2-[(2,6-二氯苯基)氨基]苯乙酰氯盐酸盐 | 1003579-49-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-[(2,6-二氯苯基)氨基]苯乙酰氯盐酸盐
• 英文名称: 2-[(2,6-dichlorophenyl)amino]benzeneacetyl chloride hydrochloride
• 英文别名: 2-[2-(2,6-Dichloroanilino)phenyl]acetyl chloride;hydrochloride；2-[2-(2,6-dichloroanilino)phenyl]acetyl chloride;hydrochloride
• CAS: 1003579-49-4
• 化学式: C₁₄H₁₀Cl₃NO*ClH
• 分子量: 351.059
• InChiKey: BJLFLCXNVFVWPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.47
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  29.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[(2,6-二氯苯基)氨基]苯乙酰氯盐酸盐 、 溶剂黄146 在 三乙胺 作用下， 以 氯仿 为溶剂， 反应 3.0h， 以85.6%的产率得到diethylaminoethyl 2-[(2,6-dichlorophenyl)amino]benzeneacetate acetate
  参考文献：
  名称：

  WO2008/12602

  摘要：

  公开号：

文献信息

• HIGH PENETRATION COMPOSITIONS AND USES THEREOF
  申请人：Yu Chongxi

  公开号：US20090238763A1

  公开（公告）日：2009-09-24

  The present invention relates to compositions and uses of novel high penetration compositions or high penetration prodrugs (HPP), in particular HPPs for non-steroidal anti-inflammatory agents (NSAIAs), 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性组合物或高渗透性前药（HPP）的组成和用途，特别是用于非甾体抗炎药（NSAIAs）的HPP，其能够高效地穿过生物屏障。这里的HPP能够在穿过生物屏障后转化为父活性药物或药物代谢物，从而可以治疗与父药物或代谢物相关的疾病。此外，由于能够穿过生物屏障，这里的HPP能够到达父药物可能无法进入或无法在目标区域产生足够浓度的区域，从而提供新的治疗方法。这里的HPP可以通过各种给药途径给予受试者。例如，由于其穿透生物屏障的能力，HPP可以在局部给药到疾病作用部位并以高浓度存在，从而避免系统性给药的需要。另一个例子是，这里的HPP可以被系统性地给药到生物体内，并以更快的速率进入循环系统。
• Positively charged water-soluble prodrugs of diclofenac with very fast skin penetration rate
  申请人：Techfields Biochem Co. Ltd

  公开号：EP2756843A2

  公开（公告）日：2014-07-23

  The novel positively charged pro-drugs of diclofenac in the general formula (1), with X = O or S, were designed and synthesized. The compounds of the general formula (1) can be prepared from functional derivatives of diclofenac by reaction with suitable alcohols, thiols, or amines. The positively charged amino groups of these pro-drugs not only largely increase the solubility of the drugs in water, but also bond to the negative charge on the phosphate head group of membranes and push the pro-drug into the cytosol. Experimental results suggest that the pro-drug diethylaminoethyl 2[(2,6-dichlorophenyl)amino]benzene acetate.AcOH diffuses through human skin 250 times faster than 2[(2,6-dichlorophenyl)amino]benzene acetic acid (diclofenac) and ethyl 2[(2,6-dichlorophenyl)amino]benzene acetate. In plasma, more than 90% of these pro-drugs can change back to the drug in a few minutes. The prodrugs can be used medicinally in treating any diclofenac-treatable conditions in humans or animals and be administered not only orally, but also transdermally for any kind of medical treatments and avoid most of the side effects of diclofenac, most notably GI disturbances such as dyspepsia, gastroduodenal bleeding, gastric ulcerations, and gastritis. Controlled transdermal administration systems of the prodrug enables diclofenac to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of diclofenac.

