组织蛋白酶G抑制剂 | 429676-93-7

• 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: 组织蛋白酶G抑制剂
• 英文名称: cathepsin G inhibitor I
• 英文别名: [2-[3-[(1-benzoylpiperidin-4-yl)-methylcarbamoyl]naphthalen-2-yl]-1-naphthalen-1-yl-2-oxoethyl]phosphonic acid
• CAS: 429676-93-7
• 化学式: C₃₆H₃₃N₂O₆P
• 分子量: 620.642
• InChiKey: GNOZQRKYZJSIPZ-UHFFFAOYSA-N

物化性质

• 沸点：
  912.0±75.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  45
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-叔丁氧羰基氨基哌啶 在 吡啶 、 三甲基溴硅烷 、 potassium hydride 、 1-羟基苯并三唑 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 84.75h， 生成 组织蛋白酶G抑制剂
  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

文献信息

• Novel phosphonic acid compounds as inhibitors of serine proteases
  申请人：——

  公开号：US20030195172A1

  公开（公告）日：2003-10-16

  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.

  本发明涉及磷酸化合物，可用作丝氨酸蛋白酶抑制剂，以及这些化合物的组合物和治疗炎症和丝氨酸蛋白酶介导的疾病的方法。
• [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。
• Cancer diagnosis and therapy
  申请人：GILLIES MCINDOE RESEARCH INSTITUTE

  公开号：US10281472B2

  公开（公告）日：2019-05-07

  The present invention provides a novel approach to cancer diagnosis and therapy of cancer by providing compositions and methods for the identification and specific targeting of the cancer stem cell populations present in a tumor to eradicate, or slow or prevent tumor (5) growth and spread, including the potential for tumor metastasis, by modulation of the Renin-Angiotensin System including, but not limited to, Renin Receptor, Angiotensin II Receptor (2) and a secreted form of the Renin Receptor.

  本发明为癌症诊断和治疗提供了一种新方法，通过调节肾素-血管紧张素系统（包括但不限于肾素受体、血管紧张素 II 受体 (2) 和肾素受体的分泌形式），提供用于识别和特异性靶向肿瘤中存在的癌症干细胞群的组合物和方法，以根除或减缓或预防肿瘤 (5) 的生长和扩散，包括肿瘤转移的可能性。
• PHOSPHONIC ACID COMPOUNDS AS INHIBITORS OF SERINE PROTEASES
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1438316B1

  公开（公告）日：2006-06-21
• CANCER DIAGNOSIS AND THERAPY
  申请人：Gillies Mcindoe Research Institute

  公开号：EP3180000A1

  公开（公告）日：2017-06-21