N-[3-(3-cyanophenyl)-1-oxo-1-(4-phenylpiperazin-1-yl)propan-2-yl]naphthalene-2-sulfonamide | 144797-96-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-[3-(3-cyanophenyl)-1-oxo-1-(4-phenylpiperazin-1-yl)propan-2-yl]naphthalene-2-sulfonamide
• CAS: 144797-96-6
• 化学式: C₃₀H₂₈N₄O₃S
• 分子量: 524.643
• InChiKey: TZPPTNRGYFYMTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[3-(3-cyanophenyl)-1-oxo-1-(4-phenylpiperazin-1-yl)propan-2-yl]naphthalene-2-sulfonamide 在 盐酸 、 氨 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 100.0h， 生成 3-[2-(Naphthalene-2-sulfonylamino)-3-oxo-3-(4-phenyl-piperazin-1-yl)-propyl]-benzamidine
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Potent Thrombin Inhibitors:  Piperazides of 3-Amidinophenylalanine

  摘要：

  Thrombin is the key enzyme in the blood coagulation system, and inhibitors of its proteolytic activity are of therapeutic interest since they are potential anticoagulants. The most potent inhibitor of the benzamidine type is N-alpha-[(2-naphthylsulfonyl)glycyl]-4-amidinophenylalanylpiperidide (NAPAP). However, NAPAP and other benzamidine derivatives do not show favorable pharmacological properties; above all, they have very low systemic bioavailability after oral administration. The goal of designing new compounds was to obtain potent inhibitors with improved pharmacokinetic properties. Piperazide derivatives of 3-amidinophenylalanine as the key building block were synthesized. The piperazine moiety opened the possibility to introduce quite different substituents on the second nitrogen using common synthetic procedures. Some of the newly synthesized compounds are potent inhibitors of thrombin and offer an approach to study structure-function relationships for inhibition of thrombin and related enzymes and for the improvement of their pharmacokinetic properties.

  DOI：

  10.1021/jm960668h
• 作为产物：
  描述：

  3-cyano-DL-phenylalanine methyl ester hydrochloride 在 N-甲基吗啉 、 盐酸 、 氯化亚砜 、 溶剂黄146 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙酸乙酯 为溶剂， 反应 20.0h， 生成 N-[3-(3-cyanophenyl)-1-oxo-1-(4-phenylpiperazin-1-yl)propan-2-yl]naphthalene-2-sulfonamide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Potent Thrombin Inhibitors:  Piperazides of 3-Amidinophenylalanine

  摘要：

  Thrombin is the key enzyme in the blood coagulation system, and inhibitors of its proteolytic activity are of therapeutic interest since they are potential anticoagulants. The most potent inhibitor of the benzamidine type is N-alpha-[(2-naphthylsulfonyl)glycyl]-4-amidinophenylalanylpiperidide (NAPAP). However, NAPAP and other benzamidine derivatives do not show favorable pharmacological properties; above all, they have very low systemic bioavailability after oral administration. The goal of designing new compounds was to obtain potent inhibitors with improved pharmacokinetic properties. Piperazide derivatives of 3-amidinophenylalanine as the key building block were synthesized. The piperazine moiety opened the possibility to introduce quite different substituents on the second nitrogen using common synthetic procedures. Some of the newly synthesized compounds are potent inhibitors of thrombin and offer an approach to study structure-function relationships for inhibition of thrombin and related enzymes and for the improvement of their pharmacokinetic properties.

  DOI：

  10.1021/jm960668h

文献信息

• [EN] INHIBITORS OF GROWTH FACTOR ACTIVATION ENZYMES<br/>[FR] INHIBITEURS D'ENZYMES D'ACTIVATION DE FACTEUR DE CROISSANCE
  申请人：UNIV WASHINGTON

  公开号：WO2016144654A1

  公开（公告）日：2016-09-15

  The present invention generally relates to compounds that are useful for inhibiting one or more of hepatocyte growth factor activator, matriptase, hepsin, Factor Xa, or thrombin. The present invention also relates to various methods of using the inhibitor compounds including treating a malignancy, a pre-malignant condition, or cancer by administering an effective amount of the inhibitor to a subject in need thereof.

  本发明通常涉及对抑制肝细胞生长因子激活剂、麦曲丝蛋白、赫普星、Xa因子或凝血酶等的化合物有用的化合物。本发明还涉及使用抑制剂化合物的各种方法，包括通过向需要的受试者施用有效量的抑制剂来治疗恶性肿瘤、癌前病变或癌症。
• Inhibitors of growth factor activation enzymes
  申请人：Janetka James W.

  公开号：US11130780B2

  公开（公告）日：2021-09-28

  The present invention generally relates to compounds that are useful for inhibiting one or more of hepatocyte growth factor activator, matriptase, hepsin, Factor Xa, or thrombin. The present invention also relates to various methods of using the inhibitor compounds including treating a malignancy, a pre-malignant condition, or cancer by administering an effective amount of the inhibitor to a subject in need thereof.

  本发明一般涉及可用于抑制一种或多种肝细胞生长因子激活剂、淀粉酶、肝素、Xa因子或凝血酶的化合物。 本发明还涉及使用抑制剂化合物的各种方法，包括通过向有需要的受试者施用有效量的抑制剂来治疗恶性肿瘤、恶性肿瘤前期病症或癌症。
• INHIBITORS OF GROWTH FACTOR ACTIVATION ENZYMES
  申请人：Janetka James W.

  公开号：US20180066015A1

  公开（公告）日：2018-03-08

  The present invention generally relates to compounds that are useful for inhibiting one or more of hepatocyte growth factor activator, matriptase, hepsin, Factor Xa, or thrombin. The present invention also relates to various methods of using the inhibitor compounds including treating a malignancy, a pre-malignant condition, or cancer by administering an effective amount of the inhibitor to a subject in need thereof.
• Synthesis and Structure−Activity Relationships of Potent Thrombin Inhibitors:  Piperazides of 3-Amidinophenylalanine
  作者：Jörg Stürzebecher、Dagmar Prasa、Jörg Hauptmann、Helmut Vieweg、Peter Wikström

  DOI：10.1021/jm960668h

  日期：1997.9.1

  Thrombin is the key enzyme in the blood coagulation system, and inhibitors of its proteolytic activity are of therapeutic interest since they are potential anticoagulants. The most potent inhibitor of the benzamidine type is N-alpha-[(2-naphthylsulfonyl)glycyl]-4-amidinophenylalanylpiperidide (NAPAP). However, NAPAP and other benzamidine derivatives do not show favorable pharmacological properties; above all, they have very low systemic bioavailability after oral administration. The goal of designing new compounds was to obtain potent inhibitors with improved pharmacokinetic properties. Piperazide derivatives of 3-amidinophenylalanine as the key building block were synthesized. The piperazine moiety opened the possibility to introduce quite different substituents on the second nitrogen using common synthetic procedures. Some of the newly synthesized compounds are potent inhibitors of thrombin and offer an approach to study structure-function relationships for inhibition of thrombin and related enzymes and for the improvement of their pharmacokinetic properties.