(N'-Benzyloxycarbonyl-hydrazino)-acetic acid | 39570-16-6

• 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: (N'-Benzyloxycarbonyl-hydrazino)-acetic acid
• 英文别名: N-carbobenzyloxyaminoglycine；2-(2-phenylmethoxycarbonylhydrazinyl)acetic acid
• CAS: 39570-16-6
• 化学式: C₁₀H₁₂N₂O₄
• 分子量: 224.216
• InChiKey: XHTQOFZNLTUXTF-UHFFFAOYSA-N

物化性质

• 密度：
  1.311±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (N'-Benzyloxycarbonyl-hydrazino)-acetic acid 在 一水合肼 作用下， 以 乙醇 、 水 、 乙酸乙酯 为溶剂， 生成 2-[carbamohydrazonoyl(phenylmethoxycarbonylamino)amino]acetic acid
  参考文献：
  名称：

  Synthesis and Biological Activity of Aminoguanidine and Diaminoguanidine Analogues of the Antidiabetic/Antiobesity Agent 3-Guanidinopropionic Acid

  摘要：

  3-Guanidinopropionic acid (1) has been demonstrated both to improve insulin sensitivity and to promote weight loss selectively from adipose tissue in animal models of non-insulin-dependent diabetes mellitus (NIDDM). However, 1 has also been shown to be a substrate for both the creatine transporter and creatine kinase, leading to marked accumulation in muscle tissue as the corresponding N-phosphate. The corresponding aminoguanidine analogue 2 was recently discovered to retain the antidiabetic activity of 1 while being markedly less susceptible to creatine-like metabolism, suggesting that it should have less potential to accumulate in muscle. Further structural modification of 2 was undertaken to investigate whether the antidiabetic potency could be augmented while maintaining resistance to creatine-like metabolism. Modifications such as a-alkylation, homologation, and bioisosteric replacement of the aminoguanidine all were detrimental to antidiabetic activity. However, the simple regioisomeric aminoguanidinoacetic acid 9 and diaminoguanidinoacetic acid-analogue 7 were found to be equipotent to 2, leading eventually to the discovery of the significantly more potent diaminoguanidinoacetic acid regioisomers 52 and 53. Further attempts to modify the more active template represented by 52 led only to reductions in; antidiabetic activity. Each of the new active analogues displayed the same resistance to creatine-like metabolism as 2. Further testing of 7, 9, and 53 in obese diabetic ob;lob mice confirmed that weight loss is induced selectively from adipose tissue, similar to the lead 1. Administration of 53 to insulin-resistant rhesus monkeys led to reductions in both fasting and post-prandial plasma glucose levels with concomitant reductions in plasma insulin levels, suggesting that the compound improved the action of endogenous insulin. Compounds 7 and 53 were selected for further preclinical development.

  DOI：

  10.1021/jm000094n
• 作为产物：
  描述：

  benzyl 2-(2-ethoxy-2-ethoxyethyl)-1-hydrazinecarboxylate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以87%的产率得到(N'-Benzyloxycarbonyl-hydrazino)-acetic acid
  参考文献：
  名称：

  Synthesis and Biological Activity of Aminoguanidine and Diaminoguanidine Analogues of the Antidiabetic/Antiobesity Agent 3-Guanidinopropionic Acid

