4'-氨基甲基-4,5'，8-三甲基补骨脂素 | 64358-50-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 中文名称: 4'-氨基甲基-4,5'，8-三甲基补骨脂素
• 英文名称: 4'-aminomethyl-4,5',8-trimethylpsoralen
• 英文别名: 3-(Aminomethyl)-2,5,9-trimethyl-7H-furo[3,2-g]chromen-7-one；3-(aminomethyl)-2,5,9-trimethylfuro[3,2-g]chromen-7-one
• CAS: 64358-50-5
• 化学式: C₁₅H₁₅NO₃
• 分子量: 257.289
• InChiKey: WBIICVGYYRRURR-UHFFFAOYSA-N

物化性质

• 熔点：
  196-198°C
• 溶解度：
  H2O：1 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  65.5
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 安全说明：
  S26,S27,S36,S36/37/39,S45
• 危险类别码：
  R20/21/22,R34,R40
• 海关编码：
  2932999099
• 危险品运输编号：
  UN 1759 8/PG 2

制备方法与用途

氨基甲基三氧化aselene 是一种psoralen衍生物，可与DNA和RNA病毒，包括HIV-1，通过核酸交联后结合紫外线照射来失活。

反应信息

• 作为反应物：
  描述：

  4'-氨基甲基-4,5'，8-三甲基补骨脂素 在 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.25h， 生成 N-α-Fmoc-L-aspartic acid-β-(4'-(aminomethyl)-4,5',8-trimethylpsoralen)
  参考文献：
  名称：

  Chemical Conversion of a trans-Activation Responsive RNA-Binding Fragment of HIV-1 Tat Protein into a Site-Specific Crosslinking Agent

  摘要：

  Replication of human immunodeficiency virus type 1 (HIV-1) requires specific interactions of Tat protein with the trans-activation responsive (TAR) region of RNA, a 59-base stem-loop structure located at the 5'-end of all mRNAs. We have devised a new method based on psoralen photochemistry to identify a specific contact between a fragment of Tat protein (residues 42-72) and TAR RNA. We synthesized a 30-amino acid fragment containing the arginine-rich RNA-binding domain of Tat(42-72) and chemically attached a psoralen at the amino terminus. Upon near ultraviolet irradiation (360 nm), this synthetic psoralen-peptide cross-linked to a single site in the TAR RNA sequence. The RNA-protein complex was purified, and the cross-link site on TAR RNA was determined by chemical and primer extension analyses. Our results show that the amino terminus of Tat(42-72) contacts, or is close to, uridine 42 in the lower stem of TAR RNA. Such psoralen-peptide conjugates provide a new class of probes for sequence-specific protein-nucleic acid interactions and could be used to selectively control gene expression or to induce site-directed mutations.

  DOI：

  10.1021/ja00125a002
• 作为产物：
  描述：

  4,5‘,8-三甲基]补骨脂素 在 盐酸 、 potassium phtalimide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 4'-氨基甲基-4,5'，8-三甲基补骨脂素
  参考文献：
  名称：

  用于高效、多功能 miRNA-mRNA 交联的 miRNA 探针迷你文库的设计和应用

  摘要：

  MicroRNA 构成一类影响细胞内各种过程的内源性非编码 RNA。通过与目标信使 RNA 3' 非翻译区的部分互补位点进行碱基配对，microRNA 参与大多数人类蛋白质编码基因的转录后调控。它们的失调与许多病理过程和疾病有关。因此，深入了解 microRNA 的作用机制至关重要。在这里，我们提出了探针设计的新概念，以实现高效且与序列无关的 miRNA-mRNA 交联。新策略基于针对所选miRNA使用受控探针混合物，其中通过短的基于寡聚乙二醇的接头将trioxsalen部分引入所选胞苷的N 4 -位置。使用感兴趣的 microRNA 探针微型文库进行的体外光交联实验显示出不同的交联效率，证明了所提出方法的普遍适用性。

