(1-{[4-(6-chloro-2-methoxy-acridin-9-ylamino)-butyl]-[3-(6-chloro-2-methoxy-acridin-9-ylamino)-propyl]-carbamoyl}-ethyl)-carbamic acid tert-butyl ester

• 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: (1-{[4-(6-chloro-2-methoxy-acridin-9-ylamino)-butyl]-[3-(6-chloro-2-methoxy-acridin-9-ylamino)-propyl]-carbamoyl}-ethyl)-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[1-[4-[(6-chloro-2-methoxyacridin-9-yl)amino]butyl-[3-[(6-chloro-2-methoxyacridin-9-yl)amino]propyl]amino]-1-oxopropan-2-yl]carbamate
• 化学式: C₄₃H₄₈Cl₂N₆O₅
• 分子量: 799.797
• InChiKey: VNZBWLPJJMSMAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.7
• 重原子数：
  56
• 可旋转键数：
  17
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  亚精胺 在 potassium carbonate 、 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (1-{[4-(6-chloro-2-methoxy-acridin-9-ylamino)-butyl]-[3-(6-chloro-2-methoxy-acridin-9-ylamino)-propyl]-carbamoyl}-ethyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Antimalarial, Antitrypanosomal, and Antileishmanial Activities and Cytotoxicity of Bis(9-amino-6-chloro-2-methoxyacridines):  Influence of the Linker

  摘要：

  Forty bis(9-amino-6-chloro-2-methoxyacridines), in which acridine moieties are joined by alkanediamines, polyamines, or polyamines substituted by a side chain, were synthesized and tested for their in vitro activity upon the erythrocytic stage of Plasmodium falciparum, trypomastigote stage of Trypanosoma brucei, and amastigote stage of Trypanosoma cruzi and Leishmania infantum as well as for their cytotoxic effects upon MRC-5 cells. Results clearly showed the importance of the nature of the linker and of its side chain for antiparasitic activity, cytotoxicity, and cellular localization. Among several compounds devoid of cytotoxic effects at 25 mu M upon MRC-5 cells, one displayed IC50 values ranging from 8 to 18 nM against different P. falciparum strains while three others totally inhibited T. brucei at 1.56 mu M.

  DOI：

  10.1021/jm990946n

文献信息

• Chloroquine coupled nucleic acids and methods for their synthesis
  申请人：Kosak M. Kenneth

  公开号：US20060040879A1

  公开（公告）日：2006-02-23

  This invention discloses compositions and methods for preparing chloroquine-coupled nucleic acid compositions. The prior art has shown that chloroquines given as free drug in high enough concentration, enhances the release of various agents from cellular endosomes into the cytoplasm. The purpose of these compositions is to provide a controlled amount of chloroquine at the same site where the nucleic acid needs to be released, thereby reducing the overall dosage needed. The compositions comprise a chloroquine substance coupled to a nucleic acid directly or through a variety of pharmaceutical carrier substances. The carrier substances include polysaccharides, synthetic polymers, proteins, micelles and other substances for carrying and releasing the chloroquine compositions in the body for therapeutic effect. The compositions can also include a biocleavable linkage for carrying and releasing nucleic acids for therapeutic or other medical uses. The invention also discloses nucleic acid carrier compositions that are coupled to targeting molecules for targeting the delivery of nucleic acids to their site of action.

  本发明披露了制备氯喹偶联核酸组合物的组成和方法。先前的研究表明，以足够高的浓度给予氯喹作为自由药物，可以增强细胞内体内各种物质从内体泡中释放到细胞质中。这些组合物的目的是在核酸需要释放的同一位置提供受控量的氯喹，从而降低所需的总剂量。该组合物包括直接或通过各种药物载体物质偶联的氯喹物质和核酸。载体物质包括多糖、合成聚合物、蛋白质、胶束和其他用于在体内携带和释放氯喹组合物以达到治疗效果的物质。该组合物还可以包括生物可降解连接来携带和释放用于治疗或其他医疗用途的核酸。本发明还披露了偶联到靶向分子的核酸载体组合物，用于将核酸传递到其作用位置。
• Cyclic bis-compounds clearing malformed proteins
  申请人：The Regents of the University of California

  公开号：US20040229898A1

  公开（公告）日：2004-11-18

  The invention is drawn to compositions and methods for inhibiting and treating malformed forms of proteins causing neurodegenerative disease, such as protease resistant prion proteins (PrP Sc ) and those associated with transmissible spongiform encephalopathies (TSEs). Bis-acridines are characterized by a dimeric motif, comprising two acridine heterocycles tethered by a linker. A library of bis-(6-chloro-2-methoxy-acridin-9-yl) and bis-(7-chloro-2-methoxy-benzo[b][1,5]naphthyridin-10-yl) analogs were synthesized to explore the effect of structurally diverse linkers on PrP Sc replication in ScN2a cells. Structure-activity analysis revealed that linker length and structure effect inhibition of prion replication in cultured, scrapied cells. Three bis-acridine analogs, (6-chloro-2-methoxy-acridin-9-yl)-(3-{4-[3-(6-chloro-2-methoxy-acridin-9-ylamino)-propyl]-piperazin-1-yl}-propyl)-amine, N,N′-bis-(6-chloro-2-methoxy-acridin-9-yl)-1,8-diamino-3,6-dioxaoctane, and (1-{[4-(6-chloro-2-methoxy-acridin-9-ylamino)-butyl]-[3-(6-chloro-2-methoxy-acridin-9-ylamino)-propyl]-carbamoyl}-ethyl)-carbamic acid tert-butyl ester, showed half-maximal inhibition of PrP Sc formation at effective concentrations (EC 50 ) of 40 nM, 25 nM and 30 nM, respectively, and were not cytotoxic for uninfected neuroblastoma cells at concentrations of 500 nM. The data produced here shows that bis-acridine analogs prevent or slow PrP Sc replication.

