16-(3-methoxymethyl)phenyl-ω-tetranor-5-thiaprostaglandin F₁ methyl ester 11,15-bis(tetrahydropyran-2-yl ether) | 256382-45-3

• 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: 16-(3-methoxymethyl)phenyl-ω-tetranor-5-thiaprostaglandin F₁ methyl ester 11,15-bis(tetrahydropyran-2-yl ether)
• 英文别名: (9α,11α,15α,13E)-9-hydroxy-11,15-bis(tetrahydropyran-2-yloxy)-16-(3-methoxymethylphenyl)-17,18,19,20-tetranor-5-thiaprost-13-enoic acid methyl ester；methyl 4-[2-[(1R,2R,3R,5S)-5-hydroxy-2-[(E,3S)-4-[3-(methoxymethyl)phenyl]-3-(oxan-2-yloxy)but-1-enyl]-3-(oxan-2-yloxy)cyclopentyl]ethylsulfanyl]butanoate
• CAS: 256382-45-3
• 化学式: C₃₄H₅₂O₈S
• 分子量: 620.848
• InChiKey: BPBIQRJOTCWUHX-HIYUPFPPSA-N

物化性质

• 沸点：
  715.5±60.0 °C(predicted)
• 密度：
  1.17±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  43
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  16-(3-methoxymethyl)phenyl-ω-tetranor-5-thiaprostaglandin F₁ methyl ester 11,15-bis(tetrahydropyran-2-yl ether) 在 盐酸 、 pyridine-SO3 complex 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二甲基亚砜 、 乙酸乙酯 、 乙腈 为溶剂， 反应 3.83h， 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 、 potassium carbonate 、 对甲苯磺酸 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 11.67h， 生成 16-(3-methoxymethyl)phenyl-ω-tetranor-5-thiaprostaglandin F₁ methyl ester 11,15-bis(tetrahydropyran-2-yl ether)
  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

• REMEDIES FOR DISEASES WITH BONE MASS LOSS HAVING EP4 AGONIST AS THE ACTIVE INGREDIENT
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1417975B1

  公开（公告）日：2011-03-02
• Design and synthesis of a selective EP4-receptor agonist. Part 3: 16-phenyl-5-thiaPGE1 and 9-β-halo derivatives with improved stability
  作者：T Maruyama

  DOI：10.1016/s0968-0896(02)00031-7

  日期：2002.6

  To identify a new selective EP4-agonist with improved chemical stability, further chemical modification of those reported previously was continued. We focused our attention on chemical modification of the alpha chain of 3,7-dithiaPGE(1), and selected 5-thiaPGE(1), as a new chemical lead, Introduction of an optimized omega to chain to the 5-thiaPG skeleton afforded in-methoxymethyl derivative 33a, which showed the most potent EP4-receptor agonist activity and good subtype-selectivity both in vitro and in vivo. 9beta-HaloPGF derivatives were also synthesized and biologically evaluated in an attempt to block self-degradation of the beta-hydroxyketone moiety. Among these series, 39a and 39b showed potent agonist activity and good subtype-selectivity. Structure-activity relationships (SARs) are also discussed. (C) 2002 Elsevier Science Ltd. All rights reserved.