trithiocarbonic acid 1-cyano-1-methyl-3-[2-(pyridin-2-yldisulfanyl)ethylcarbamoyl]propyl ester ethyl ester | 1195771-66-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: trithiocarbonic acid 1-cyano-1-methyl-3-[2-(pyridin-2-yldisulfanyl)ethylcarbamoyl]propyl ester ethyl ester
• 英文别名: PyrECT；4-cyano-4-ethylsulfanylcarbothioylsulfanyl-N-[2-(pyridin-2-yldisulfanyl)ethyl]pentanamide
• CAS: 1195771-66-4
• 化学式: C₁₆H₂₁N₃OS₅
• 分子量: 431.692
• InChiKey: QFGSYGYDGZOQOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  199
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  trithiocarbonic acid 1-cyano-1-methyl-3-[2-(pyridin-2-yldisulfanyl)ethylcarbamoyl]propyl ester ethyl ester 、 在 sodium carbonate 作用下， 以 甲醇 为溶剂， 以60%的产率得到(1⁴S,3³S,10E,12E,14R)-8⁶-chloro-1⁴-hydroxy-8⁵,1⁴-dimethoxy-3³,2,7,10-tetramethyl-1²,6-dioxo-7-aza-1(6,4)-oxazinana-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-4-yl 6-cyano-6,15,15,19,20-pentamethyl-9,18-dioxo-4-thioxo-3,5,13,14-tetrathia-10,19-diazahenicosan-21-oate
  参考文献：
  名称：

  [EN] POLYMER DERIVATIVES OF MERTANSINE AND THERAPEUTIC USES THEREOF
  [FR] DÉRIVÉS POLYMÈRES DE MERTANSINE ET LEURS UTILISATIONS THÉRAPEUTIQUES

  摘要：

  The present invention relates to polymer derivatives of mertansine (DM1) or of analogues thereof (e.g., DM4), preferably to polyacrylamide derivatives, of formula (A), or a pharmaceutically acceptable salt and/or solvate thereof, wherein m is 0 or 1, L is a linker, M is a hydrophilic polymeric moiety selected from polyacrylamide, polyacrylic acid, poly(N-(2-hydroxypropyl)methacrylamide), poly(oligo(ethylene glycol)methyl ether methacrylate), poly(2-methacryloxyethyl phosphorylcholine), and copolymers thereof, and RA is a terminal group, as defined in the application. The mertansine polymer derivatives of the invention are useful in the treatment of cancers. The invention also relates to a manufacturing process of the mertansine polymer derivatives.

  公开号：

  WO2022263627A1
• 作为产物：
  描述：

  2,2'-二硫二吡啶 在 溶剂黄146 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 2.0h， 生成 trithiocarbonic acid 1-cyano-1-methyl-3-[2-(pyridin-2-yldisulfanyl)ethylcarbamoyl]propyl ester ethyl ester
  参考文献：
  名称：

  Intracellular Delivery of a Proapoptotic Peptide via Conjugation to a RAFT Synthesized Endosomolytic Polymer

  摘要：

  Peptides derived from the third B-cell lymphoma 2 (Bcl-2) homology domain (BH3) can heterodimerize with antiapoptotic Bcl-2 family members to block their activity and trigger apoptosis. Use of these peptides presents a viable anticancer approach, but delivery barriers limit the broad application of intracellular-acting peptides as clinical therapeutics. Here, a novel diblock copolymer carrier is described that confers desirable pharmaceutical properties to intracellular-acting therapeutic peptides through site-specific molecular conjugation. This polymer was prepared using reversible addition-fragmentation chain transfer (RAFT) to form a pyridyl disulfide end-functionalized, modular diblock copolymer with precisely controlled molecular weight (M-n) and low polydispersity (PDI). The diblock polymer (M-n 19,000 g/mol, PDI 1.27) was composed of an N-(2-hydroxypropyl) methacrylamide (HPMA) first block (M-n 13,800 g/mol, PDI 1.13) intended to enhance water solubility and circulation time. The second polymer block was a pH-responsive composition designed to enhance endosomal escape and consisted of equimolar quantities of dimethylaminoethyl methacrylate (DMAEMA), propylacrylic acid (PM), and butyl methacrylate (BMA). A hemolysis assay indicated that the diblock polymer undergoes a physiologically relevant pH-dependent switch from a membrane inert (1% hemolysis, pH 7.4) to a membrane disruptive (61% hemolysis, pH 5.8) conformation. Thiol-disulfide exchange reactions were found to efficiently produce reversible polymer conjugates (75 mol % peptide reactivity with polymer) with a cell-internalized proapoptotic peptide. Microscopy studies showed that peptide delivered via polymer conjugates effectively escaped endosomes and achieved diffusion into the cytosol. Peptide-polymer conjugates also produced significantly increased apoptotic activity over peptide alone in HeLa cervical carcinoma cells as found using flow cytometric measurements of mitochondrial membrane depolarization (2.5-fold increase) and cell viability tests that showed 50% cytotoxicity after 6 h of treatment with 10 mu M peptide conjugate. These results indicate that this multifunctional carrier shows significant promise for proapoptotic peptide cancer therapeutics and also as a general platform for delivery of peptide drugs with intracellular targets.

  DOI：

  10.1021/mp9002267

文献信息

• TARGETED POLYMER BIOCONJUGATES
  申请人：Johnson Paul H.

  公开号：US20110129921A1

  公开（公告）日：2011-06-02

  Polymer bioconjugate having a RNAi agent covalently coupled to the alpha or omega end of a pH-dependent membrane-destabilizing polymer.

  具有RNAi剂共价耦合到pH依赖的膜破坏聚合物的α或ω端的聚合物生物偶联物。
• Diblock copolymers and polynucleotide complexes thereof for delivery into cells
  申请人：University of Washington

  公开号：EP2620161A1

  公开（公告）日：2013-07-31

  Described herein are copolymers, and methods of making and utilizing such copolymers. Such copolymers have at least two blocks: a first block that has at least one unit that is hydrophilic at physiologic pH, and a second block that has hydrophobic groups. This second block further has at least one unit with a group that is anionic at about physiologic pH. The described copolymers are disruptive of a cellular membrane including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the copolymer is endosomolytic.

  本文描述的是共聚物以及制造和利用这种共聚物的方法。此类共聚物至少有两个嵌段：第一嵌段至少有一个单元在生理 pH 值下具有亲水性，第二嵌段具有疏水基团。第二嵌段至少还有一个单元带有在生理 pH 值下为阴离子的基团。所述共聚物可破坏细胞膜，包括细胞外膜、细胞内膜、囊泡、细胞器、内体、脂质体或红细胞。优选地，在某些情况下，共聚物会破坏膜并进入细胞内环境。在具体例子中，共聚物具有内溶解作用。
• DIBLOCK COPOLYMERS AND POLYNUCLEOTIDE COMPLEXES THEREOF FOR DELIVERY INTO CELLS
  申请人：University of Washington

  公开号：EP2281011B1

  公开（公告）日：2013-02-27
• BISPECIFIC INTRACELLULAR DELIVERY VEHICLES
  申请人：Stayton Patrick S.

  公开号：US20110281354A1

  公开（公告）日：2011-11-17

  A composition for delivering an agent to a cell, comprising a bispecific affinity reagent and a pH-responsive, membrane destabilizing polymer. The bispecific affinity reagent may include a first affinity reagent covalently linked to a second affinity reagent, wherein the first affinity reagent binds to a molecule on the surface of a cell, and the second affinity reagent binds to an intracellular target.
• US8822213B2
  申请人：——

  公开号：US8822213B2

  公开（公告）日：2014-09-02