  本发明涉及用于抑制和治疗导致神经退行性疾病的畸形形式蛋白质的组合物和方法，例如抗蛋白酶朊病毒蛋白（PrP Sc ）以及与传染性海绵状脑病（TSE）相关的蛋白。双吖啶的特点是具有二聚体结构，由两个吖啶杂环通过连接体拴在一起。我们合成了双(6-氯-2-甲氧基-吖啶-9-基)和双(7-氯-2-甲氧基-苯并[b][1,5]萘啶-10-基)类似物库，以探讨结构不同的连接体对 PrP Sc 在 ScN2a 细胞中复制的影响。结构-活性分析表明，连接体的长度和结构对朊病毒在培养的刮伤细胞中的复制有抑制作用。三种双吖啶类似物：(6-氯-2-甲氧基-吖啶-9-基)-(3-{4-[3-(6-氯-2-甲氧基-吖啶-9-基氨基)-丙基&rsqb；-哌嗪-1-基}-丙基)-胺、N,N′-双-(6-氯-2-甲氧基-吖啶-9-基)-1,8-二氨基-3,6-二氧杂辛烷和(1-&lcub；N′-双-(6-氯-2-甲氧基-吖啶-9-基)-1,8-二氨基-3,6-二氧杂辛烷和 (1-氨基甲酰基}-乙基)-氨基甲酸叔丁酯对 PrP Sc 形成的有效浓度（EC 50 分别为 40 nM、25 nM 和 30 nM，对未感染的神经母细胞瘤细胞无细胞毒性。这里的数据表明，双吖啶类似物能阻止或减缓 PrP Sc 复制。
• Nucleic acid carrier compositions and methods for their synthesis
  申请人：Kosak M. Kenneth

  公开号：US20050153913A1

  公开（公告）日：2005-07-14

  This invention discloses compositions and methods for preparing pharmaceutical nucleic acid carriers. The compositions comprise a carrier substance coupled to a nucleic acid intercalator whereby the intercalator is coupled by intercalation to the nucleic acid. The compositions can also include a biocleavable linkage for carrying and releasing nucleic acids for therapeutic or other medical uses. The invention also discloses nucleic acid carrier compositions that are coupled to targeting molecules for targeting the delivery of nucleic acids to their site of action.

  本发明公开了制备药物核酸载体的组合物和方法。这些组合物包括与核酸插层物耦合的载体物质，其中插层物通过插层与核酸耦合。这些组合物还可以包括生物可裂解连接，用于携带和释放核酸，以用于治疗或其他医疗用途。本发明还公开了与靶向分子偶联的核酸载体组合物，用于将核酸靶向递送至其作用位点。
• Chloroquine drug compositions and methods for their synthesis
  申请人：Kosak Kenneth M.

  公开号：US20080051323A1

  公开（公告）日：2008-02-28

  This invention discloses compositions of chloroquine-coupled active agents, including methods for their preparation. The prior art has shown that chloroquines given as free drug in high enough concentration, enhances the release of various agents from cellular endosomes into the cytoplasm. The purpose of these compositions is to provide a controlled amount of chloroquine at the same site where the active agent is delivered, thereby reducing the overall dosage needed. The compositions comprise a chloroquine substance coupled to an active agent directly or through a variety of pharmaceutical carrier substances. The carrier substances include polysaccharides, synthetic polymers, proteins, micelles and other substances for carrying and releasing the chloroquine compositions in the body for therapeutic effect. The compositions can also include a biocleavable linkage for carrying and releasing active agents for therapeutic or other medical uses. The invention also discloses carrier compositions that are coupled to targeting molecules for targeting the delivery of chloroquine substances and active agents to their site of action.
• PROTECTED ANTIBODY-DRUG AND APTAMER-DRUG CONJUGATES
  申请人：Kosak Kenneth Michael

  公开号：US20210198671A1

  公开（公告）日：2021-07-01

  This is a Continuation in Part (CIP), and Nonprovisional U.S. Patent Application of Provisional U.S. Patent Application No. 62/786,340, filed Dec. 29, 2018, (herein called App. 62/786,340), the entire contents, including suitable methods and examples, and references therein which are hereby incorporated by reference as if fully set forth herein. All patent applications, patents, and publications, including supplementary materials, and additional references therein, that are cited herein, are hereby incorporated herein by reference in their entireties, except for any conflicting definitions, subject matter disclaimers or disavowals, and except to the extent that the incorporated material is inconsistent or in conflict with the express disclosures herein, in which case the language in this disclosure controls. For this invention, certain useful compositions and synthesis methods, and all categories of active agents, ligands, all intercalators of nucleic acids and peptides, any antibodies, any nucleic acids, including carrier nucleic acid compositions, peptide nucleic acids (PNA) and derivatized nucleic acids, splicing RNA (spRNA), DNAzymes, any polymers, targeting moieties, target substances including cancer cells, disease microorganisms and biomarkers, coupling agents and functional groups, are all suitably modified as needed. All compositions that would be useful for this invention after suitable modification, defined herein, including crRNAs, sgRNAs, any CRISPR proteins and compositions, any zinc finger proteins and compositions, any TALEN proteins and compositions and any suitable derivatives thereof.