6-{(1E)(3S)-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl}-7-(2H-3,4,5,6-tetrahydropyran-2-yloxy)(5S,7S,1R,6R)-2-oxabicyclo[3.3.0]octan-3-one | 256382-41-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-{(1E)(3S)-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl}-7-(2H-3,4,5,6-tetrahydropyran-2-yloxy)(5S,7S,1R,6R)-2-oxabicyclo[3.3.0]octan-3-one
• 英文别名: (1S,5R,6R,7R)-3-oxo-6-(4-(3-methoxymethylphenyl)-3S-hydroxy-1-butenyl)-7-(2-tetrahydropyranyloxy)-2-oxabicyclo[3.3.0]octane；(3aR,4R,5R,6aS)-4-[(E,3S)-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl]-5-(oxan-2-yloxy)-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one
• CAS: 256382-41-9
• 化学式: C₂₄H₃₂O₆
• 分子量: 416.514
• InChiKey: IBIATRNNEKALQM-NWVDTULXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-{(1E)(3S)-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl}-7-(2H-3,4,5,6-tetrahydropyran-2-yloxy)(5S,7S,1R,6R)-2-oxabicyclo[3.3.0]octan-3-one 在 盐酸 、 lithium aluminium tetrahydride 、 pyridine-SO3 complex 、 potassium carbonate 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 12.0h， 生成 甲基4-({2-[(1R,2R,3S)-3-羟基-2-{(1E)-3-羟基-4-[3-(甲氧基甲基)苯基]-1-丁烯-1-基}-5-氧代环戊基]乙基}硫基)丁酸酯
  参考文献：
  名称：

  Design and synthesis of a selective EP4-receptor agonist. Part 4: practical synthesis and biological evaluation of a novel highly selective EP4-receptor agonist

  摘要：

  A practical method of synthesizing it highly selective EP4-receptor agonist 1 using Corey lactone 2 as a key intermediate was developed. Selective methanesulfonylation of the primary alcohol of the diol 8 under the newly devised conditions followed by the protection of the remaining secondary alcohol are key reactions in this new method. Further biological evaluation of 1a-b is also reported. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00085-8
• 作为产物：
  描述：

  科立内酯 在 lithium aluminium tetrahydride 、 pyridine-SO3 complex 、 S-1,1'-联-2-萘酚 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 3.5h， 生成 6-{(1E)(3S)-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl}-7-(2H-3,4,5,6-tetrahydropyran-2-yloxy)(5S,7S,1R,6R)-2-oxabicyclo[3.3.0]octan-3-one
  参考文献：
  名称：

  Design and synthesis of a selective EP4-receptor agonist. Part 4: practical synthesis and biological evaluation of a novel highly selective EP4-receptor agonist

  摘要：

  A practical method of synthesizing it highly selective EP4-receptor agonist 1 using Corey lactone 2 as a key intermediate was developed. Selective methanesulfonylation of the primary alcohol of the diol 8 under the newly devised conditions followed by the protection of the remaining secondary alcohol are key reactions in this new method. Further biological evaluation of 1a-b is also reported. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00085-8

文献信息

• 5-thia-&ohgr;-substituted phenyl-prostaglandin E derivatives, process for producing the same and drugs containing the same as the active ingredient
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：US06462081B1

  公开（公告）日：2002-10-08

  The present invention relates to 5-thia-&ohgr;-substituted phenylprostaglandin E derivatives of the formula (I) (wherein, all the symbols are as defined in the specification), process for producing them and pharmaceutical compositions comprising them as active ingredient. The compounds of the formula (I) can bind to PGE2 receptors (especially, subtype EP4) strongly, so they are expected to be useful for prevention and/or treatment of immunological diseases (autoimmune diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis, Sjoegren's syndrome, chronic rheumarthrosis and systemic lupus erythematosus etc., and rejection after organ transplantation etc.), asthma, abnormal bone formation, neuronal cell death, lung failure, liver damage, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardiac ischemia, systemic inflammatory response syndrome, ambustion pain, sepsis, hemophagous syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, and shock etc. Further, it is thought that EP4 subtype receptor relates to sleeping disorder and blood platelet aggregation, so the compounds of the present invention are expected to be useful for the prevention and/or treatment of such diseases.

