2-benzyloxymethyl-4-[(4-methylbenzoyl)amino]butanoic acid | 861819-90-1

• 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: 2-benzyloxymethyl-4-[(4-methylbenzoyl)amino]butanoic acid
• 英文别名: 2-Benzyloxymethyl-4-(N-(4-methylphenylcarbonyl)amino)butyric acid；4-[(4-methylbenzoyl)amino]-2-(phenylmethoxymethyl)butanoic acid
• CAS: 861819-90-1
• 化学式: C₂₀H₂₃NO₄
• 分子量: 341.407
• InChiKey: PKBDEULZMLFZJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-benzyloxymethyl-4-[(4-methylbenzoyl)amino]butanoic acid 在 palladium on activated charcoal 氢气 、 三溴化硼 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-Hydroxy-2-hydroxymethyl-4-(N-(4-methylphenylcarbonyl)amino)butyramide
  参考文献：
  名称：

  Novel matrix metalloproteinase inhibitors: Generation of lead compounds by the in silico fragment-based approach

  摘要：

  Generation of structurally new matrix metalloproteinase inhibitors was successfully carried out using an in silico technique. In order to identify the small fragment interacting with residues in the S1' pocket of MMP-1 through hydrogen bonds, we performed in silico screening using the LUDI program. As a result, acetyl-L-alanyl-(N-methyl)amide (AC-L-Ala-NHMe) was selected to link with another fragment, hydroxamic acid that interacted with catalytic zinc. By this approach, the L-glutamic acid derivative 2b was discovered to be a new type of matrix metalloproteinase inhibitor. Further transformation to reduce its peptidic nature and improve activity yielded nonpeptidic lead compounds as inhibitors of MMP-1, -2, -3, and -9. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.051
• 作为产物：
  描述：

  对甲基苯甲酰氯 在 sodium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 六甲基磷酰三胺 、 正己烷 、 水 为溶剂， 反应 5.0h， 生成 2-benzyloxymethyl-4-[(4-methylbenzoyl)amino]butanoic acid
  参考文献：
  名称：

  Novel matrix metalloproteinase inhibitors: Generation of lead compounds by the in silico fragment-based approach

  摘要：

  Generation of structurally new matrix metalloproteinase inhibitors was successfully carried out using an in silico technique. In order to identify the small fragment interacting with residues in the S1' pocket of MMP-1 through hydrogen bonds, we performed in silico screening using the LUDI program. As a result, acetyl-L-alanyl-(N-methyl)amide (AC-L-Ala-NHMe) was selected to link with another fragment, hydroxamic acid that interacted with catalytic zinc. By this approach, the L-glutamic acid derivative 2b was discovered to be a new type of matrix metalloproteinase inhibitor. Further transformation to reduce its peptidic nature and improve activity yielded nonpeptidic lead compounds as inhibitors of MMP-1, -2, -3, and -9. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.051

文献信息

• Aminobutyric acid derivatives
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：US06420427B1

  公开（公告）日：2002-07-16

  An aminobutyric acid derivative of the formula (I): (wherein all symbols are as defined in the specification) and salt thereof. salt thereof. The compounds of the formula (I) possess an inhibitory activity on matrix metalloproteinase and are useful for prevention and/or treatment of diseases, for example, rheumatoid diseases, arthrosteitis, unusual bone resorption, osteoporosis, periodontitis, interstitial nephritis, arteriosclerosis, pulmonary emphysema, cirrhosis, cornea injury, metastasis of, invasion of or growth of tumor cells, autoimmune disease (e.g. Crohn's disease, Sjogren's syndrome), disease caused by vascular emigration or infiltration of leukocytes, arterialization, multiple sclerosis, aorta aneurysm, endometriosis.

  化合物的公式(I)为氨基丁酸衍生物：（其中所有符号均如规范中定义），以及其盐。公式(I)的化合物具有对基质金属蛋白酶的抑制活性，并可用于预防和/或治疗疾病，例如风湿性疾病，关节炎，异常骨吸收，骨质疏松症，牙周炎，间质性肾炎，动脉硬化，肺气肿，肝硬化，角膜损伤，肿瘤细胞的转移、侵袭或生长，自身免疫性疾病（例如克隆病，Sjogren综合征），由血管移民或白细胞浸润引起的疾病，动脉化，多发性硬化症，主动脉瘤，子宫内膜异位症。
• AMINOBUTANOIC ACID DERIVATIVES
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1024134A1

  公开（公告）日：2000-08-02

  An aminobutyric acid derivative of the formula (I): (wherein all symbols are as defined in the specification) and salt thereof. salt thereof. The compounds of the formula (I) possess an inhibitory activity on matrix metalloproteinase and are useful for prevention and / or treatment of diseases, for example, rheumatoid diseases, arthrosteitis, unusual bone resorption, osteoporosis, periodontitis, interstitial nephritis, arteriosclerosis, pulmonary emphysema, cirrhosis, cornea injury, metastasis of, invasion of or growth of tumor cells, autoimmune disease (e.g. Crohn's disease, Sjogren's syndrome), disease caused by vascular emigration or infiltration of leukocytes, arterialization, multiple sclerosis, aorta aneurysm, endometriosis.

  式（I）的氨基丁酸衍生物： (其中所有符号如说明书中所定义）及其盐。 式（I）化合物对基质金属蛋白酶具有抑制活性，可用于预防和/或治疗疾病，例如类风湿病、关节炎、异常骨吸收、骨质疏松症、牙周炎、间质性肾炎、动脉硬化、肺气肿、肝硬化、角膜损伤、肿瘤细胞的转移、侵入或生长、自身免疫性疾病（如克罗恩病、Sj.如克罗恩病、Sjogren 综合症）、血管移位或白细胞浸润引起的疾病、动脉化、多发性硬化、主动脉瘤、子宫内膜异位症。
• US6420427B1
  申请人：——

  公开号：US6420427B1

  公开（公告）日：2002-07-16
• Novel matrix metalloproteinase inhibitors: Generation of lead compounds by the in silico fragment-based approach
  作者：Kanji Takahashi、Masahiro Ikura、Hiromu Habashita、Minoru Nishizaki、Tsuneyuki Sugiura、Shingo Yamamoto、Shingo Nakatani、Koji Ogawa、Hiroyuki Ohno、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmc.2005.04.051

  日期：2005.7

  Generation of structurally new matrix metalloproteinase inhibitors was successfully carried out using an in silico technique. In order to identify the small fragment interacting with residues in the S1' pocket of MMP-1 through hydrogen bonds, we performed in silico screening using the LUDI program. As a result, acetyl-L-alanyl-(N-methyl)amide (AC-L-Ala-NHMe) was selected to link with another fragment, hydroxamic acid that interacted with catalytic zinc. By this approach, the L-glutamic acid derivative 2b was discovered to be a new type of matrix metalloproteinase inhibitor. Further transformation to reduce its peptidic nature and improve activity yielded nonpeptidic lead compounds as inhibitors of MMP-1, -2, -3, and -9. (c) 2005 Elsevier Ltd. All rights reserved.