Bis(propyl)-cognitin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: Bis(propyl)-cognitin
• 英文别名: bis(propyl)cognitin；B3C；bis (3)-cognitin；bis-tacrine；N,N'-bis(1,2,3,4-tetrahydroacridin-9-yl)propane-1,3-diamine
• 化学式: C₂₉H₃₂N₄
• 分子量: 436.6
• InChiKey: BHOCVLCAWPPEOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  49.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ammonium bicarbonate 生成 Bis(propyl)-cognitin
  参考文献：
  名称：

  Human insulin containing additional disulfide bonds

  摘要：

  本发明涉及含有额外二硫键的人类胰岛素及其制备方法。

  公开号：

  US08883722B2

文献信息

• Bistacrine derivatives as new potent antimalarials
  作者：Ines Schmidt、Gabriele Pradel、Ludmilla Sologub、Alexandra Golzmann、Che J. Ngwa、Anna Kucharski、Tanja Schirmeister、Ulrike Holzgrabe

  DOI：10.1016/j.bmc.2016.06.003

  日期：2016.8

  Linking two tacrine molecules results in a tremendous increase of activity against Plasmodia in comparison to the monomer. This finding prompted the synthesis of a library of monomeric and dimeric tacrine derivatives in order to derive structure–activity relationships. The most active compounds towards chloroquine sensitive Plasmodium strain 3D7 and chloroquine resistant strain Dd2 show IC50 values

  与单体相比，连接两个他克林分子导致抗疟原虫的活性大大增加。这一发现促进了单体和二聚他克林衍生物库的合成，以推导结构-活性关系。对氯喹敏感的疟原虫菌株3D7和对氯喹耐药的菌株Dd2最具活性的化合物在纳摩尔浓度范围内显示IC 50值，细胞毒性低，并靶向半胱氨酸蛋白酶falcipain-2，这对寄生虫的生长至关重要。
• Structure–Activity Relationship Studies of 9-Alkylamino-1,2,3,4-tetrahydroacridines against Leishmania (Leishmania) infantum Promastigotes
  作者：Carlos F. M. Silva、Teresa Leão、Filipa Dias、Ana M. Tomás、Diana C. G. A. Pinto、Eduardo F. T. Oliveira、Ana Oliveira、Pedro A. Fernandes、Artur M. S. Silva

  DOI：10.3390/pharmaceutics15020669

  日期：——

  Leishmaniasis is one of the most neglected diseases in modern times, mainly affecting people from developing countries of the tropics, subtropics and the Mediterranean basin, with approximately 350 million people considered at risk of developing this disease. The incidence of human leishmaniasis has increased over the past decades due to failing prevention and therapeutic measures—there are no vaccines and chemotherapy, which is problematic. Acridine derivatives constitute an interesting group of nitrogen-containing heterocyclic compounds associated with numerous bioactivities, with emphasis to their antileishmanial potential. The present work builds on computational studies focusing on a specific enzyme of the parasite, S-adenosylmethionine decarboxylase (AdoMet DC), with several 1,2,3,4-tetrahydro-acridines emerging as potential inhibitors, evidencing this scaffold as a promising building block for novel antileishmanial pharmaceuticals. Thus, several 1,2,3,4-tetrahydroacridine derivatives have been synthesized, their activity against Leishmania (Leishmania) infantum promastigotes evaluated and a structure–activity relationship (SAR) study was developed based on the results obtained. Even though the majority of the 1,2,3,4-tetrahydroacridines evaluated presented high levels of toxicity, the structural information gathered in this work allowed its application with another scaffold (quinoline), leading to the obtention of N1,N12-bis(7-chloroquinolin-4-yl)dodecane-1,12-diamine (12) as a promising novel antileishmanial agent (IC50 = 0.60 ± 0.11 μM, EC50 = 11.69 ± 3.96 μM and TI = 19.48).

  利什曼病是现代最被忽视的疾病之一，主要影响热带、亚热带和地中海盆地的发展中国家人群，约有3.5亿人可能患上该病。由于预防和治疗措施的失败，人类利什曼病的发病率在过去几十年中增加了，目前没有疫苗和化疗，这是一个问题。吖啶衍生物是一类氮杂环化合物，与众多生物活性相关，尤其是它们的抗利什曼病潜力。本研究基于对寄生虫酶S-腺苷甲硫氨酸脱羧酶（AdoMet DC）的计算研究，发现多种1,2,3,4-四氢-吖啶可能是潜在的抑制剂，表明该支架是新型抗利什曼病药物的有前途的构建块。因此，合成了多种1,2,3,4-四氢吖啶衍生物，评估了它们对利什曼原虫（利什曼原虫）幼虫的活性，并根据所得结果开展了结构-活性关系（SAR）研究。尽管大多数评估的1,2,3,4-四氢吖啶衍生物表现出高毒性，但本研究收集的结构信息使其可以与另一个支架（喹啉）结合使用，导致获得N1，N12-双（7-氯喹啉-4-基）十二烷基-1,12-二胺（12）作为有前途的新型抗利什曼病药物（IC50 = 0.60±0.11μM，EC50 = 11.69±3.96μM和TI = 19.48）。
• Search of antitubercular activities in tetrahydroacridines: Synthesis and biological evaluation
  作者：R.P. Tripathi、S.S. Verma、Jyoti Pandey、K.C. Agarwal、Vinita Chaturvedi、Y.K. Manju、A.K. Srivastva、A. Gaikwad、S. Sinha

  DOI：10.1016/j.bmcl.2006.07.025

  日期：2006.10

  A series of 9-substituted tetrahydroacridines were synthesized by nucleophilic substitution of chloro group with different nucleophiles in 9-chlorotetrahydroacridine (2). The latter could be obtained by POCl3 mediated cyclization of the intermediate enamine, which in turn, was prepared by acid catalyzed condensation of anthranilic acid and cyclohexanone. Most of the compounds on antitubercular evaluation against M. tuberculosis H37 Rv and H37 Ra strains exhibited potent activities with MIC 6.125-0.78 mu g/mL comparable to the standard drugs. (c) 2006 Elsevier Ltd. All rights reserved.
• US7655801B2
  申请人：——

  公开号：US7655801B2

  公开（公告）日：2010-02-02
• Human insulin containing additional disulfide bonds
  申请人：Hubalek Frantisek

  公开号：US08883722B2

  公开（公告）日：2014-11-11

  The present invention is related to human insulin containing additional disulfide bonds and methods of making such.

  本发明涉及含有额外二硫键的人类胰岛素及其制备方法。