2-{(2R,4aR,5S,6R,7aS)-5-[(4-chloro-3,5-dimethylphenoxy)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-3,5-dimethylphenoxy)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-3,5-dimethylphenoxy)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: C₂₁H₂₄ClNO₅S
• 分子量: 437.944
• InChiKey: DLFJVOCVUALUNF-TWPTVVAISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 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-3,5-dimethylphenoxy)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 HAVING EP2 AGONISTIC ACTIVITY
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：EP3327018A1

  公开（公告）日：2018-05-30

  Provided is an EP2 agonist having excellent safety. A compound represented by general formula (I) (wherein all symbols are as defined in the description), a salt or N-oxide of the compound, or a solvate or prodrug of the compound or the salt or N-oxide has an EP2 agonist activity and is highly safe, and is therefore useful as a medicine, particularly a therapeutic agent for diseases associated with EP2 receptors, such as 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 and cartilage injury.

  本文提供了一种安全性极佳的 EP2 激动剂。通式（I）代表的化合物 (其中所有符号如描述中所定义）代表的化合物、该化合物的盐或 N-氧化物、或该化合物或其盐或 N-氧化物的溶解物或原药具有 EP2 激动剂活性且安全性极高，因此可用作药物，特别是 EP2 受体相关疾病的治疗剂、如免疫性疾病、过敏性疾病、神经元死亡、痛经、早产、流产、秃头、眼部疾病、勃起功能障碍、关节炎、肺损伤、肺纤维化、肺气肿、支气管炎、慢性阻塞性肺病、骨病和软骨损伤。
• Compound having EP2 agonist activity
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US10385045B2

  公开（公告）日：2019-08-20

  Provided is an EP2 agonist having excellent safety. A compound represented by general formula (I) (wherein all symbols are as defined in the description), a salt or N-oxide of the compound, or a solvate or prodrug of the compound or the salt or N-oxide has an EP2 agonist activity and is highly safe, and is therefore useful as a medicine, particularly a therapeutic agent for diseases associated with EP2 receptors, such as 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 and cartilage injury.

  本文提供了一种安全性极佳的 EP2 激动剂。通式（I）代表的化合物 (其中所有符号如描述中所定义）代表的化合物、该化合物的盐或 N-氧化物、或该化合物或其盐或 N-氧化物的溶解物或原药具有 EP2 激动剂活性，安全性高，因此可用作药物，特别是 EP2 受体相关疾病的治疗剂、如免疫性疾病、过敏性疾病、神经元死亡、痛经、早产、流产、秃头、眼部疾病、勃起功能障碍、关节炎、肺损伤、肺纤维化、肺气肿、支气管炎、慢性阻塞性肺病、骨病和软骨损伤。
• 2-(OCTAHYDROCYCLOPENTA[B]PYRAN-2-YL)1,3-THIAZOLE-4-CARBOXYLIC ACID DERIVATIVES AND RELATED COMPOUNDS AS EP2 AGONISTS WITH INTRAOCULAR PRESSURE LOWERING ACTIVITY
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：EP3327018B1

  公开（公告）日：2020-11-25
• COMPOUND HAVING EP2 AGONIST ACTIVITY
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US20180215747A1

  公开（公告）日：2018-08-02

  Provided is an EP2 agonist having excellent safety. A compound represented by general formula (I) (wherein all symbols are as defined in the description), a salt or N-oxide of the compound, or a solvate or prodrug of the compound or the salt or N-oxide has an EP2 agonist activity and is highly safe, and is therefore useful as a medicine, particularly a therapeutic agent for diseases associated with EP2 receptors, such as 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 and cartilage injury.
• Structural optimization and structure–functional selectivity relationship studies of G protein-biased EP2 receptor agonists
  作者：Seiji Ogawa、Toshihide Watanabe、Kazumi Moriyuki、Yoshikazu Goto、Shinsaku Yamane、Akio Watanabe、Kazuma Tsuboi、Atsushi Kinoshita、Takuya Okada、Hiroyuki Takeda、Kousuke Tani、Toru Maruyama

  DOI：10.1016/j.bmcl.2016.03.110

  日期：2016.5

  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.