ethyl 4-cyclohexyl-3-hydroxy-3-methylbutanoate

• 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: ethyl 4-cyclohexyl-3-hydroxy-3-methylbutanoate
• 化学式: C₁₃H₂₄O₃
• 分子量: 228.332
• InChiKey: KVKZIVHFMZTTHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4-cyclohexyl-3-hydroxy-3-methylbutanoate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.58h， 生成 4-cyclohexyl-3-methyl-1,3-butanediol
  参考文献：
  名称：

  Synthesis and evaluation of a potent, well-balanced EP 2 /EP 3 dual agonist

  摘要：

  A highly potent and well-balanced dual agonist for the EP2 and EP3 receptors is described. Optimization of the lead compound was accomplished in consideration of the relative agonist activity against each EP subtype receptor and the pharmacokinetic profile. As the result, 2-[(2-{(1R,2R)-2-[(1E,4S)-5-cyclopentyl-4-hydroxy-4-methyl-1-penten-1-yl]-5-oxocyclopentyl}eth-yl)thio]-1,3-thiazole-4-carboxylic acid (10) showed excellent potency (human EC50 EP2 = 1.1 nM, EP3 = 1.0 nM) with acceptable selectivity over the EP1 and EP4 subtypes (> 2000-fold). Further fine-tuning of compound 10 led to identification of ONO-8055 as a clinical candidate. ONO-8055 was effective at an extremely low dose (0.01 mg/kg, po, bid) in rats, and dose-dependently improved voiding dysfunction in a monkey model of underactive bladder (UAB). ONO-8055 is expected to be a novel and highly promising drug for UAB. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.11.035
• 作为产物：
  描述：

  环己基丙酮 、 溴乙酸乙酯 在 碘 、 锌 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 ethyl 4-cyclohexyl-3-hydroxy-3-methylbutanoate
  参考文献：
  名称：

  Synthesis and evaluation of a potent, well-balanced EP 2 /EP 3 dual agonist

  摘要：

  A highly potent and well-balanced dual agonist for the EP2 and EP3 receptors is described. Optimization of the lead compound was accomplished in consideration of the relative agonist activity against each EP subtype receptor and the pharmacokinetic profile. As the result, 2-[(2-{(1R,2R)-2-[(1E,4S)-5-cyclopentyl-4-hydroxy-4-methyl-1-penten-1-yl]-5-oxocyclopentyl}eth-yl)thio]-1,3-thiazole-4-carboxylic acid (10) showed excellent potency (human EC50 EP2 = 1.1 nM, EP3 = 1.0 nM) with acceptable selectivity over the EP1 and EP4 subtypes (> 2000-fold). Further fine-tuning of compound 10 led to identification of ONO-8055 as a clinical candidate. ONO-8055 was effective at an extremely low dose (0.01 mg/kg, po, bid) in rats, and dose-dependently improved voiding dysfunction in a monkey model of underactive bladder (UAB). ONO-8055 is expected to be a novel and highly promising drug for UAB. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.11.035

文献信息

• AGENT FOR REGENERATION AND/OR PROTECTION OF NERVES
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1886693A1

  公开（公告）日：2008-02-13

  An EP2 agonist which may have an EP3 agonistic effect has an effect of regenerating and/or protecting nerves, and is therefore useful as a therapeutic agent for a disease of the peripheral nervous system, such as a lower or upper motor neuron disease, a nerve root disease, plexopathy, thoracic outlet compression syndrome, peripheral neuropathy, neurofibromatosis and neuromuscular transmission disease. An EP2 agonist which has an EP3 agonistic effect is a safe and effective agent for the regeneration and/or protection of nerves which has little influence on the circulatory system.

  可能具有 EP3 激动效应的 EP2 激动剂具有再生和/或保护神经的作用，因此可用作外周神经系统疾病的治疗剂，例如下运动神经元或上运动神经元疾病、神经根疾病、神经丛病、胸廓出口压迫综合征、外周神经病、神经纤维瘤病和神经肌肉传导疾病。具有 EP3 激动效应的 EP2 激动剂是一种安全有效的神经再生和/或保护剂，对循环系统的影响很小。
• Agent for regeneration and/or protection of nerves
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：EP2308510A1

  公开（公告）日：2011-04-13

  An EP2 agonist which may have an EP3 agonistic effect has an effect of regenerating and/or protecting nerves, and is therefore useful as a therapeutic agent for a disease of the peripheral nervous system, such as a lower or upper motor neuron disease, a nerve root disease, plexopathy, thoracic outlet compression syndrome, peripheral neuropathy, neurofibromatosis and neuromuscular transmission disease. An EP2 agonist which has an EP3 agonistic effect is a safe and effective agent for the regeneration and/or protection of nerves which has little influence on the circulatory system.

  可能具有 EP3 激动效应的 EP2 激动剂具有再生和/或保护神经的作用，因此可用作外周神经系统疾病的治疗剂，例如下运动神经元或上运动神经元疾病、神经根疾病、神经丛病、胸廓出口压迫综合征、外周神经病、神经纤维瘤病和神经肌肉传导疾病。具有 EP3 激动效应的 EP2 激动剂是一种安全有效的神经再生和/或保护剂，对循环系统的影响很小。
• EP1886693
  申请人：——

  公开号：——

  公开（公告）日：——
• EP2308510B1
  申请人：——

  公开号：EP2308510B1

  公开（公告）日：2016-03-16
• US7863263B2
  申请人：——

  公开号：US7863263B2

  公开（公告）日：2011-01-04