Cinchonine dihydrochloride | 24302-67-8

• 物质功能分类: 医药中间体 - 杂环化合物 - 喹啉类化合物
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 金鸡纳生物碱
• 英文名称: Cinchonine dihydrochloride
• 英文别名: (S)-[(2R,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-quinolin-4-ylmethanol;dihydrochloride
• CAS: 24302-67-8；524-55-0
• 化学式: C19H24Cl2N2O
• 分子量: 367.3
• InChiKey: ZDBQDNUZNQOCTH-OPMVAYRNSA-N

物化性质

• 熔点：
  179 °C

计算性质

• 辛醇/水分配系数(LogP)：
  4.01
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  36.4
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 安全说明：
  S24/25,S26,S61
• 海关编码：
  29339900
• 危险品标志：
  Xi,N
• WGK Germany：
  1
• RTECS号：
  OF0700000
• 危险类别码：
  R51/53,R41,R37/38
• 危险品运输编号：
  UN 3077 9/PG 3

制备方法与用途

药理作用

辛可尼丁对肿瘤细胞生长的影响：辛可尼丁能够抑制肿瘤细胞的增殖，并促进其早期凋亡。同时，它还能增强促进细胞凋亡因子的表达，抑制抑制凋亡因子的表达。

制备

在大气压下蒸馏出约80%的溶剂体积后，加入190毫升乙酸乙酯并将有机溶液用2摩尔/升的盐酸水溶液（114毫升）清洗。得到的乙酸乙酯溶液于60℃加到55.94克（0.19摩尔）辛可尼丁的乙腈（760毫升）悬浮液中。将生成的混合物在60℃搅拌10分钟后冷却至22℃，然后过滤。从1500毫升异丙醇中重结晶固体，并干燥后得到白色固体辛可尼丁二盐酸盐，总产率为29%。

文献信息

• Synthetic cinchona alkaloids against cancer
  申请人：Ares Pharmaceuticals, LLC

  公开号：US11066421B1

  公开（公告）日：2021-07-20

  Novel cinchona alkaloid compounds have been synthesized and discovered to have potent cytotoxic activity against cancer cells both in vitro and in vivo. Cinchona alkaloids, including trimeric cinchona alkaloids as well as their polymers can be used as catalysts of complex chemical reactions in organic chemistry, for example for the enantioselective desymmetrization of cyclic anhydrides, asymmetric synthesis of amino acids (Ayyanar Siva, Eagambaram Murugan. Synthesis 2005; 17:2927-2933; Hyeung-geun Park et al. Tetrahedron Letters, Volume 42, Issue 28, 2001, Pages 4645-4648; Shohei Takata et al., RSC Adv., 2016, 6, 72300-72305; Masud Parvez et al., Macromolecules 2014, 47, 6, 1922-1928; Marcelli, T. 2007, UvA-DARE (Digital Academic Repository). https://pure.uva.nl/ws/files/4416997/52576_marcelli_thesis.pdf Compounds described herein exhibit broad-spectrum therapeutic efficacy against different cancer types, including leukemias/lymphomas, prostate cancer, breast cancer, malignant melanoma, aggressive brain tumor/glioblastoma multiforme (GBM), non-small cell lung cancer. The chemical structure of the compounds includes a trimeric cinchona alkaloid and derivatives containing various groups attached in their structure.

  已合成新型金鸡纳生物碱化合物，并发现其在体内外对癌细胞具有强效的细胞毒活性。金鸡纳生物碱包括三聚金鸡纳生物碱以及它们的聚合物，可用作有机化学中复杂化学反应的催化剂，例如对环酐的对映选择性去对称化，氨基酸的不对称合成等。这些化合物对白血病/淋巴瘤、前列腺癌、乳腺癌、恶性黑色素瘤、侵袭性脑瘤/胶质母细胞瘤（GBM）、非小细胞肺癌等不同类型的癌症表现出广谱的治疗效果。这些化合物的化学结构包括三聚金鸡纳生物碱及其衍生物，含有各种连接在其结构中的基团。
• PHARMACEUTICAL COMPOSITIONS CONTAINING CINCHONINE DICHLORHYDRATE
  申请人：——

  公开号：US20020091136A1

  公开（公告）日：2002-07-11

  The invention relates to pharmaceutical compositions containing cinchonine dihydrochloride as active ingredient with a purity of at least 95%. The invention also relates to a process for preparing cinchonine dihydrochloride from cinchonine and the use of pharmaceutical compositions containing cinchonine dihydrochloride for treating multiple drug resistance.

  本发明涉及含有金鸡纳二盐酸盐的药物组合物，其活性成分的纯度至少为 95%。 本发明还涉及一种从金鸡纳树碱制备盐酸金鸡纳树碱的工艺，以及使用含有盐酸金鸡纳树碱的药物组合物治疗多重耐药性。
• COMPOSITIONS PHARMACEUTIQUES CONTENANT DU DICHLORHYDRATE DE CINCHONINE
  申请人：DEBIOPHARM S.A.

  公开号：EP0986390B1

  公开（公告）日：2002-09-25
• SYNTHETIC DIMERIC CINCHONA ALKALOIDS AGAINST CANCER
  申请人：Ares Pharmaceuticals, LLC

  公开号：US20220372029A1

  公开（公告）日：2022-11-24

  Synthetic, novel dimeric cinchona alkaloid compounds having potent cytotoxic activity against human cancer cells. The compounds are effective agents for inhibiting cellular proliferation, for example, in cancer cells. The compounds cause apoptotic cell death in and cause inhibition of clonogenic growth of human breast cancer, prostate cancer, leukemia, lymphoma cells at nanomolar concentrations. The chemical structure of the compound includes dimeric cinchona alkaloid and derivatives containing various groups attached in their structure. The compounds also possess hydroxy group functionality in the structure to enable the preparation of pharmaceutically applicable salts to enhance their solubility for ease of systemic administration in animals and in humans, for example, in cancer patients.
• US6528524B2
  申请人：——

  公开号：US6528524B2

  公开（公告）日：2003-03-04