N-acetyl-4-aminophenyl 4-(diethylamino)butyrate hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: N-acetyl-4-aminophenyl 4-(diethylamino)butyrate hydrochloride
• 英文别名: 4-acetylaminophenyl 4-diethylaminobutyrate hydrochloride；(4-Acetamidophenyl) 4-(diethylamino)butanoate;hydrochloride
• 化学式: C₁₆H₂₄N₂O₃*ClH
• 分子量: 328.839
• InChiKey: HKMVYCSJHLHARD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.09
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-(二乙基氨基)丁酸 、 对乙酰氨基酚 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以82.1%的产率得到N-acetyl-4-aminophenyl 4-(diethylamino)butyrate hydrochloride
  参考文献：
  名称：

  WO2008/29200

  摘要：

  公开号：

文献信息

• 非常に速い皮膚浸透率を有するアセトアミノフェン及び関連化合物の正荷電水溶性プロドラッグ
  申请人：テックフィールズ バイオケム カンパニー リミテッド

  公开号：JP2016006124A

  公开（公告）日：2016-01-14

  【課題】本発明は、アセトアミノフェン及び関連化合物の使用と関連する副作用を克服するためにある。【解決手段】式（１）で表されるアセトアミノフェン、アセトアミノサロール及び関連化合物の新規な正荷電プロドラッグを設計し、合成した。これらのプロドラッグの正に荷電されたアミノ基は、薬物の溶解性を大いに増大させるだけでなく、膜のホスファート頭基上の負電荷と結合し、プロドラッグを細胞質ゾルの中に押し込む。プロドラッグは、アセトアミノフェン、アセトアミノサロール及び関連化合物よりも〜１５０倍速く人の皮膚を通して拡散する。プロドラッグは、人又は動物におけるＮＳＡＩＡ治療可能な状態の治療に使用され、どんな種類の薬物治療のためにも経口投与だけでなく経皮投与でも医薬的に使用され、ＮＳＡＩＡのたいていの副作用を回避し得る。【選択図】図４

  This invention is intended to overcome the side effects associated with the use of acetaminophen and related compounds. A novel positively charged prodrug of acetaminophen, acetaminosalol, and related compounds represented by formula (1) is designed and synthesized. The positively charged amino group of these prodrugs not only greatly increases the solubility of the drug but also binds to the negative charges on the phosphate head groups of the membrane, pushing the prodrug into the cytosolic sol. The prodrugs diffuse through human skin approximately 1-150 times faster than acetaminophen, acetaminosalol, and related compounds. The prodrugs are used for the treatment of conditions treatable with NSAIDs in humans or animals, and are medically used for any type of drug therapy, not only orally but also transdermally, avoiding most of the side effects of NSAIDs.【Figure Selection】Figure 4
• Positively charged water-soluble prodrugs of acetaminophen and related compunds with very fast skin penetration rate
  申请人：Techfields Biochem Co. Ltd

  公开号：EP2746251A2

  公开（公告）日：2014-06-25

  The novel positively charged pro-drugs of acetaminophen, acetaminosalol, and related compounds in the general formula (1) 'Structure 1' were designed and synthesized. The positively charged amino groups of these pro-drugs not only largely increases the solubility of the drugs, 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 diffuses through human skin ∼150 times faster than does acetaminophen, acetaminosalol, and related compounds. It takes 1-2 hours for acetaminophen and acetaminosalol, and related compounds to reach the peak plasma level when they are taken orally, but these prodrugs only took about ∼50 minutes to reach the peak plasma level when they are taken transdermally. In plasma, more than 90% of these pro-drugs can be changed back to the parent drugs in a few minutes. The prodrugs can be used medicinally for treating any NSAIAs-treatable conditions in humans or animals. The prodrugs can be administered not only orally, but also transdermally for any kind of medical treatments and avoid most of the side effects of NSAIAs. Controlled transdermal administration systems of the prodrugs enables acetaminophen, acetaminosalol, and related compounds to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of acetaminophen, acetaminosalol, and related compounds. Another great benefit of transdermal administration of these pro-drugs is that administering medication, especially to children, will be much easier.

  我们设计并合成了带正电荷的新型对乙酰氨基酚原药、对乙酰氨基酚醇原药以及通式（1）"结构 1 "中的相关化合物。这些原药带正电荷的氨基不仅在很大程度上增加了药物的溶解度，还与膜上磷酸头基的负电荷结合，将原药推入细胞质。结果表明，原药在人体皮肤中的扩散速度比对乙酰氨基酚、对乙酰氨基酚醇和相关化合物快 150 倍。口服对乙酰氨基酚和对乙酰氨基酚醇及相关化合物需要 1-2 小时才能达到血浆峰值水平，而经皮服用这些原药只需要约 50 分钟就能达到血浆峰值水平。在血浆中，90% 以上的原药可在几分钟内变回母药。这些原药可用于治疗人类或动物的任何非甾体抗炎药物可治疗的疾病。原药不仅可以口服，还可以透皮给药，用于任何类型的医疗，并可避免非甾体抗炎药的大部分副作用。原药的可控透皮给药系统可使对乙酰氨基酚、对乙酰氨基酚醇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对乙酰氨基酚、对乙酰氨基酚醇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 composition and uses thereof
  申请人：Techfields Pharma Co., Ltd.

  公开号：US11135153B2

  公开（公告）日：2021-10-05

  The present invention relates to compositions and uses of novel high penetration compositions or high penetration prodrugs (HPP), in particular HPPs for 4-aminophenol derivatives, which are capable of crossing biological barriers with high penetration efficiency. The HPPs herein 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, due to the ability of penetrating biological barriers, the HPPs herein 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 herein can be administered to a subject through various administration routes. For example, the HPPs can be locally delivered to an action site of a condition with a high concentration due to their ability of penetrating biological barriers and thus obviate the need for a systematic administration. For another example, the HPPs herein can be systematically administer to a biological subject and enter the general circulation with a faster rate.

  本发明涉及新型高渗透组合物或高渗透原药（HPP）的组合物和用途，特别是 4-氨基苯酚衍生物的 HPPs，它们能够以高渗透效率穿过生物屏障。这些 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，因此能够像母体药物或代谢物那样对病症进行治疗。此外，由于 HPPs 能够穿透生物屏障，因此能够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受试者用药。例如，由于 HPPs 具有穿透生物屏障的能力，因此可将其高浓度地局部递送至病症的作用部位，从而无需系统给药。再比如，本制剂中的 HPPs 可以系统地给生物体给药，并以更快的速度进入血液循环。
• POSITIVELY CHARGED WATER-SOLUBLE PRODRUGS OF ACETAMINOPHEN AND RELATED COMPOUNDS WITH VERY FAST SKIN PENETRATION RATE
  申请人：Techfields Biochem Co. Ltd

  公开号：EP2061749A1

  公开（公告）日：2009-05-27
• HIGH PENETRATION COMPOSITION AND USES THEREOF
  申请人：Yu Chongxi

  公开号：US20090221703A1

  公开（公告）日：2009-09-03

  The present invention relates to compositions and uses of novel high penetration compositions or high penetration prodrugs (HPP), in particular HPPs for 4-aminophenol derivatives, which are capable of crossing biological barriers with high penetration efficiency. The HPPs herein 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, due to the ability of penetrating biological barriers, the HPPs herein 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 herein can be administered to a subject through various administration routes. For example, the HPPs can be locally delivered to an action site of a condition with a high concentration due to their ability of penetrating biological barriers and thus obviate the need for a systematic administration. For another example, the HPPs herein can be systematically administer to a biological subject and enter the general circulation with a faster rate.