Dimethyl-2-oxo-3,3-propano-7-fluorheptylphosphonat | 69874-02-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: Dimethyl-2-oxo-3,3-propano-7-fluorheptylphosphonat
• 英文别名: dimethyl 2-oxo-3,3-propano-7-fluoroheptylphosphonate；Dimethyl {2-[1-(4-fluorobutyl)cyclobutyl]-2-oxoethyl}phosphonate；2-dimethoxyphosphoryl-1-[1-(4-fluorobutyl)cyclobutyl]ethanone
• CAS: 69874-02-8
• 化学式: C₁₂H₂₂FO₄P
• 分子量: 280.276
• InChiKey: LPEFEPMBYSZQGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Dimethyl-2-oxo-3,3-propano-7-fluorheptylphosphonat 在 sodium tetrahydroborate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 溶剂黄146 为溶剂， 生成
  参考文献：
  名称：

  Discovery of highly potent dual EP 2 and EP 3 agonists with subtype selectivity

  摘要：

  The cyclic carbamate derivatives, 2-{[2-((4S)-4-{(1E,3R)-8-fluoro-3-hydroxy-4,4-dimethyl-1-octenyl}-2-oxo-1,3-oxazolidin-3-yl)ethyl]sulfanyl}-1,3-thiazole-4-carboxylic acid (5) and 2-{[2-((4S)-4-{(1E,3R)-3-[1-(4-fluorobutyl)cyclobutyl]-3-hydroxy-1-propenyl}-2-oxo-1,3-oxazolidin-3-yl)ethyl]sulfanyl}-1,3-thiazole-4-carboxylic acid (7) were identified as the first potent dual EP2 and EP3 agonists with selectivity against the EP1 and EP4 subtypes. Compounds 5 and 7 demonstrated highly potent dual EP2 and EP3 agonist activity with EC50 values of 10 nM or less. In addition, these compounds possess structural features distinct from natural prostaglandins, such as a cyclic carbamate moiety, a dimethyl or cyclobutyl group and a terminal fluorine atom. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.12.039
• 作为产物：
  描述：

  在 正丁基锂 、 氯化亚砜 作用下， 以 四氢呋喃 为溶剂， 生成 Dimethyl-2-oxo-3,3-propano-7-fluorheptylphosphonat
  参考文献：
  名称：

  Discovery of highly potent dual EP 2 and EP 3 agonists with subtype selectivity

  摘要：

  The cyclic carbamate derivatives, 2-{[2-((4S)-4-{(1E,3R)-8-fluoro-3-hydroxy-4,4-dimethyl-1-octenyl}-2-oxo-1,3-oxazolidin-3-yl)ethyl]sulfanyl}-1,3-thiazole-4-carboxylic acid (5) and 2-{[2-((4S)-4-{(1E,3R)-3-[1-(4-fluorobutyl)cyclobutyl]-3-hydroxy-1-propenyl}-2-oxo-1,3-oxazolidin-3-yl)ethyl]sulfanyl}-1,3-thiazole-4-carboxylic acid (7) were identified as the first potent dual EP2 and EP3 agonists with selectivity against the EP1 and EP4 subtypes. Compounds 5 and 7 demonstrated highly potent dual EP2 and EP3 agonist activity with EC50 values of 10 nM or less. In addition, these compounds possess structural features distinct from natural prostaglandins, such as a cyclic carbamate moiety, a dimethyl or cyclobutyl group and a terminal fluorine atom. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.12.039

文献信息

• Prostaglandin analogues
  申请人：Ono Pharmaceutical Co. Ltd.

  公开号：US04208428A1

  公开（公告）日：1980-06-17

  The invention relates to prostaglandin analogues of the general formula: ##STR1## (wherein A represents a grouping of the formula: ##STR2## B represents an alkylene group containing from 1 to 7 carbon atoms or a group ##STR3## (wherein the group --(CH.sub.2).sub.n --may be attached to the ortho, meta or para position of the phenyl ring and m and n, which may be the same or different, each represent an integer from 1 to 5 inclusive, the sum of the integers represented by m and n being from 2 to 6 inclusive), X represents ethylene or cis-vinylene, Y represents ethylene or trans-vinylene, W represents ethylene or trans-vinylene, Z represents a halogen atom, and R.sup.1 represents a hydrogen atom or an alkyl group containing from 1 to 12 carbon atoms) and cyclodextrin clathrates of such acids and esters and, when R.sup.1 represents a hydrogen atom, non-toxic salts thereof, which possess characteristic prostaglandin-like properties.

  该发明涉及一般式的前列腺素类似物：##STR1##（其中A代表式的分组：##STR2## B代表含有1至7个碳原子的烷基基团或##STR3##（其中基团--(CH.sub.2).sub.n--可以连接到苯环的邻位、间位或对位，m和n，可以相同也可以不同，每个代表从1到5的整数，由m和n代表的整数之和从2到6，X代表乙烯或顺式乙烯基，Y代表乙烯或反式乙烯基，W代表乙烯或反式乙烯基，Z代表卤素原子，R.sup.1代表氢原子或含有1到12个碳原子的烷基基团）以及这些酸和酯的环糊精包合物，当R.sup.1代表氢原子时，其非毒性盐，具有类似前列腺素的特性。
• Blood flow promoters for cauda equina tissues
  申请人：Ohmoto Kazuyuki

  公开号：US08501793B2

  公开（公告）日：2013-08-06

  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.

  本发明旨在提供高度安全和有效的促进马尾神经组织血流的药物。在具有轻微降压作用的前列腺素类似物中，具有促进马尾神经组织血流作用的化合物（不包括利马普罗斯特）是高度安全的促进马尾神经组织血流的药物，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。
• 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。
• US4208428A
  申请人：——

  公开号：US4208428A

  公开（公告）日：1980-06-17
• Discovery of highly potent dual EP 2 and EP 3 agonists with subtype selectivity
  作者：Akihiro Kinoshita、Masato Higashino、Yoshiyuki Aratani、Akito Kakuuchi、Hidekazu Matsuya、Kazuyuki Ohmoto

  DOI：10.1016/j.bmcl.2015.12.039

  日期：2016.2

  The cyclic carbamate derivatives, 2-[2-((4S)-4-(1E,3R)-8-fluoro-3-hydroxy-4,4-dimethyl-1-octenyl}-2-oxo-1,3-oxazolidin-3-yl)ethyl]sulfanyl}-1,3-thiazole-4-carboxylic acid (5) and 2-[2-((4S)-4-(1E,3R)-3-[1-(4-fluorobutyl)cyclobutyl]-3-hydroxy-1-propenyl}-2-oxo-1,3-oxazolidin-3-yl)ethyl]sulfanyl}-1,3-thiazole-4-carboxylic acid (7) were identified as the first potent dual EP2 and EP3 agonists with selectivity against the EP1 and EP4 subtypes. Compounds 5 and 7 demonstrated highly potent dual EP2 and EP3 agonist activity with EC50 values of 10 nM or less. In addition, these compounds possess structural features distinct from natural prostaglandins, such as a cyclic carbamate moiety, a dimethyl or cyclobutyl group and a terminal fluorine atom. (C) 2015 Elsevier Ltd. All rights reserved.