更好的抗增殖作用。
• New 12-N-β-Hydroxyethylcytisine Derivatives with Potential Antiarrhythmic Activity
  作者：I. P. Tsypysheva、A. V. Koval’skaya、I. U. Khalilova、Yu. Yu. Bakhtina、R. Yu. Khisamutdinova、S. F. Gabdrakhmanova、A. N. Lobov、F. S. Zarudii、M. S. Yunusov

  DOI：10.1007/s10600-014-0945-5

  日期：2014.5

  12-N-β-Hydroxyethylcytisine derivatives containing Cl, Br, and nitro groups on the 2-pyridone core were synthesized. Their antiarrhythmic activity was studied in vivo.

  研究人员合成了在 2-吡啶酮核心上含有 Cl、Br 和硝基的 12-N-β-羟乙基胞嘧啶衍生物。在体内研究了它们的抗心律失常活性。
• Synthesis of <i>N</i>-Arylcytisine Derivatives Using the Copper-Catalyzed Chan-Lam Coupling
  作者：Oriel A. Sánchez-Velasco、Jorge Saavedra-Olavarría、Daniel A. A. Araya-Santelices、Patricio Hermosilla-Ibáñez、Bruce K. Cassels、Edwin G. Pérez

  DOI：10.1021/acs.jnatprod.1c00275

  日期：2021.7.23

  N-Arylcytisine derivatives are quite rare. We report here a practical methodology to obtain these compounds. Using the copper-catalyzed Chan-Lam coupling, we synthesized new N-arylcytisine derivatives at room temperature, in air and using inexpensive phenylboronic acids. Cytisine and 3,5-dihalocytisines can act as substrates, and among the products, the p-Br-derivative 2r was used as a substrate to

  N- Arylcytisine 衍生物非常罕见。我们在这里报告了一种获得这些化合物的实用方法。使用铜催化的 Chan-Lam 偶联，我们在室温、空气中和使用廉价的苯基硼酸合成了新的N-芳基胞嘧啶衍生物。Cytisine和3,5-dihalocytisines可以作为底物，在产物中，p - Br-衍生物2r作为底物在Pd偶联条件下得到联芳基衍生物；使用经典的碳二亚胺条件将酯2j转化为其酸和酰胺衍生物。这表明 Chan-Lam 交叉偶联反应可以作为天然产物衍生化的通用合成工具。
• 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。
• Alkylation of 9- and 11-Substituted and 9,11-Disubstituted (–)-Cytisine Derivatives by Dibromoethane
  作者：A. V. Koval’skaya、A. N. Lobov、V. A. Sorokina、I. P. Tsypysheva

  DOI：10.1007/s10600-023-04185-3

  日期：2023.9