  摘要：

  3-Guanidinopropionic acid (1) has been demonstrated both to improve insulin sensitivity and to promote weight loss selectively from adipose tissue in animal models of non-insulin-dependent diabetes mellitus (NIDDM). However, 1 has also been shown to be a substrate for both the creatine transporter and creatine kinase, leading to marked accumulation in muscle tissue as the corresponding N-phosphate. The corresponding aminoguanidine analogue 2 was recently discovered to retain the antidiabetic activity of 1 while being markedly less susceptible to creatine-like metabolism, suggesting that it should have less potential to accumulate in muscle. Further structural modification of 2 was undertaken to investigate whether the antidiabetic potency could be augmented while maintaining resistance to creatine-like metabolism. Modifications such as a-alkylation, homologation, and bioisosteric replacement of the aminoguanidine all were detrimental to antidiabetic activity. However, the simple regioisomeric aminoguanidinoacetic acid 9 and diaminoguanidinoacetic acid-analogue 7 were found to be equipotent to 2, leading eventually to the discovery of the significantly more potent diaminoguanidinoacetic acid regioisomers 52 and 53. Further attempts to modify the more active template represented by 52 led only to reductions in; antidiabetic activity. Each of the new active analogues displayed the same resistance to creatine-like metabolism as 2. Further testing of 7, 9, and 53 in obese diabetic ob;lob mice confirmed that weight loss is induced selectively from adipose tissue, similar to the lead 1. Administration of 53 to insulin-resistant rhesus monkeys led to reductions in both fasting and post-prandial plasma glucose levels with concomitant reductions in plasma insulin levels, suggesting that the compound improved the action of endogenous insulin. Compounds 7 and 53 were selected for further preclinical development.

  DOI：

  10.1021/jm000094n

文献信息

• 1-aminoacetamidopyrroles and 1-amino acetamido-2-(substituted) pyrroles
  申请人：Hoechst Marion Roussel, Inc.

  公开号：US05605925A1

  公开（公告）日：1997-02-25

  There are disclosed 1-aminoacetamidopyrroles and 1-amino-2-(substituted)pyrroles and related compounds of the formula ##STR1## wherein all substituents are defined herein, which are useful as glycine partial agonists and for the enhancement of learning and memory and for the treatment of memory dysfunctions associated with neurodegenerative disorders and are thus indicated in the treatment of Alzheimer's disease and other senile dementias.

  公开了1-氨基乙酰胺基吡咯和1-氨基-2-(取代基)吡咯及其相关化合物的公式##STR1##其中所有取代基的定义如下，它们可用作甘氨酸部分激动剂，用于增强学习和记忆以及治疗与神经退行性疾病相关的记忆功能障碍，因此适用于治疗阿尔茨海默病和其他老年性痴呆症。
• 1-aminoacetamidopyrroles and 1-aminoacetamido-2-(substituted)pyrroles
  申请人：Hoechst-Roussel Pharmaceuticals Inc.

  公开号：US05274116A1

  公开（公告）日：1993-12-28

  There are disclosed 1-aminoacetamidopyrroles and 1-amino-2-(substituted)-pyrroles and related compounds of the formula ##STR1## wherein all substituents are defined herein, which are useful as glycine partial agonists and for the enhancement of learning and memory and for the treatment of memory dysfunctions associated with neurodegenerative disorders and are thus indicated in the treatment of Alzheimer's disease and other senile dementias.

  本文介绍了1-氨基乙酰胺基吡咯和1-氨基-2-(取代基)吡咯及其相关化合物的公开式##STR1##其中所有取代基在此定义，这些化合物可用作甘氨酸部分激动剂，可增强学习和记忆能力，并用于治疗与神经退行性疾病相关的记忆功能障碍，因此适用于治疗阿尔茨海默病和其他老年性痴呆症。
• 1-amino-2-(substituted)pyrroles and related compounds
  申请人：Hoechst Marion Roussel, Inc.

  公开号：US05576446A1

  公开（公告）日：1996-11-19

  There are disclosed 1-aminoacetamidopyrroles and 1-amino-2-(substituted)pyrroles and related compounds of the formula ##STR1## wherein all substituents are defined herein, which are useful as glycine partial agonists and for the enhancement of learning and memory and for treatment of memory dysfunctions associated with neurodegenerative disorders and are thus indicated in the treatment of Alzheimer's disease and other senile dementias.

