N-(3-nitrobenzyl)glycine ethylester | 179414-48-3

• 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-(3-nitrobenzyl)glycine ethylester
• 英文别名: Ethyl 2-[(3-nitrophenyl)methylamino]acetate
• CAS: 179414-48-3
• 化学式: C₁₁H₁₄N₂O₄
• mdl: MFCD12607719
• 分子量: 238.243
• InChiKey: NMRKFJFZSCWTJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3-nitrobenzyl)glycine ethylester 在 盐酸 、 溶剂黄146 作用下， 以 乙醚 为溶剂， 反应 20.0h， 生成 1-(3-nitrobenzyl)-2,4-dioxoimidazolidine-3-acetic acid
  参考文献：
  名称：

  Highly Selective Aldose Reductase Inhibitors. 3. Structural Diversity of 3-(Arylmethyl)-2,4,5-trioxoimidazolidine-1-acetic Acids

  摘要：

  Accumulation of intracellular sorbitol, the reduced product of glucose, catalyzed by aldose reductase (AR) (EC 1.1.1.21), is thought to be the cause of the development of diabetic complications. Our attention is focused on finding compounds which inhibit AR without significantly inhibiting aldehyde reductase (ALR) (EC 1.1.1.2). The uracil or 2,4-dioxoimidazolidine skeleton having the benzothiazolyl or 4-chloro-3-nitrophenyl group as an aryl part indicated not only extremely high AR inhibitory activity but also AR selectivity. The ratio of IC50(ALR)/IC50(AR) of 3-[(5-chlorobenzothiazol-2-yl)methyl]-1,2,3,4-tetrahydro-2,4-dioxopyrim-idine-1-acetic acid (47d) was more than 17 500. The uracil skeleton with the benzothiazolyl moiety seemed to be the best combination for selective AR inhibition.

  DOI：

  10.1021/jm960594+
• 作为产物：
  描述：

  甘氨酸乙酯盐酸盐 、 间硝基苯甲醛 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 62.0h， 以35%的产率得到N-(3-nitrobenzyl)glycine ethylester
  参考文献：
  名称：

  尿失禁治療薬

  摘要：

  要解决的问题：提供一种新的更安全的化合物，具有更高的抗尿失禁效果，且副作用更小。解决方案：用于尿失禁的预防和/或治疗剂包括以下式(I)所表示的化合物，其中，A是一个单键或亚甲基；E和G分别是可能被低烷基取代的较低直链烷基；m为0-5；R1为卤素、CF3、OCF3、CN、NO2、羧基、羟基、硫氢基、较低烷氧羰基、（取代）氨基甲酰基、较低烷酰氧基、（取代）磺胺基团或可能被ORa（其中，Ra为H或较低烷基）、COORa、SRa或N（Ra）2取代的较低烷基或类似物；R2、R3和R4分别为H或较低烷基；n为0-5；R5分别为CN、NO2、COOH、SO3H、较低烷氧羰基、较低烷酰基或类似物；R6和R7分别为H或可能被ORa或COOH取代的较低烷基；或NR6R7为5-至6-成员饱和杂环环，光学活性物质或其药理学上可接受的盐作为活性成分。该药物对于治疗和/或预防尿失禁表现出优异效果，而不会对心血管系统如血压升高等造成不良影响。版权所有：（C）2005，JPO&NCIPI

  公开号：

  JP2005200303A

文献信息

• 尿失禁治療薬
  申请人：——

  公开号：JP2005200303A

  公开（公告）日：2005-07-28

  PROBLEM TO BE SOLVED: To provide a new higher safe compound having higher effectiveness against urinary incontinence with smaller adverse effects.

  SOLUTION: A prophylactic and/or therapeutic agent for the urinary incontinence comprises a compound represented by formula (I) äwherein, A is a single bond or methylene; E and G are each a lower straight-chain alkylene which may be substituted with a lower alkyl; m is 0-5; R1s are each a halogen, a CF3, an OCF3, a CN, an NO2, a carboxy, an OH, an SH, a lower alkoxycarbonyl, a (substituted) carbamoyl, a lower alkanoyloxy, a (substituted) sulfamoyl group or a lower alkyl group or the like which may be substituted with an ORa (wherein, Ra is an H or a lower alkyl), a COORa, an SRa or an N(Ra)2; R2, R3and R4are each an H or a lower alkyl; n is 0-5; R5s are each a CN, an NO2, a COOH, an SO3H, a lower alkoxycarbonyl, a lower alkanoyl or the like; R6and R7are each an H or a lower alkyl which may be substituted with an ORa or a COOH; or an NR6R7is a 5- to a 6-membered saturated heterocyclic ring}, an optically active substance or a pharmacologically acceptable salt thereof as an active ingredient. The drug exhibits excellent effects on treatment and/or prophylaxis of the urinary incontinence without causing adverse effects on the cardiovacular system such as blood pressure elevation.