  我们设计并合成了通式（1）中带正电荷的新型双氯芬酸原药，其中 X = O 或 S。通式（1）的化合物可由双氯芬酸的功能性衍生物通过与适当的醇、硫醇或胺反应制备而成。这些原药带正电荷的氨基不仅能大大增加药物在水中的溶解度，还能与膜上磷酸头基的负电荷结合，将原药推入细胞质中。实验结果表明，原药 2[(2,6-二氯苯基)氨基]苯乙酸二乙氨基乙酯.AcOH 在人体皮肤中的扩散速度比 2[(2,6-二氯苯基)氨基]苯乙酸（双氯芬酸）和 2[(2,6-二氯苯基)氨基]苯乙酸乙酯快 250 倍。在血浆中，90% 以上的原药可在几分钟内变回药物。这些原药可用于治疗人类或动物的任何双氯芬酸可治疗的疾病，不仅可以口服，还可以透皮给药，用于任何类型的医疗，并可避免双氯芬酸的大部分副作用，尤其是消化道紊乱，如消化不良、胃十二指肠出血、胃溃疡和胃炎。原药的可控透皮给药系统可使双氯芬酸不断达到最佳治疗血药浓度，从而提高疗效并减少双氯芬酸的副作用。
• POSITIVELY CHARGED WATER-SOLUBLE PRODRUGS OF DICLOFENAC WITH VERY FAST SKIN PENETRATION RATE
  申请人：Techfields Biochem Co. Ltd

  公开号：EP2046727B1

  公开（公告）日：2014-03-12
• US9872846B2
  申请人：——

  公开号：US9872846B2

  公开（公告）日：2018-01-23
• [EN] POSITIVELY CHARGED WATER-SOLUBLE PRODRUGS OF DICLOFENAC WITH VERY FAST SKIN PENETRATION RATE<br/>[FR] PROMÉDICAMENTS HYDROSOLUBLES À CHARGE POSITIVE DU DICLOFÉNAC PRÉSENTANT UNE VITESSE DE PÉNÉTRATION CUTANÉE TRÈS RAPIDE
  申请人：TECHFIELDS BIOCHEM CO LTD

  公开号：WO2008012602A1

  公开（公告）日：2008-01-31

  [EN] The novel positively charged pro-drugs of diclofenac 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 functional derivatives of diclofenac (for example acid halides or mixed anhydrides), by reaction with suitable alcohols, thiols, or amines. 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 push the pro-drug into the cytosol. The experiment results suggest that the pro-drug, diethylaminoethyl 2[(2,6-dichlorophenyl)amino]benzene acetate.AcOH diffuses through human skin ~250 times faster than do 2[(2,6-dichlorophenyl)amino]benzene acetic acid (diclofenac) and ethyl 2[(2,6-dichlorophenyl)amino]benzene acetate. In plasma, more than 90% of these pro-drugs can change back to the drug in a few minutes. The prodrugs can be used medicinally in treating any diclofenac-treatable conditions in humans or animals and be administered not only orally, but also transdermally for any kind of medical treatments and avoid most of the side effects of diclofenac, most notably GI disturbances such as dyspepsia, gastroduodenal bleeding, gastric ulcerations, and gastritis. Controlled transdermal administration systems of the prodrug enables the diclofenac to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of diclofenac.
  [FR] L'invention porte sur la conception et la synthèse de nouveaux promédicaments à charge positive du diclofénac de formule générale (1) "Structure 1". Les composés de formule générale (1) "Structure 1" indiqués ci-dessus peuvent être préparés à partir de dérivés fonctionnels du diclofénac (par exemple d'hydracides ou d'anhydrides mélangés) par mise en réaction avec des alcools, des thiols ou des amines appropriés. Les groupes amino à charge positive de ces promédicaments peuvent non seulement augmenter largement la solubilité de ces médicaments dans l'eau, mais aussi se lier à la charge négative sur le groupe de tête phosphatique de membranes et pousser le promédicament vers le cytosol. Les résultats de l'expérience suggèrent que ce promédicament, l'acétate de diéthylaminoéthyl 2[(2,6-dichlorophényl)amino]benzène AcOH, se diffuse à travers la peau humaine ~250 fois plus rapidement que l'acide acétique de 2[(2,6-dichlorophényl)amino]benzène (diclofénac) lui-même et l'acétate d'éthyle 2[(2,6-dichlorophényl)amino]benzène. 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 au diclofénac chez l'homme ou chez l'animal et peuvent être administrés non seulement par voie orale, mais aussi par voie transdermique pour tout type de traitements médicaux. Ces promédicaments évitent également la plupart des effets secondaires du diclofénac, plus particulièrement les troubles gastro-intestinaux tels que la dyspepsie, le saignement gastroduodénal, les ulcérations gastriques et la gastrite. Des systèmes d'administration par voie transdermique contrôlée dudit promédicament permettent au diclofénac d'atteindre en permanence des concentrations sanguines thérapeutiques optimales pour une plus grande efficacité du diclofénac et moins d'effets secondaires.