N-benzyl-N-(diethoxyphosphorylmethyl)glycine ethyl ester | 98832-20-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-benzyl-N-(diethoxyphosphorylmethyl)glycine ethyl ester
• 英文别名: ethyl 2-(benzyl((diethoxyphosphoryl)methyl)amino)acetate；Ethyl-N-benzyl-N-diethylphosphonomethyl-glycinate；ethyl 2-[benzyl(diethoxyphosphorylmethyl)amino]acetate
• CAS: 98832-20-3
• 化学式: C₁₆H₂₆NO₅P
• 分子量: 343.36
• InChiKey: PAWXSKGAPVBUBA-UHFFFAOYSA-N

物化性质

• 沸点：
  426.3±35.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-benzyl-N-(diethoxyphosphorylmethyl)glycine ethyl ester 在 碘代三甲硅烷 、 palladium 10% on activated carbon 、 甲酸铵 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 2'-deoxyadenosine-5'-[(phosphonomethyl) glycine ethyl ester] phosphoramidate
  参考文献：
  名称：

  亚氨基丙酸是通过HIV-1逆转录酶进行DNA聚合的离去基团

  摘要：

  焦磷酸酯模拟物：脱氧腺苷单磷酸酯类似物的亚氨基二乙酸氨基磷酸酯，在氨基酸功能上带有延伸的脂肪链或膦酸部分，可作为HIV-1逆转录酶的潜在底物。发现亚氨基二丙酸是焦磷酸盐的极佳模拟物。

  DOI：

  10.1002/cbic.201100160
• 作为产物：
  描述：

  1,3,5-三苄基六氢-1,3,5-三嗪 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 4.5h， 生成 N-benzyl-N-(diethoxyphosphorylmethyl)glycine ethyl ester
  参考文献：
  名称：

  亚氨基丙酸是通过HIV-1逆转录酶进行DNA聚合的离去基团

  摘要：

  焦磷酸酯模拟物：脱氧腺苷单磷酸酯类似物的亚氨基二乙酸氨基磷酸酯，在氨基酸功能上带有延伸的脂肪链或膦酸部分，可作为HIV-1逆转录酶的潜在底物。发现亚氨基二丙酸是焦磷酸盐的极佳模拟物。

  DOI：

  10.1002/cbic.201100160
• 作为试剂：
  描述：

  diethyl N-benzylaminomethylphosphonate 、 N,N-二异丙基乙胺 、 溴乙酸乙酯 在 N-benzyl-N-(diethoxyphosphorylmethyl)glycine ethyl ester 作用下， 以 乙腈 为溶剂， 反应 6.5h， 以This resulted in 8.0 g (50%) of ethyl 2-(benzyl((diethoxyphosphoryl)methyl)amino)acetate as yellow oil的产率得到N-benzyl-N-(diethoxyphosphorylmethyl)glycine ethyl ester
  参考文献：
  名称：

  Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders

  摘要：

  本公开涉及化合物和治疗液体潴留或盐过量相关疾病的方法，如心力衰竭（尤其是充血性心力衰竭）、慢性肾脏病、终末期肾脏病、肝病和过氧化物酶体增殖物激活受体（PPAR）γ激动剂引起的液体潴留。本公开还涉及化合物和治疗高血压的方法。本公开还涉及化合物和治疗胃肠道疾病的方法，包括治疗或减轻与胃肠道疾病相关的疼痛。

  公开号：

  US08541448B2

文献信息

• COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS
  申请人：Charmot Dominique

  公开号：US20120263670A1

  公开（公告）日：2012-10-18

  The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

  本公开涉及化合物和方法，用于治疗与液体潴留或盐过载相关的疾病，如心力衰竭（特别是充血性心力衰竭）、慢性肾脏病、终末期肾脏病、肝病和过氧化物酶体增殖物激活受体（PPAR）γ激动剂引起的液体潴留。本公开还涉及化合物和方法，用于治疗高血压。本公开还涉及化合物和方法，用于治疗胃肠道疾病，包括治疗或减轻与胃肠道疾病相关的疼痛。
• COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDER
  申请人：Ardelyx, Inc.

  公开号：US20150190389A1

  公开（公告）日：2015-07-09

  The present disclosure is directed to compounds of the structure (X): CoreL-NHE) n (X) wherein: n is 2 or 3; NHE has the structure wherein: R 1 is H or —SO 2 —NR 7 R 8 —; R 2 is selected from H, —NR 7 (CO)R 8 , —SO 2 —NR 7 R 8 — and —NR 7 R 8 ; R 3 is hydrogen; R 7 is hydrogen; R 8 is a bond linking to L; L is a polyalkylene glycol linker; and Core has the following structure: wherein: X is selected from the group consisting of a bond, —O—, —NH—, NHC(═O)—, —NHC(═O)NH— and —NHSO 2 —; and Y is selected from the group consisting of a bond, optionally substituted C 1-6 alkylene, optionally substituted benzene, pyridinyl, a polyethylene glycol linker and —(CH 2 ) 1-6 O(CH 2 ) 1-6 —, and methods of using such compounds for the treatment of irritable bowel syndrome, chronic kidney disease and end-stage renal disease.

