sodium 4-[bis(2-chloroethyl)amino]-N-acetyl-L-phenylalanine | 1016970-03-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: sodium 4-[bis(2-chloroethyl)amino]-N-acetyl-L-phenylalanine
• 英文别名: sodium;(2S)-2-acetamido-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoate
• CAS: 1016970-03-8
• 化学式: C₁₅H₁₉Cl₂N₂O₃*Na
• 分子量: 369.223
• InChiKey: RNQMNUOSXMSMSZ-UQKRIMTDSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.23
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  72.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  sodium 4-[bis(2-chloroethyl)amino]-N-acetyl-L-phenylalanine 、 2-二乙氨基-1-溴乙烷氢溴酸盐 以 乙腈 为溶剂， 反应 3.0h， 以72.1%的产率得到4-[bis(2-chloroethyl)amino]-N-acetyl-L-phenylalanine 2-(N,N-diethylamino)ethyl ester hydrobromide
  参考文献：
  名称：

  WO2008/41059

  摘要：

  公开号：

文献信息

• HIGH PENETRATION PRODRUG COMPOSITIONS OF MUSTARDS AND MUSTARD-RELATED COMPOUNDS
  申请人：Yu Chongxi

  公开号：US20100069336A1

  公开（公告）日：2010-03-18

  The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of mustards and mustard-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

  本发明提供了新型高渗透性组合物（HPC）或高渗透性前药（HPP）芥末及芥末相关化合物的组合物，其能够高效地穿过生物屏障。HPP能够在穿过生物屏障后转化为母体活性药物或药物代谢物，从而可以治疗母体药物或代谢物所能治疗的疾病。此外，HPP能够到达母体药物无法进入或无法在目标区域产生足够浓度的区域，从而提供新型治疗方法。HPP可以通过各种给药途径给予受试者，例如，局部给药于高浓度的病变部位或经系统给药于生物体内，并以更快的速率进入循环系统。
• Positively charged water-soluble prodrugs of mustards and related compounds with very high skin penetration rates
  申请人：Techfields Biochem Co. Ltd

  公开号：EP2792670A1

  公开（公告）日：2014-10-22

  The novel positively charged pro-drugs of mustards and related compounds in the general formula (1) 'Structure 1' were designed and synthesized. The compounds of the general formula (1) 'Structure 1' indicated above can be prepared from mustards and related compounds, by reaction with suitable alcohols, thiols, or amines and coupling reagents, such as N, N'-Dicyclohexylcarbodiimide, N, N'-Diisopropylcarbodiimide, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, onzotriazol-1-yl-oxy-tris (dimethylamino)phosphonium hexafluorophosphate, et al. The positively charged amino groups of these pro-drugs not only largely increases the solubility of the drugs in water, but also bonds to the negative charge on the phosphate head group of membranes and pushes the pro-drug into the cytosol. The results suggest that the pro-drugs diffuse through human skin ∼100 times faster than do mustards and related compounds. In plasma, more then 90% of these pro-drugs can change back to the parent drugs in a few minutes. The prodrugs can be used medicinally in treating any mustards and related compounds-treatable conditions in humans or animals. The prodrugs can be administered transdermally for any kind of medical treatments and avoid most of the side effects of mustards and related compounds. Controlled transdermal administration systems of the prodrug enables mustards and related compounds to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of mustards and related compounds. Another great benefit of transdermal administration of these pro-drugs is that administering medication, especially to children, will be much easier.

  设计并合成了通式（1）"结构 1 "中芥子及相关化合物的新型带正电荷原药。上述通式(1)'结构 1'的化合物可由芥子和相关化合物通过与合适的醇、硫醇或胺和偶联试剂（如 N, N'-Dicyclohexylcarbodiimide, N. N. N'-Diisopropylcarbodiimide, N. N. N'-Disopropylcarbodiimide）反应制备、N'-二异丙基碳二亚胺、O-(苯并三唑-1-基)-N,N,N',N'-四甲基脲四氟硼酸盐、O-(苯并三唑-1-基)-N,N,N',N'-四甲基脲六氟磷酸盐、偶氮三唑-1-基氧基-三（二甲基氨基）鏻六氟磷酸盐等。这些原药带正电荷的氨基不仅在很大程度上增加了药物在水中的溶解度，而且还与膜上磷酸头基的负电荷结合，将原药推入细胞质中。研究结果表明，原药在人体皮肤中的扩散速度比芥子和相关化合物快 100 倍。在血浆中，90%以上的原药可以在几分钟内变回母药。这些原药可用于治疗人或动物的任何芥子气及相关化合物可治疗的疾病。原药可以透皮给药，用于任何类型的医疗，并可避免芥子和相关化合物的大部分副作用。原药的可控透皮给药系统可使芥子剂和相关化合物不断达到最佳治疗血药浓度，从而提高疗效并减少芥子剂和相关化合物的副作用。这些原药透皮给药的另一大好处是，用药（尤其是给儿童用药）将变得更加容易。
• High penetration prodrug compositions of mustards and mustard-related compounds
  申请人：Yu Chongxi