  公开了1-氨基乙酰胺基吡咯和1-氨基-2-(取代)吡咯及其相关化合物，其化学式如下：##STR1## 其中所有取代基在此处定义，它们可用作甘氨酸部分激动剂，并用于增强学习和记忆以及治疗与神经退行性疾病相关的记忆障碍，因此适用于治疗阿尔茨海默病和其他老年性痴呆症。
• 1-Aminoacetamidopyrroles and 1-amino-2-(substituted) pyrroles and their use for the treatment of neurodegenerative dysfunctions
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0582182A1

  公开（公告）日：1994-02-09

  The present invention relates to compounds of the general formula wherein R₁ ishydrogen or loweralkyl; R₂ ishydrogen, loweralkyl, hydroxyloweralkyl, acyloxyloweralkyl or loweralkoxyloweralkyl; R₃ ishydrogen or loweralkyl; or R₂ and R₃taken together form a cycloalkyl ring of 3 to 7 carbon atoms; R₄ ishydrogen, loweralkyl, aryl or arylloweralkyl; R₅ ishydrogen, loweralkyl, acyl, aryloxycarbonyl, loweralkoxycarbonyl, or arylloweralkoxycarbonyl; X ishydrogen, halogen, cyano, loweralkyl, aryl, arylloweralkyl, hydroxyloweralkyl, arylhydroxyloweralkyl, aminoloweralkyl, loweralkylaminoloweralkyl, diloweralkylaminoloweralkyl, arylsulfonyl, loweralkylsulfonyl; m and n areindependently 0 to 5 with the proviso that the sum of m and n does not exceed 5; p is0, 1 or 2; and wherein the dotted line between the pyrrole ring and the carbonyl group represents an optional bond; when said bond ist present, R₆ is hydrogen, loweralkyl, hydroxy, loweralkoxy, amino, loweralkylamino, diloweralkylamino, or where Y is hydrogen, halogen, loweralkyl, loweralkoxy, hydroxy, trifluormethyl or nitro; or heteroaryl selected from where Z is hydrogen, halogen or loweralkyl, with the proviso that when m and n are each zero and when R₂ and R₃ are each hydrogen and R₆ is phenyl or substituted phenyl and together with he carbonyl group is attached at the 2-position of the pyrrole ring, Y cannot be hydrogen, halogen, trifluoromethyl or nitro; or a pharmaceutically acceptable acid addition salt thereof, or where applicable an optical or geometrical isomer or racemic mixture thereof. The compounds of this invention are useful as glycine partial agonists and for the enhancement of learning and memory and in the treatment of memory dysfunction associated with neurodegenerative disorders and are thus indicated in the treatment of Alzheimer's disease and other senile demantias.

  本发明涉及通式如下的化合物 式中 R₁ 是氢或低级烷基； R₂ 是氢、低级烷基、羟基低级烷基、酰氧基低级烷基或低级烷氧基低级烷基； R₃ 是氢或低级烷基； 或 R₂ 和 R₃ 共同形成 3 至 7 个碳原子的环烷基环； R₄ 是氢、低级烷基、芳基或芳基低级烷基； R₅ 是氢、低级烷基、酰基、芳氧基羰基、低级烷氧基羰基或芳基低级烷氧基羰基； X 是氢、卤素、氰基、低级烷基、芳基、芳基低级烷基、羟基低级烷基、芳基羟基低级烷基、氨基低级烷基、低级烷基氨基低级烷基、稀低级烷基氨基低级烷基、芳基磺酰基、低级烷基磺酰基； m 和 n 分别为 0 至 5，但 m 和 n 之和不超过 5； p 为 0、1 或 2；以及 其中，吡咯环和羰基之间的虚线代表任选键；当所述键存在时，R₆是氢、低级烷基、羟基、低级烷氧基、氨基、低级烷基氨基、稀低级烷基氨基，或 其中 Y 是氢、卤素、低级烷基、低级烷氧基、羟基、三氟甲基或硝基；或选自以下的杂芳基 其中 Z 为氢、卤素或低级烷基，但当 m 和 n 均为零，R₂ 和 R₃ 均为氢，R₆ 为苯基或取代苯基并与羰基一起连接在吡咯环的 2 位时，Y 不能为氢、卤素、三氟甲基或硝基； 或其药学上可接受的酸加成盐，或（如适用）其光学或几何异构体或外消旋混合物。 本发明的化合物可作为甘氨酸部分激动剂，用于增强学习和记忆能力，以及治疗与神经退行性疾病相关的记忆功能障碍，因此适用于治疗阿尔茨海默氏症和其他老年痴呆症。
• US4743685A
  申请人：——

  公开号：US4743685A

  公开（公告）日：1988-05-10