  本发明涉及公式(I)的5-硫代-ω-取代苯基前列腺素E衍生物（其中，所有符号如规范中所定义），生产它们的方法以及包含它们作为活性成分的药物组合物。公式(I)的化合物可以强烈结合到PGE2受体（尤其是EP4亚型），因此预计它们对预防和/或治疗免疫性疾病（自身免疫疾病，如肌萎缩性侧索硬化（ALS），多发性硬化症，Sjögren综合症，慢性风湿性关节炎和系统性红斑狼疮等，器官移植后的排斥等），哮喘，异常骨形成，神经细胞死亡，肺功能衰竭，肝损伤，急性肝炎，肾炎，肾功能不全，高血压，心肌缺血，全身性炎症反应综合征，烧伤疼痛，败血症，血吞噬综合征，巨噬细胞活化综合征，Still氏病，川崎病，烧伤，全身性肉芽肿，溃疡性结肠炎，克罗恩病，透析时的高细胞因子血症，多器官功能衰竭和休克等方面有用。此外，据认为EP4亚型受体与睡眠障碍和血小板聚集有关，因此本发明的化合物预计对预防和/或治疗此类疾病有用。
• 5-THIA-OMEGA-SUBSTITUTED PHENYL-PROSTAGLANDIN E DERIVATIVES, PROCESS FOR PRODUCING THE SAME AND DRUGS CONTAINING THE SAME AS THE ACTIVE INGREDIENT
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1097922A1

  公开（公告）日：2001-05-09

  5-Thia-ω-substituted phenyl-prostaglandin E derivatives represented by general formula (I) wherein each symbol is as defined in the specification. Because of being capable of bonding strongly to PEG2receptors (in particular, the subtype EP4), the compounds represented by general formula (I) are expected as useful in preventing and/or treating immunologic diseases, asthma, bone dysplasia, nerve cell death, lung failure, hepatopathy, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardial ischemia, systemic inflammatory syndrome, ambustion pain, sepsis, hemophagous syndrome, macrophage activation syndrome, Still disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, shock, etc. Moreover, these compounds participate in sleep disorders and platelet aggregation and, therefore, are expected as useful in preventing/treating these diseases.

  通式（I）代表的 5-噻-ω-取代苯基-前列腺素 E 衍生物，其中各符号如说明书中所定义。肾功能不全、高血压、心肌缺血、全身炎症综合征、灸痛、败血症、嗜血综合征、巨噬细胞活化综合征、斯蒂尔病、川崎病、烧伤、全身肉芽肿病、溃疡性结肠炎、克罗恩病、透析时的高细胞血症、多器官衰竭、休克等。此外，这些化合物还参与睡眠障碍和血小板聚集，因此有望用于预防/治疗这些疾病。
• US6462081B1
  申请人：——

  公开号：US6462081B1

  公开（公告）日：2002-10-08
• Design and synthesis of a selective EP4-receptor agonist. Part 4: practical synthesis and biological evaluation of a novel highly selective EP4-receptor agonist
  作者：Toru Maruyama、Shin-Itsu Kuwabe、Yasufumi Kawanaka、Tai Shiraishi、Yoshiyuki Shinagawa、Kiyoto Sakata、Akiteru Seki、Yoko Kishida、Hideyuki Yoshida、Takayuki Maruyama、Shuichi Ohuchida、Hisao Nakai、Shinsuke Hashimoto、Masanori Kawamura、Kigen Kondo、Masaaki Toda

  DOI：10.1016/s0968-0896(02)00085-8

  日期：2002.7

  A practical method of synthesizing it highly selective EP4-receptor agonist 1 using Corey lactone 2 as a key intermediate was developed. Selective methanesulfonylation of the primary alcohol of the diol 8 under the newly devised conditions followed by the protection of the remaining secondary alcohol are key reactions in this new method. Further biological evaluation of 1a-b is also reported. (C) 2002 Elsevier Science Ltd. All rights reserved.