  公开号：US10189774B2

  公开（公告）日：2019-01-29

  The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of mustards and mustard-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

  本发明提供了芥子和芥子相关化合物的新型高渗透组合物（HPC）或高渗透原药（HPP），它们能够以高渗透效率穿过生物屏障。HPPs 在穿过生物屏障后能够转化为母体活性药物或药物代谢物，因此能够提供母体药物或代谢物所能提供的病症治疗。此外，HPPs 还能到达母体药物可能无法到达的区域，或在目标区域产生足够的浓度，从而提供新的治疗方法。HPPs 可通过各种给药途径给药，例如，以高浓度局部给药到疾病的作用部位，或系统地给药到生物体内，以更快的速度进入血液循环。
• POSITIVELY CHARGED WATER-SOLUBLE PRODRUGS OF MUSTARDS AND RELATED COMPOUNDS WITH VERY HIGH SKIN PENETRATION RATES
  申请人：Techfields Biochem Co. Ltd

  公开号：EP2077991A1

  公开（公告）日：2009-07-15
• [EN] POSITIVELY CHARGED WATER-SOLUBLE PRODRUGS OF MUSTARDS AND RELATED COMPOUNDS WITH VERY HIGH SKIN PENETRATION RATES<br/>[FR] PROMÉDICAMENTS DE MOUTARDES HYDROSOLUBLES À CHARGE POSITIVE ET COMPOSÉS APPARENTÉS PRÉSENTANT DES TAUX DE PÉNÉTRATION CUTANÉE TRÈS ÉLEVÉS
  申请人：TECHFIELDS BIOCHEM CO LTD

  公开号：WO2008041059A1

  公开（公告）日：2008-04-10

  [EN] The novel positively charged pro-drugs of mustards and related compounds in the general formula (1) 'Structure 1' were designed and synthesized. The compounds of the general formula (1) 'Structure 1' indicated above can be prepared from mustards and related compounds , by reaction with suitable alcohols, thiols, or amines and coupling reagents, such as N, N'-Dicyclohexylcarbodiimide, N, N'-Diisopropylcarbodiimide, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, Benzotriazol-1-yl-oxy-tris (dimethylamino)phosphonium hexafluorophosphate, et al. The positively charged amino groups of these pro-drugs not only largely increases the solubility of the drugs in water, but also bonds to the negative charge on the phosphate head group of membranes and pushes the pro-drug into the cytosol. The results suggest that the pro-drugs diffuse through human skin ~100 times faster than do mustards and related compounds. In plasma, more than 90% of these pro-drugs can change back to the parent drugs in a few minutes. The prodrugs can be used medicinally in treating any mustards and related compounds-treatable conditions in humans or animals. The prodrugs can be administered transdermally for any kind of medical treatments and avoid most of the side effects of mustards and related compounds. Controlled transdermal administration systems of the prodrug enables mustards and related compounds to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of mustards and related compounds. Another great benefit of transdermal administration of these pro-drugs is that administering medication, especially to children, will be much easier.
  [FR] L'invention concerne la conception et la synthèse de nouveaux promédicaments de moutardes à charge positive et des composés apparentés représentés par la formule générale (1) = Structure 1 =. ilest possible de préparer les composés représentés par la formule générale (1) = Structure 1 = mentionnés ci-dessus à partir de moutardes et de composés apparentés, par réaction avec des alcools, des thiols ou des amines appropriés et des réactifs de couplage appropriés, tels que N, N'-Dicyclohexylcarbodiimide, N, N'-Diisopropylcarbodiimide, O-(Benzotriazol-1-yl)-N,N,N',N'-tétraméthyluronium tétrafluoroborate, O-(Benzotriazol-1-yl)-N,N,N',N'-tétraméthyluronium hexafluorophosphate, Benzotriazol-1-yl-oxy-tris (diméthylamino)phosphonium hexafluorophosphate, et al. Non seulement les groupes amino à charge positive de ces promédicaments augmentent considérablement l'hydrosolubilité des médicaments, mais ils se lient également à la charge négative sur le groupe de tête phosphatique de membranes et poussent le promédicament vers le cytosol. Les résultats suggèrent que les promédicaments se diffusent via la peau humaine ~100 fois plus vite que les moutardes et composés apparentés. Dans le plasma, plus de 90 % de ces promédicaments peuvent redonner le médicament en quelques minutes. Les promédicaments peuvent être utilisés médicalement dans le traitement de n'importe quel trouble pouvant être traité par les moutardes et les composés apparentés chez l'homme ou chez l'animal. On peut administrer les promédicaments par voie transdermique pour tout type de traitement médical, et éviter ainsi la plupart des effets secondaires des moutardes et des composés apparentés. Des systèmes d'administration par voie transdermique contrôlée dudit promédicament permettent aux moutardes et aux composés apparentés d'atteindre de manière constante des concentrations sanguines thérapeutiques optimales, afin d'améliorer l'efficacité et de réduire les effets secondaires des moutardes et composés apparentés. Un autre avantage important lié à l'administration transdermique de ces promédicaments est que celle-ci facilite grandement l'administration du médicament, particulièrement chez les enfants.