(2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(12-(3-(adamantan-1-yl)ureido)dodecanamido)tetrahydro-2H-pyran-3,4,5-triyl triacetate | 931106-05-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(12-(3-(adamantan-1-yl)ureido)dodecanamido)tetrahydro-2H-pyran-3,4,5-triyl triacetate
• CAS: 931106-05-7
• 化学式: C₃₇H₅₉N₃O₁₁
• 分子量: 721.889
• InChiKey: KSMFUGFRRTWAGM-SAJZDAPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.35
• 重原子数：
  51.0
• 可旋转键数：
  19.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  184.66
• 氢给体数：
  3.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(12-(3-(adamantan-1-yl)ureido)dodecanamido)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 sodium methylate 作用下， 以 乙醇 为溶剂， 生成 N-(1'-oxo-1'-((2''R,3''S,4''R,5''S)-3'',4'',5''-trihydroxy-6''-(hydroxymethyl)tetrahydro-2H-pyran-2''-ylamino)decan-2'-yl)-12-(3-(1-adamantyl)ureido)dodecanoylamide
  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：

  异氰酸1-金刚烷酯 在 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 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(12-(3-(adamantan-1-yl)ureido)dodecanamido)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  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