2-[12-(3-adamantan-1-yl-ureido)dodecanoylamino]decanoic acid | 860623-14-9

• 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: 2-[12-(3-adamantan-1-yl-ureido)dodecanoylamino]decanoic acid
• 英文别名: 2-[12-(3-Adamantan-1-yl-ureido)-dodecanoylamino]-decanoic acid；2-[12-(1-adamantylcarbamoylamino)dodecanoylamino]decanoic acid
• CAS: 860623-14-9
• 化学式: C₃₃H₅₉N₃O₄
• 分子量: 561.849
• InChiKey: GCBZVCHTUVZTEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  40
• 可旋转键数：
  22
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[12-(3-adamantan-1-yl-ureido)dodecanoylamino]decanoic acid 在 sodium methylate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 12-(3-(1-adamantyl)ureido)dodecanoic acid [1-(2,3,4-trihydroxy-5-hydroxymethylcyclohexylcarbamoyl)nonyl]amide
  参考文献：
  名称：

  Design of bioavailable derivatives of 12-(3-adamantan-1-yl-ureido)dodecanoic acid, a potent inhibitor of the soluble epoxide hydrolase

  摘要：

  The soluble epoxide hydrolase (sEH) plays an important role in the metabolism of endogenous chemical mediators involved in blood pressure regulation and vascular inflammation. 12-(3-Adamantan-1-yl-ureido)-dodecanoic acid (AUDA, 1) is a very active inhibitor of sEH both in vitro and in vivo. However, its relatively high melting point and limited solubility in either water or oil-based solvents leads to difficulties in formulating the compound and often results in poor in vivo availability. We investigated the effect of derivatization of the acid functional group of inhibitor I on the inhibition potencies, physical properties, and pharmacokinetic properties. For human sEH, similar inhibition potency was obtained when the acid of compound I was modified to esters (2-15). The resulting compounds exhibited improved physical properties (23-66 degrees C lower melting point and 5-fold better solubility in oil). Pharmacokinetic studies showed that the esters possess improved oral bioavailability in mice. On the other hand, amide derivatives of AUDA I did not show significant improvement in inhibition potencies or physical properties (higher melting points and lower solubility). The esterification of 1 results in compounds that are easier to formulate in animal food and in triglycerides for gavage and other routes of administration, making it easier to study the biological effects of sEH inhibition in vivo. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.057
• 作为产物：
  描述：

  12-氨基十二酸 在 lithium hydroxide 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 2-[12-(3-adamantan-1-yl-ureido)dodecanoylamino]decanoic acid
  参考文献：
  名称：

  Design of bioavailable derivatives of 12-(3-adamantan-1-yl-ureido)dodecanoic acid, a potent inhibitor of the soluble epoxide hydrolase

  摘要：

  The soluble epoxide hydrolase (sEH) plays an important role in the metabolism of endogenous chemical mediators involved in blood pressure regulation and vascular inflammation. 12-(3-Adamantan-1-yl-ureido)-dodecanoic acid (AUDA, 1) is a very active inhibitor of sEH both in vitro and in vivo. However, its relatively high melting point and limited solubility in either water or oil-based solvents leads to difficulties in formulating the compound and often results in poor in vivo availability. We investigated the effect of derivatization of the acid functional group of inhibitor I on the inhibition potencies, physical properties, and pharmacokinetic properties. For human sEH, similar inhibition potency was obtained when the acid of compound I was modified to esters (2-15). The resulting compounds exhibited improved physical properties (23-66 degrees C lower melting point and 5-fold better solubility in oil). Pharmacokinetic studies showed that the esters possess improved oral bioavailability in mice. On the other hand, amide derivatives of AUDA I did not show significant improvement in inhibition potencies or physical properties (higher melting points and lower solubility). The esterification of 1 results in compounds that are easier to formulate in animal food and in triglycerides for gavage and other routes of administration, making it easier to study the biological effects of sEH inhibition in vivo. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.057

文献信息

• Inhibitors for the Soluble Epoxide Hydrolase
  申请人：HAMMOCK BRUCE D.

  公开号：US20110021448A1

  公开（公告）日：2011-01-27

  Inhibitors of the soluble epoxide hydrolase (sEH) are provided that incorporate multiple pharmacophores and are useful in the treatment of diseases.

  提供了可用于治疗疾病的可溶性环氧酶（sEH）抑制剂，其中包含多个药效团。
• [EN] IMPROVED INHIBITORS FOR THE SOLUBLE EPOXIDE HYDROLASE<br/>[FR] INHIBITEURS AMELIORES DE L'EPOXYDE HYDROLASE SOLUBLE
  申请人：UNIV CALIFORNIA

  公开号：WO2006045119A3

  公开（公告）日：2007-02-08
• US7662910B2
  申请人：——

  公开号：US7662910B2

  公开（公告）日：2010-02-16
• US8476043B2
  申请人：——

  公开号：US8476043B2

  公开（公告）日：2013-07-02
• Design of bioavailable derivatives of 12-(3-adamantan-1-yl-ureido)dodecanoic acid, a potent inhibitor of the soluble epoxide hydrolase
  作者：In-Hae Kim、Kosuke Nishi、Hsing-Ju Tsai、Tanya Bradford、Yasuko Koda、Takaho Watanabe、Christophe Morisseau、Joanne Blanchfield、Istvan Toth、Bruce D. Hammock

  DOI：10.1016/j.bmc.2006.09.057

  日期：2007.1.1

  The soluble epoxide hydrolase (sEH) plays an important role in the metabolism of endogenous chemical mediators involved in blood pressure regulation and vascular inflammation. 12-(3-Adamantan-1-yl-ureido)-dodecanoic acid (AUDA, 1) is a very active inhibitor of sEH both in vitro and in vivo. However, its relatively high melting point and limited solubility in either water or oil-based solvents leads to difficulties in formulating the compound and often results in poor in vivo availability. We investigated the effect of derivatization of the acid functional group of inhibitor I on the inhibition potencies, physical properties, and pharmacokinetic properties. For human sEH, similar inhibition potency was obtained when the acid of compound I was modified to esters (2-15). The resulting compounds exhibited improved physical properties (23-66 degrees C lower melting point and 5-fold better solubility in oil). Pharmacokinetic studies showed that the esters possess improved oral bioavailability in mice. On the other hand, amide derivatives of AUDA I did not show significant improvement in inhibition potencies or physical properties (higher melting points and lower solubility). The esterification of 1 results in compounds that are easier to formulate in animal food and in triglycerides for gavage and other routes of administration, making it easier to study the biological effects of sEH inhibition in vivo. (c) 2006 Elsevier Ltd. All rights reserved.