ethyl 2-({2-[(1R,2S,5S)-2-(acetyloxy)-5-formylcyclopentyl]ethyl}thio)-1,3-thiazole-4-carboxylate | 854000-06-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 2-({2-[(1R,2S,5S)-2-(acetyloxy)-5-formylcyclopentyl]ethyl}thio)-1,3-thiazole-4-carboxylate
• 英文别名: ethyl 2-[2-[(1R,2S,5S)-2-acetyloxy-5-formylcyclopentyl]ethylsulfanyl]-1,3-thiazole-4-carboxylate
• CAS: 854000-06-9
• 化学式: C₁₆H₂₁NO₅S₂
• 分子量: 371.478
• InChiKey: RCZYRHLEPSECKN-BZPMIXESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  136
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 2-({2-[(1R,2S,5S)-2-(acetyloxy)-5-formylcyclopentyl]ethyl}thio)-1,3-thiazole-4-carboxylate 在 吡啶 、 4-二甲氨基吡啶 、 2,4,6-三氯苯甲酰氯 、 水 、 双(三甲基硅烷基)氨基钾 、 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 1.25h， 生成 methyl 2-[(2-{(1R,2S,5R)-2-hydroxy-5-[(1E,4S)-7,8,8-trifluoro-4-hydroxy-4-methyl-1,7-octadien-1-yl]cyclopentyl}ethyl)thio]-1,3-thiazole-4-carboxylate
  参考文献：
  名称：

  COMPOUND HAVING DETRUSOR MUSCLE-CONTRACTING ACTIVITY AND URETHRAL SPHINCTER MUSCLE-RELAXING ACTIVITY

  摘要：

  由式(I)所代表的化合物，其中所有符号的定义与说明书中相同，其盐、溶剂合物、前药、任意比例的对映异构体混合物或环糊精包合物具有收缩膀胱去甲肌活性和放松尿道括约肌活性，它们可以改善膀胱收缩功能障碍和/或尿道松弛功能障碍，例如，对于无力膀胱非常有效。此外，本发明的化合物对泌尿系统、循环系统和消化系统的副作用风险很小，并表现出优异的药代动力学，如口服吸收等。因此，本发明的化合物在预防、治疗和/或改善无力膀胱方面具有优越的作用。

  公开号：

  US20120088805A1
• 作为产物：
  描述：

  ethyl 2-({2-[(1R,2S,5S)-2-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-hydroxycyclopentyl]ethyl}thio)-1,3-thiazole-4-carboxylate 在 吡啶 、 4-二甲氨基吡啶 、 四丁基氟化铵 、 三氧化硫吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 4.0h， 生成 ethyl 2-({2-[(1R,2S,5S)-2-(acetyloxy)-5-formylcyclopentyl]ethyl}thio)-1,3-thiazole-4-carboxylate
  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

• Blood flow promoters for cauda equina tissues
  申请人：Ohmoto Kazuyuki

  公开号：US20070129327A1

  公开（公告）日：2007-06-07

  It is intended to provide highly safe and efficacious blood flow promoters for cauda equina tissues. Among prostaglandin-like compounds having a weak hypotensive effect, compounds having an effect of promoting the blood flow in cauda equina tissues (excluding limaprost) are useful as highly safe blood flow promoters for cauda equina tissues and, therefore, are efficacious in preventing and/or treating lumbar pain, lower limb pain, lower limb palsy, intermittent claudication, vesicorectal failure, hypogonadism, etc. caused by cauda equina injuries.

  旨在为马尾神经组织提供高度安全和有效的血流促进剂。在具有弱降压作用的前列腺素类似化合物中，具有促进马尾神经组织血流的作用的化合物（不包括利马前列素）作为高度安全的马尾神经组织血流促进剂是有用的，并且在预防和/或治疗由马尾神经损伤引起的腰痛、下肢疼痛、下肢麻痹、间歇性跛行、膀胱直肠功能障碍、性腺功能减退等方面具有疗效。
• Compound having detrusor muscle-contracting activity and urethral sphincter muscle-relaxing activity
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：US08686160B2

  公开（公告）日：2014-04-01

  Since a compound represented by formula (I) wherein all of the symbols are the same as defined in the specification, a salt thereof, a solvate thereof, a prodrug thereof, a mixture with a diastereomer thereof in an arbitrary ratio, or a cyclodextrin clathrate thereof have a contracting activity of bladder detrusor and a relaxing activity of urethral sphincter, they can ameliorate bladder contraction dysfunction and/or urethral relaxation dysfunction, and for example, are effective for underactive bladder. Additionally, the compound of the present invention has little risk of side effects on the urinary system, the circulatory system and the digestive system, and exhibits excellent pharmacokinetics, such as oral absorbability etc. Therefore, the compound of the present invention is useful as a superior agent for preventing, treating and/or ameliorating underactive bladder

  由式(I)表示的化合物，其中所有符号的定义与规范中定义的相同，其盐，溶剂化物，前药，与其对映异构体以任意比例混合的混合物，或环糊精包合物具有膀胱去抽搐活性和尿道括约肌松弛活性，它们可以改善膀胱收缩功能障碍和/或尿道松弛功能障碍，例如，对于无力膀胱是有效的。此外，本发明的化合物对泌尿系统、循环系统和消化系统的副作用风险很小，并且表现出优异的药物动力学特性，如口服吸收性等。因此，本发明的化合物可用作预防、治疗和/或改善无力膀胱的优越药物。
• BLOOD FLOW PROMOTERS FOR CAUDA EQUINA TISSUES
  申请人：Ohmoto Kazuyuki

  公开号：US20110015238A1

  公开（公告）日：2011-01-20

  It is intended to provide highly safe and efficacious blood flow promoters for cauda equina tissues. Among prostaglandin-like compounds having a weak hypotensive effect, compounds having an effect of promoting the blood flow in cauda equina tissues (excluding limaprost) are useful as highly safe blood flow promoters for cauda equina tissues and, therefore, are efficacious in preventing and/or treating lumbar pain, lower limb pain, lower limb palsy, intermittent claudication, vesicorectal failure, hypogonadism, etc. caused by cauda equina injuries.

  旨在为马尾神经组织提供高度安全和有效的促进血流剂。在具有弱降压作用的前列腺素类化合物中，具有促进马尾神经组织血流的作用的化合物（不包括利马前列素）作为高度安全的促进马尾神经组织血流的剂，因此，在预防和/或治疗由马尾神经损伤引起的腰痛、下肢疼痛、下肢瘫痪、间歇性跛行、膀胱直肠功能障碍、性腺功能减退等方面具有疗效。
• 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：EP2494990A1

  公开（公告）日：2012-09-05

  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。