3-(2-(二乙氧基磷酰基)-2-(萘-1-基)乙酰基)-2-萘甲酸 | 429676-95-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: 3-(2-(二乙氧基磷酰基)-2-(萘-1-基)乙酰基)-2-萘甲酸
• 英文名称: 3-(2-Diethoxyphosphoryl-2-naphthalen-1-ylacetyl)naphthalene-2-carboxylic acid
• CAS: 429676-95-9
• 化学式: C₂₇H₂₅O₆P
• 分子量: 476.466
• InChiKey: IQGJVCNTPPAPQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(2-(二乙氧基磷酰基)-2-(萘-1-基)乙酰基)-2-萘甲酸 在 吡啶 、 三甲基溴硅烷 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 54.5h， 生成 [2-(3-{[(2,2-Diphenyl-ethylcarbamoyl)-methyl]-methyl-carbamoyl}-naphthalen-2-yl)-1-naphthalen-1-yl-2-oxo-ethyl]-phosphonic acid
  参考文献：
  名称：

  Nonpeptide Inhibitors of Cathepsin G:  Optimization of a Novel β-Ketophosphonic Acid Lead by Structure-Based Drug Design

  摘要：

  The serine protease cathepsin G (EC 3.4.21.20; Cat G), which is stored in the azurophilic granules of neutrophils (polymorphonuclear leukocytes) and released on degranulation, has been implicated in various pathological conditions associated with inflammation. By employing high-throughput screening, we identified beta-ketophosphonic acid 1 as a moderate inhibitor of Cat G (IC(50) = 4.1 microM). We were fortunate to obtain a cocrystal of 1 with Cat G and solve its structure by X-ray crystallography (3.5 A). Structural details from the X-ray analysis of 1.Cat G served as a platform for optimization of this lead compound by structure-based drug design. With the aid of molecular modeling, substituents were attached to the 3-position of the 2-naphthyl ring of 1, which occupies the S1 pocket of Cat G, to provide an extension into the hydrophobic S3 region. Thus, we arrived at analogue 7 with an 80-fold potency improvement over 1 (IC(50) = 53 nM). From these results, it is evident that the beta-ketophosphonic acid unit can form the basis for a novel class of serine protease inhibitors.

  DOI：

  10.1021/ja017506h
• 作为产物：
  描述：

  2，3-萘二酐 、 1-萘基甲基膦酸二乙酯 生成 3-(2-(二乙氧基磷酰基)-2-(萘-1-基)乙酰基)-2-萘甲酸
  参考文献：
  名称：

  Novel phosphonic acid compounds as inhibitors of serine proteases

  摘要：

  本发明涉及磷酸化合物，可用作丝氨酸蛋白酶抑制剂，以及其组成物和治疗炎症和丝氨酸蛋白酶介导的疾病的方法。

  公开号：

  US20030195172A1
• 作为试剂：
  描述：

  3-(2-(二乙氧基磷酰基)-2-(萘-1-基)乙酰基)-2-萘甲酸 、 [4-(Methylamino)piperidin-1-yl]-naphthalen-2-ylmethanone 在 3-(2-(二乙氧基磷酰基)-2-(萘-1-基)乙酰基)-2-萘甲酸 作用下， 生成 3-(2-diethoxyphosphoryl-2-naphthalen-1-ylacetyl)-N-methyl-N-[1-(naphthalene-2-carbonyl)piperidin-4-yl]naphthalene-2-carboxamide
  参考文献：
  名称：

  Novel phosphonic acid compounds as inhibitors of serine proteases

  摘要：

  本发明涉及磷酸化合物，可用作丝氨酸蛋白酶抑制剂，以及其组成物和治疗炎症和丝氨酸蛋白酶介导的疾病的方法。

  公开号：

  US20030195172A1

文献信息

• [EN] PHOSPHONIC ACID COMPOUNDS AS INHIBITORS OF SERINE PROTEASES<br/>[FR] COMPOSES D'ACIDE PHOSPHONIQUE UTILISES COMME INHIBITEURS DE SERINE PROTEASES
  申请人：ORTHO MCNEIL PHARM INC

  公开号：WO2003035654A1

  公开（公告）日：2003-05-01

  The present invention is directed to phosphonic acid compounds useful as serine protease inhibitors, compositions thereof and methods for treating inflammatory and serine protease mediated disorders.

  本发明涉及磷酸类化合物，其作为丝氨酸蛋白酶抑制剂有用，以及其组成物和用于治疗炎症和丝氨酸蛋白酶介导的疾病的方法。
• PIPERAZINE CONTAINING PHOSPHONIC ACID COMPOUNDS AS INHIBITORS OF SERINE PROTEASES
  申请人：Ortho-Mcneil Pharmaceutical Corp.

  公开号：EP1620446B1

  公开（公告）日：2012-10-24
• NOVEL PHOSPHONIC ACID COMPOUNDS AS INHIBITORS OF SERINE PROTEASES
  申请人：Greco Michael N.

  公开号：US20110086819A1

  公开（公告）日：2011-04-14

  The present invention is directed to phosphonic acid compounds useful as serine protease inhibitors, compositions thereof and methods for treating inflammatory and serine protease mediated disorders.
• US7459461B2
  申请人：——

  公开号：US7459461B2

  公开（公告）日：2008-12-02
• US8178673B2
  申请人：——

  公开号：US8178673B2

  公开（公告）日：2012-05-15