  本公开涉及结构为（X）：CoreL-NHE)n（X）的化合物，其中：n为2或3；NHE具有以下结构：其中：R1为H或—SO2—NR7R8—；R2选自H，—NR7（CO）R8，—SO2—NR7R8—和—NR7R8；R3为氢；R7为氢；R8为连接到L的键；L为多聚乙二醇连接剂；Core具有以下结构：其中：X选自由键，—O—，—NH—，NHC（═O）—，—NHC（═O）NH—和—NHSO2—；Y选自键，可选择性地取代的C1-6烷基，可选择性地取代的苯，吡啶基，聚乙二醇连接剂和—（CH2）1-6O（CH2）1-6—，以及使用这种化合物治疗肠易激综合征、慢性肾脏病和终末期肾脏疾病的方法。
• Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorder
  申请人：Ardelyx, Inc.

  公开号：US09408840B2

  公开（公告）日：2016-08-09

  The present disclosure is directed to compounds of the structure (X): CoreL-NHE)n  (X) wherein: n is 2 or 3; NHE has the structure wherein: R1 is H or —SO2—NR7R8—; R2 is selected from H, —NR7(CO)R8, —SO2—NR7R8— and —NR7R8; R3 is hydrogen; R7 is hydrogen; R8 is a bond linking to L; L is a polyalkylene glycol linker; and Core has the following structure: wherein: X is selected from the group consisting of a bond, —O—, —NH—, NHC(═O)—, —NHC(═O)NH— and —NHSO2—; and Y is selected from the group consisting of a bond, optionally substituted C1-6 alkylene, optionally substituted benzene, pyridinyl, a polyethylene glycol linker and —(CH2)1-6O(CH2)1-6—, and methods of using such compounds for the treatment of irritable bowel syndrome, chronic kidney disease and end-stage renal disease.

  本公开涉及结构式（X）：CoreL-NHE)n  (X)的化合物，其中：n为2或3；NHE具有以下结构：其中：R1为H或—SO2—NR7R8—；R2选自H，—NR7（CO）R8，—SO2—NR7R8—和—NR7R8；R3为氢；R7为氢；R8为连接到L的键；L为多聚乙二醇连接体；Core具有以下结构：其中：X选自由键，—O—，—NH—，NHC（═O）—，—NHC（═O）NH—和—NHSO2—；Y选自自由键，可选取代的C1-6烷基，可选取代的苯，吡啶基，多聚乙二醇连接体和—（CH2）1-6O（CH2）1-6—，以及使用这种化合物治疗肠易激综合征、慢性肾脏疾病和终末期肾脏疾病的方法。
• COMBINATIONS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS
  申请人：Ardelyx, Inc.

  公开号：EP3939964A1

  公开（公告）日：2022-01-19

  The present disclosure is directed to a pharmaceutical composition comprising a compound of formula (X), in combination with another active agent, and to the use of said composition in methods for the treatment of disorders associated with fluid retention or salt overload or gastrointestinal tract disorders, such as irritable bowel syndrome and constipation associated with cystic fibrosis. The methods generally comprise administering to a mammal in need thereof a pharmaceutical composition comprising such a compound, that is designed to be substantially active in the gastrointestinal (GI) tract to inhibit NHE-mediated antiport of sodium ions and hydrogen ions therein. More particularly, the method comprises administering to a mammal in need thereof a pharmaceutical composition comprising such a compound, that inhibits NHE-3, -2 and/or -8 mediated antiport of sodium and/or hydrogen ions in the GI tract and is designed to be substantially impermeable to the layer of epithelial cells, or more specifically the epithelium of the GI tract. As a result of the compound being substantially impermeable, it is not absorbed and is thus essentially systemically non-bioavailable, so as to limit the exposure of other internal organs (e.g., liver, heart, brain, etc.) thereto.

  本公开涉及一种药物组合物，该组合物包含与另一种活性剂组合的式(X)化合物，并涉及将所述组合物用于治疗与体液潴留或盐超载相关的疾病或胃肠道疾病（如肠易激综合征和与囊性纤维化相关的便秘）的方法。这些方法一般包括向有需要的哺乳动物施用包含此类化合物的药物组合物，该组合物设计为在胃肠道（GI）中基本活跃，以抑制其中钠离子和氢离子的 NHE 介导的反转运。更具体地说，该方法包括向有需要的哺乳动物施用包含这种化合物的药物组合物，该化合物可抑制胃肠道中NHE-3、-2和/或-8介导的钠离子和/或氢离子的反转运，并且设计成基本上不渗透到上皮细胞层，或更具体地说，不渗透到胃肠道上皮细胞层。由于该化合物基本上不渗透，因此不会被吸收，从而基本上不会被全身生物利用，从而限制了其他内脏器官（如肝脏、心脏、大脑等）对该化合物的接触。
• [EN] COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS<br/>[FR] COMPOSÉS ET PROCÉDÉS D'INHIBITION D'UN ANTIPORT À MÉDIATION PAR NHE DANS LE TRAITEMENT DE TROUBLES ASSOCIÉS À UNE RÉTENTION DE FLUIDE OU À UNE SURCHARGE DE SEL ET DE TROUBLES DU TRACTUS GASTRO-INTESTINAL
  申请人：ARDELYX INC

  公开号：WO2010078449A3

  公开（公告）日：2010-09-30