  DOI：

  10.1002/chem.202101171

文献信息

• Aminomethyl psoralens. Electrophilic substitution of hydroxymethylphthalimide on linear furocoumarins
  作者：Ned D. Heindel、Mridula Choudhuri、Joel Ressner、Natalie Foster

  DOI：10.1002/jhet.5570220119

  日期：1985.1

  A new synthetic route to aminomethylpsoralens, substituted on the furan-ring, has been developed by electrophilic substitution of N-hydroxymethylphthalimide and subsequent hydrazinolysis. Hydroxy and methoxy activating functions on the psoralens lead to multi-site substitution and the products of these phthalimido-methylations resist simple cleavage with hydrazine. The two-step introduction of a single

  通过亲电取代N-羟甲基邻苯二甲酰亚胺并随后进行肼解反应，已开发出一种新的合成路线，可合成呋喃环上的氨基甲基补骨脂素。补骨脂素上的羟基和甲氧基活化功能导致多位取代，这些邻苯二甲酰亚胺基甲基化产物抵抗肼的简单裂解。在仅包含甲基取代基的补骨脂素中，成功地将CH 2 NH 2基团分为两步引入是成功的。
• Psoralens aminomethylation
  申请人：Elder Pharmaceuticals, Inc.

  公开号：US04950770A1

  公开（公告）日：1990-08-21

  A direct, acid-catalyzed substitution reaction incorporates an N-phthalimidomethyl group on the 4' or 5' carbon of a psoralen in yields of 60-80% via the condensation of an N-hydroxymethylamide or phthalimide (e.g. N-hydroxymethylphthalimide) and an appropriately substituted psoralen. The phthalimide moiety is cleaved from the psoralen ring by treatment with hydrazine to give 60 to 70% yields of the aminomethylpsoralens.

  一种直接的、酸催化的取代反应将N-邻苯二甲酰亚甲基基团引入光敏剂的4'或5'碳上，收率为60-80%，通过N-羟甲基酰胺或邻苯二甲酰亚胺（例如N-羟甲基邻苯二甲酰亚胺）与适当取代的光敏剂的缩合来实现。邻苯二甲酰亚胺基团通过用肼处理从光敏剂环中裂解，得到60到70%的氨基甲基光敏剂收率。
• Method and devices for the removal of psoralens from blood products
  申请人：——

  公开号：US20020115585A1

  公开（公告）日：2002-08-22

  Method for removing a pathogen-inactivating compound such as psoralen from a biological fluid such as blood or a blood product. One such method involves treating a blood product which contains a nucleic acid-containing pathogen to be inactivated. This method includes adding a pathogen-inactivating compound such as psoralen to the blood product; irradiating the psoralen and the blood product to form a mixture comprising the blood product, free psoralen, and low molecular weight psoralen photoproducts; and contacting the mixture with a hypercrosslinked resin to remove at least substantially all of the free psoralen and the low molecular weight psoralen photoproducts. A hypercrosslinked resin in this method preferably eliminates a wetting step that a number of other types of resins require before being used to adsorb the pathogen inactivating compound.

  从生物液体（如血液或血液制品）中去除一种病原体灭活化合物（如紫荆素）的方法。其中一种方法涉及处理含有核酸病原体的血液制品以进行灭活。该方法包括向血液制品中添加病原体灭活化合物（如紫荆素）；照射紫荆素和血液制品以形成含有血液制品、游离紫荆素和低分子量紫荆素光产物的混合物；并将该混合物与超交联树脂接触，以去除至少几乎所有的游离紫荆素和低分子量紫荆素光产物。在该方法中，超交联树脂优选地消除了其他类型的树脂在用于吸附病原体灭活化合物之前需要进行的浸润步骤。
• METHODS AND SYSTEMS FOR TREATING CELL PROLIFERATION DISORDERS WITH PSORALEN DERIVATIVES
  申请人：Toone Eric