  COPYRIGHT: (C)2005,JPO&NCIPI

  要解决的问题：提供一种新的更安全的化合物，具有更高的抗尿失禁效果，且副作用更小。解决方案：用于尿失禁的预防和/或治疗剂包括以下式(I)所表示的化合物，其中，A是一个单键或亚甲基；E和G分别是可能被低烷基取代的较低直链烷基；m为0-5；R1为卤素、CF3、OCF3、CN、NO2、羧基、羟基、硫氢基、较低烷氧羰基、（取代）氨基甲酰基、较低烷酰氧基、（取代）磺胺基团或可能被ORa（其中，Ra为H或较低烷基）、COORa、SRa或N（Ra）2取代的较低烷基或类似物；R2、R3和R4分别为H或较低烷基；n为0-5；R5分别为CN、NO2、COOH、SO3H、较低烷氧羰基、较低烷酰基或类似物；R6和R7分别为H或可能被ORa或COOH取代的较低烷基；或NR6R7为5-至6-成员饱和杂环环，光学活性物质或其药理学上可接受的盐作为活性成分。该药物对于治疗和/或预防尿失禁表现出优异效果，而不会对心血管系统如血压升高等造成不良影响。版权所有：（C）2005，JPO&NCIPI
• MACROCYCLIC FACTOR VIIA INHIBITORS USEFUL AS ANTICOAGULANTS
  申请人：Wurtz Nicholas Ronald

  公开号：US20100113488A1

  公开（公告）日：2010-05-06

  The present invention relates generally to novel macrocycles of Formula (I): or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein the variables A, B, C, D, L, M, W, Z 1 , Z 2 , Z 3 , Z 4 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 are as defined herein. These compounds are selective inhibitors of factor VIIa which can be used as medicaments.
• US8420830B2
  申请人：——

  公开号：US8420830B2

  公开（公告）日：2013-04-16
• [EN] MACROCYCLIC FACTOR VIIA INHIBITORS USEFUL AS ANTICOAGULANTS<br/>[FR] INHIBITEURS MACROCYCLIQUES DU FACTEUR VIIA UTILES EN TANT QU'ANTICOAGULANTS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2008079836A2

  公开（公告）日：2008-07-03

  (EN) The present invention relates generally to novel macrocycles of Formula (I) or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein the variables A, B, C, D, L, M, W, Z1, Z2, Z3, Z4, R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are as defined herein. These compounds are selective inhibitors of factor VIIa which can be used as medicaments.(FR) La présente invention concerne de nouveaux macrocycles représentés par la formule (I) ou des stéréoisomères, des tautomères, des sels, des solvates ou des précurseurs de médicament pharmaceutiquement acceptables de ces derniers, dans lesquels les variables A, B, C, D, L, M, W, Z1, Z2, Z3, Z4, R1, R2, R3, R4, R5, R6, R7, R8, R9et R10 sont telles que définies dans le descriptif. Ces composés sont des inhibiteurs sélectifs du facteur VIIa qui peuvent être utilisés en tant que médicaments.
• 10.1002/cmdc.202400139
  作者：Milite, Ciro、Sarno, Giuliana、Pacilio, Ida、Cianciulli, Agostino、Viviano, Monica、Iannelli, Giulia、Gazzillo, Erica、Feoli, Alessandra、Cipriano, Alessandra、Giovanna Chini, Maria、Castellano, Sabrina、Bifulco, Giuseppe、Sbardella, Gianluca

  DOI：10.1002/cmdc.202400139

  日期：——

  AbstractProtein arginine methyltransferase (PRMT) 4 (also known as coactivator‐associated arginine methyltransferase 1; CARM1) is involved in a variety of biological processes and is considered as an emerging target class in oncology and other diseases. A successful strategy to identify PRMT substrate‐competitive inhibitors has been to exploit chemical scaffolds able to mimic the arginine substrate. (S)‐Alanine amide moiety is a valuable arginine mimic for the development of potent and selective PRMT4 inhibitors; however, its high hydrophilicity led to derivatives with poor cellular outcomes. Here, we describe the development of PRMT4 inhibitors featuring a central pyrrole core and an alanine amide moiety. Rounds of optimization, aimed to increase lipophilicity and simultaneously preserve the inhibitory activity, produced derivatives that, despite good potency and physicochemical properties, did not achieve on‐target effects in cells. On the other hand, masking the amino group with a NAD(P)H:quinone oxidoreductase 1 (NQO1)‐responsive trigger group, led to prodrugs able to reduce arginine dimethylation of the PRMT4 substrates BRG1‐associated factor 155 (BAF155). These results indicate that prodrug strategies can be successfully applied to alanine‐amide containing PRMT4 inhibitors and provide an option to enable such compounds to achieve sufficiently high exposures in vivo.