prostaglandin H2 1-ethanolamide 9,11-cycloendoperoxide | 398138-27-7

• 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: prostaglandin H2 1-ethanolamide 9,11-cycloendoperoxide
• 英文别名: prostaglandin H2 1-ethanolamide；(Z)-N-(2-hydroxyethyl)-7-[(1R,4S,5R,6R)-6-[(E,3S)-3-hydroxyoct-1-enyl]-2,3-dioxabicyclo[2.2.1]heptan-5-yl]hept-5-enamide
• CAS: 398138-27-7
• 化学式: C₂₂H₃₇NO₅
• 分子量: 395.539
• InChiKey: GOUQZQORWGWEFM-WLOFLUCMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  88
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  prostaglandin H2 1-ethanolamide 9,11-cycloendoperoxide 在 Proctacyclin Synthase 作用下， 生成 prostacyclin 1-ethanolamide
  参考文献：
  名称：

  9,11-cycloendoperoxide pro-drugs of prostaglandin analogues for treatment of ocular hypertension and glaucoma

  摘要：

  9,11-环内过氧化物衍生物是生物活性前列腺素类似物，特别是眼压降药物比马前列素、拉坦前列素、尤诺前列素、曲普前列素和前列腺素H2-乙醇胺或结构上密切相关的类似物的前体药物，在生理条件下水解，提供能够提供相应药物持续眼部和其他体内浓度的前列腺素类似物。本发明的化合物具有下面所示的公式，其中变量的含义在说明书中定义。

  公开号：

  US20040023954A1
• 作为产物：
  描述：

  大麻素 在 hCOX-2 作用下， 以 乙醇 为溶剂， 反应 0.03h， 以30%的产率得到prostaglandin H2 1-ethanolamide 9,11-cycloendoperoxide
  参考文献：
  名称：

  9,11-cycloendoperoxide pro-drugs of prostaglandin analogues for treatment of ocular hypertension and glaucoma

  摘要：

  9,11-环内过氧化物衍生物是生物活性前列腺素类似物，特别是眼压降药物比马前列素、拉坦前列素、尤诺前列素、曲普前列素和前列腺素H2-乙醇胺或结构上密切相关的类似物的前体药物，在生理条件下水解，提供能够提供相应药物持续眼部和其他体内浓度的前列腺素类似物。本发明的化合物具有下面所示的公式，其中变量的含义在说明书中定义。

  公开号：

  US20040023954A1

文献信息

• Molecular Characterization of a Novel Type of Prostamide/Prostaglandin F Synthase, Belonging to the Thioredoxin-like Superfamily
  作者：Hiroshi Moriuchi、Noriko Koda、Emiko Okuda-Ashitaka、Hiromi Daiyasu、Kensuke Ogasawara、Hiroyuki Toh、Seiji Ito、David F. Woodward、Kikuko Watanabe

  DOI：10.1074/jbc.m705638200

  日期：2008.1

  Prostaglandin F (PGF) ethanolamide (prostamide F) synthase, which catalyzed the reduction of prostamide H-2 to prostamide F-2 alpha,F-, was found in mouse and swine brain. The enzyme was purified from swine brain, and its amino acid sequence was defined. The mouse enzyme consisted of a 603-bp open reading frame coding for a 201-amino acid polypeptide with a molecular weight of 21,669. The amino acid sequence placed the enzyme in the thioredoxin-like superfamily with Cys(44) being the active site. The enzyme expressed in Escherichia coli as well as the native enzyme catalyzed not only the reduction of prostamide H-2 to prostamide F-2 alpha but also that of PGH(2) to PGF(2 alpha). The V-max and Km values for prostamide H-2 were about 0.25 mu mol/min center dot mg of protein and 7.6 mu M, respectively, and those for PGH(2) were about 0.69 mu mol/min center dot mg of protein and 6.9 mu M, respectively. Neither PGE(2) nor PGD(2) served as a substrate for this synthase. Based on these data, we named the enzyme prostamide/PGF synthase. Although the enzyme showed a broad specificity for reductants, reduced thioredoxin preferentially served as a reducing equivalent donor for this enzyme. Moreover, Northern and Western blot analyses in addition to the prostamide F synthase activity showed that the enzyme was mainly distributed in the brain and spinal cord, and the immunohistochemical study in the spinal cord showed that the enzyme was found mainly in the cytosol. These results suggest that prostamide/PGF synthase may play an important functional role in the central nervous system.
• Enzymatic formation of prostamide F2α from anandamide involves a newly identified intermediate metabolite, prostamide H2
  作者：Wu Yang、Jinsong Ni、David F. Woodward、Diane D-S. Tang-Liu、Kah-Hiing John Ling

  DOI：10.1194/jlr.m500374-jlr200

  日期：2005.12

  Prostaglandin F-2 alpha 1-ethanolamide (prostamideF(2 alpha)) is a potent ocular hypotensive agent in animals and represents a new class of fatty acid amide compounds. Accumulated evidence indicated that anandamide, an endogenous bioactive ligand for cannabinoid receptors, may serve as a common substrate to produce all prostamides, including prostamide F-2 alpha. After incubation of anandamide with cyclooxygenase 2 (COX-2), the reaction mixture was profiled by HPLC and an intermediate metabolite was discovered and characterized as a cyclic endoperoxide ethanolamide using HPLC-tandem mass spectrometry. Formation of prostamide F-2 alpha was also demonstrated when the intermediate metabolite was isolated and incubated with prostaglandin F synthase (PGF synthase). These results suggest that the biosynthesis of prostamide F-2 alpha proceeds in two consecutive steps: oxidation of anandamide to form an endoperoxide intermediate by COX-2, and reduction of the endoperoxide intermediate to form prostamide F-2 alpha by PGF synthase. This endoperoxide ethanolamide intermediate has been proposed as prostamide H-2.
• Prostamides (prostaglandin-ethanolamides) and their pharmacology
  作者：D F Woodward、Y Liang、A H-P Krauss

  DOI：10.1038/sj.bjp.0707434

  日期：2008.2

  The prostamides are part of a large and continually expanding series of pharmacologically unique neutral lipids. They are COX‐2 derived oxidation products of the endocannabinoid/endovanniloid anandamide. Prostamide pharmacology is unique and, as in the case of the endocannabinoids anandamide and 2‐arachidonylglycerol, bears little resemblance to that of the corresponding free acids. By virtue of its close relationship to the anti‐glaucoma drug bimatoprost, prostamide F2α has received the greatest research attention. Prostamide F2α and bimatoprost effects appear independent of prostanoid FP receptor activation, according to a litany of agonist studies. Studies involving freshly isolated and separate feline iridial smooth muscle cells revealed that bimatoprost and FP receptor agonists stimulated different cells, without exception. This suggests the existence of receptors that preferentially recognize prostamide F2α. The recent discovery of prostamide antagonists has provided further support for prostamide receptors as discrete entities. The prototypical prostamide antagonists, AGN 204396 and 7, blocked the effects of prostamide F2α and bimatoprost but not those of PGF2α and FP receptor agonists in the feline iris. Second generation more potent prostamide antagonists, such as AGN 211334, should allow the role of prostamides in health and disease to be elucidated. From the therapeutics standpoint, the prostamide F2α analogue bimatoprost is the most efficacious ocular hypotensive agent currently available for the treatment of glaucoma.British Journal of Pharmacology (2008) 153, 410–419; doi:10.1038/sj.bjp.0707434; published online 27 August 2007