2-{(2R,4aR,5S,6R,7aS)-5-[(4-chloro-3-methylphenoxy)methyl]-6-hydroxyoctahydrocyclopenta[b]pyran-2-yl}-1,3-thiazole-4-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-{(2R,4aR,5S,6R,7aS)-5-[(4-chloro-3-methylphenoxy)methyl]-6-hydroxyoctahydrocyclopenta[b]pyran-2-yl}-1,3-thiazole-4-carboxylic acid
• 英文别名: 2-[(2R,4aR,5S,6R,7aS)-5-[(4-chloro-3-methylphenoxy)methyl]-6-hydroxy-2,3,4,4a,5,6,7,7a-octahydrocyclopenta[b]pyran-2-yl]-1,3-thiazole-4-carboxylic acid
• 化学式: C₂₀H₂₂ClNO₅S
• 分子量: 423.917
• InChiKey: GZTLLBIEEIZFFD-BSPHMWTBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  在 水 、 sodium hydroxide 作用下， 以 甲醇 、 乙二醇二甲醚 为溶剂， 生成 2-{(2R,4aR,5S,6R,7aS)-5-[(4-chloro-3-methylphenoxy)methyl]-6-hydroxyoctahydrocyclopenta[b]pyran-2-yl}-1,3-thiazole-4-carboxylic acid
  参考文献：
  名称：

  Structural optimization and structure–functional selectivity relationship studies of G protein-biased EP2 receptor agonists

  摘要：

  The modification of the novel G protein-biased EP2 agonist 1 has been investigated to improve its G protein activity and develop a better understanding of its structure-functional selectivity relationship (SFSR). The optimization of the substituents on the phenyl ring of 1, followed by the inversion of the hydroxyl group on the cyclopentane moiety led to compound 9, which showed a 100-fold increase in its G protein activity compared with 1 without any increase in beta-arrestin recruitment. Furthermore, SFSR studies revealed that the combination of meta and para substituents on the phenyl moiety was crucial to the functional selectivity. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.03.110

文献信息

• COMPOUND EXHIBITING SELECTIVE EP2 AGONIST ACTIVITY
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：EP3112362B1

  公开（公告）日：2018-09-26
• COMPOUND HAVING SELECTIVE EP2 AGONIST ACTIVITY
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US20170015657A1

  公开（公告）日：2017-01-19

  A compound represented by general formula (I) wherein all symbols are as defined in the specification, a salt or N-oxide of the compound, or a solvate or prodrug of the compound or the salt or N-oxide has a selective EP2 agonist activity and is highly safe, and is therefore useful as a drug, especially as a therapeutic agent for EP2 receptor-related diseases including immune diseases, allergic diseases, neuronal death, dysmenorrhea, premature birth, miscarriage, baldness, ocular diseases, erectile dysfunction, arthritis, lung injury, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, bone diseases, cartilage injury and others.
• US9890146B2
  申请人：——

  公开号：US9890146B2

  公开（公告）日：2018-02-13
• [EN] COMPOUND EXHIBITING SELECTIVE EP2 AGONIST ACTIVITY<br/>[FR] COMPOSÉ PRÉSENTANT UNE ACTIVITÉ SÉLECTIVE D'AGONISTE EP2<br/>[JA] 選択的ＥＰ２アゴニスト活性を有する化合物
  申请人：ONO PHARMACEUTICAL CO

  公开号：WO2015129782A1

  公开（公告）日：2015-09-03

  　安全性に優れた選択的ＥＰ２アゴニストを提供する。　一般式（Ｉ）： （式中、全ての記号は明細書中に示す通り。） で示される化合物、その塩、そのＮ－オキシド体、それらの溶媒和物、またはそれらのプロドラッグは、選択的ＥＰ２アゴニスト活性を有し、また安全性も高いため、医薬品、とりわけＥＰ２受容体に関連した疾患、例えば、免疫疾患、アレルギー性疾患、神経細胞死、月経困難症、早産、流産、禿頭症、眼疾患、勃起不全、関節炎、肺傷害、肺線維症、肺気腫、気管支炎、慢性閉塞性呼吸器疾患、骨疾患、軟骨損傷などの治療剤として有用である。