  公开号：US20100266621A1

  公开（公告）日：2010-10-21

  Psoralen compounds of Formula (I): wherein (N + Aryl) is a member selected from the group consisting of nitrogen containing aromatic heterocycles of formulae (i)-(iii): wherein Z is a group of formula: wherein R is C 1 -C 30 hydrocarbyl, which may be linear, branched or cyclic and contains from 1 to 15 carbon-carbon double bonds, which may be conjugated or unconjugated with one another or may include an aryl ring, and may contain one or more substituents; R 1 is hydrogen, aryl, heteroaryl, alkyl, cycloalkyl, heterocyclyl, alkenyl, alkynyl, alkene-aryl, alkene-heteroaryl, alkene-heterocyclyl, alkene-cycloalkyl, fused cycloalkylaryl, fused cycloalkylheteroaryl, fused heterocyclylaryl, fused heterocyclyheteroaryl, alkylene-fused cycloalkylaryl, alkylene-fused cycloalkylheteroaryl, alkylene-fused heterocyclylaryl, alkylene-fused heterocyclyheteroaryl; n is an integer from 1 to 8 and X is a pharmaceutically acceptable counter ion; and their use in methods for the treatment of a cell proliferation disorder in a subject, pharmaceutical compositions containing the psoralen derivatives, a kit for performing the method, and a method for causing an autovaccine effect in a subject using the method.

  公式（I）的植酸化合物：其中（N+Aryl）是从以下化学式（i）-（iii）组成的含氮芳香杂环中选择的成员：其中Z是以下化学式的一组：其中R是C1-C30烃基，可以是直链、支链或环状，并且含有1至15个碳-碳双键，这些双键可以共轭或非共轭地彼此连接，也可以包括芳香环，并且可能含有一个或多个取代基；R1是氢、芳基、杂环芳基、烷基、环烷基、杂环烷基、烯基、炔基、烯基芳基、烯基杂环芳基、烯基杂环烷基、烯基环烷基、融合环烷基芳基、融合环烷基杂环芳基、融合杂环烷基芳基、融合杂环烷基杂环芳基、烷基-融合环烷基芳基、烷基-融合环烷基杂环芳基、烷基-融合杂环烷基芳基、烷基-融合杂环烷基杂环芳基；n是1至8的整数，X是药用可接受的对离子；以及它们在治疗受体内细胞增殖紊乱的方法中的使用，含有植酸衍生物的药物组合物，用于执行该方法的工具包，以及利用该方法在受体中引起自身疫苗效应的方法。
• Process for the sterilization of biological compositions and the product thereby
  申请人：——

  公开号：US20020068267A1

  公开（公告）日：2002-06-06

  The present invention concerns the product produced by inactivating extracellular or intracellular pathogenic virus in a biological composition without incurring substantial disruption or inactivation of cells and without significant loss of labile proteins or other valuable biological components also contained therein, the inactivation process comprising subjecting said composition to a virucidally effective amount of irradiation in the presence of (a) a mixture of a compound that quenches type I photodynamic reactions and a compound that quenches type II photodynamic reactions or (b) a bifunctional compound that is capable of quenching both type I and type II reactions, to thereby inactivate said virus while retaining functionality of said composition. The composition is advantageously subjected to the irradiation and the mixture of compounds or bifunctional compound in the presence of an irradiation sensitizer. Moreover, the process can be advantageously combined with a different virucidal method to enhance virus inactivation.

  本发明涉及通过使生物组成物中的细胞外或细胞内病原病毒失活而不造成细胞的重大破坏或失活，并且不会显著损失其中包含的易降解蛋白质或其他有价值的生物组分的产品。失活过程包括将该组成物暴露于具有杀毒作用的辐射量，同时存在(a)一种淬灭I型光动力反应的化合物和一种淬灭II型光动力反应的化合物的混合物或(b)能够淬灭I型和II型反应的双功能化合物，以此失活病毒同时保留该组成物的功能性。该组成物有利地暴露于辐射和化合物混合物或双功能化合物的同时存在辐射敏化剂。此外，该过程可以有利地与另一种杀毒方法结合，以增强病毒失活效果。