(4-aminomethyl-benzyl)-phosphonic acid diethyl ester | 93041-76-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4-aminomethyl-benzyl)-phosphonic acid diethyl ester
• 英文别名: (4-Aminomethyl-benzyl)-phosphonsaeure-diaethylester；diethyl 4-(aminomethyl)benzylphosphonate；Diethyl {[4-(aminomethyl)phenyl]methyl}phosphonate；[4-(diethoxyphosphorylmethyl)phenyl]methanamine
• CAS: 93041-76-0
• 化学式: C₁₂H₂₀NO₃P
• 分子量: 257.269
• InChiKey: XPOIKMLBIZHKSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-aminomethyl-benzyl)-phosphonic acid diethyl ester 在 环氧乙烷 作用下， 生成 (4-{[bis-(2-chloro-ethyl)-amino]-methyl}-benzyl)-phosphonic acid diethyl ester
  参考文献：
  名称：

  Nitrogen Mustard Derivatives Containing the Phosphonate Group¹

  摘要：

  DOI：

  10.1021/ja01521a029
• 作为产物：
  描述：

  diethyl 4-(bromomethyl)benzylphosphonate 在 sodium azide 、 三苯基膦 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 (4-aminomethyl-benzyl)-phosphonic acid diethyl ester
  参考文献：
  名称：

  Non-peptide itam mimics as ZAP-70 antagonists

  摘要：

  Non-peptide bidentate ITAM mimics as ZAP-70 antagonists have been prepared by accommodating non-hydrolyzable phosphotyrosine analogues at each end of a non-peptide spacer with a maximal P-P distance of 39 Angstrom. The most potent antagonist 5 had an IC50=0.25 mu M against ZAP-70 with good cellular activity. Monodentates were ca. 10-fold weaker antagonists with improved cell permeability. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)10102-0

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 THERAPEUTIC USES THEREOF
  申请人：Willardsen J. Adam

  公开号：US20120329786A1

  公开（公告）日：2012-12-27

  The invention relates to compounds, pharmaceutical compositions and methods useful for treating cancer, systemic or chronic inflammation, rheumatoid arthritis, diabetes, obesity, T-cell mediated autoimmune disease, ischemia, and other complications associated with these diseases and disorders.

  本发明涉及化合物、药物组合物和方法，用于治疗癌症、全身或慢性炎症、类风湿性关节炎、糖尿病、肥胖症、T细胞介导的自身免疫性疾病、缺血以及与这些疾病和疾病相关的其他并发症。
• 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。
• Synthesis and Biological Studies of Novel Aminophosphonates and Their Metal Carbonyl Complexes (Fe, Ru)
  作者：Aneta Kosińska、David Virieux、Jean-Luc Pirat、Kamila Czarnecka、Małgorzata Girek、Paweł Szymański、Sławomir Wojtulewski、Saranya Vasudevan、Arkadiusz Chworos、Bogna Rudolf

  DOI：10.3390/ijms23158091

  日期：——

  strategy to introduce new drug candidates for the treatment of neurodegenerative diseases. A series of (aminomethyl)benzylphosphonates 8a–c and their metallocarbonyl iron 9a–c and ruthenium 10a–c complexes were designed, synthesized, and evaluated for their inhibitory potentials against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) by determination of IC50. Metallocarbonyl derivatives

  寻找生物相关靶点的新抑制剂被认为是引入新的候选药物治疗神经退行性疾病的重要策略。设计、合成了一系列（氨基甲基）苄基膦酸盐8a - c及其金属羰基铁9a - c和钌10a - c配合物，并通过 IC 50测定评估了它们对乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE) 的抑制潜力。一般来说，金属羰基衍生物对这些酶没有显着的抑制活性，最有效的抑制剂是（氨基甲基）苄基膦酸酯8a（针对 AChE 的 IC 50 = 1.215 µM）。与异构体8b和8c相比，AChE 和（氨基甲基）苄基膦酸酯8a – c的分子对接分析显示8a和 AChE的相互作用最强。还进行并讨论了合成化合物对 V79 细胞系的细胞毒性研究。
• 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。