4-(Aminomethyl)-N,N'-bis[(1,1-dimethylethoxy)carbonyl]-1-piperidinecarboximidamide | 162167-83-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(Aminomethyl)-N,N'-bis[(1,1-dimethylethoxy)carbonyl]-1-piperidinecarboximidamide
• 英文别名: tert-butyl (NE)-N-[[4-(aminomethyl)piperidin-1-yl]-[(2-methylpropan-2-yl)oxycarbonylamino]methylidene]carbamate
• CAS: 162167-83-1
• 化学式: C₁₇H₃₂N₄O₄
• 分子量: 356.465
• InChiKey: YKLXVBGYFUGEMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(Aminomethyl)-N,N'-bis[(1,1-dimethylethoxy)carbonyl]-1-piperidinecarboximidamide 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-[[1-(Aminoiminomethyl)-4-piperidinyl]methyl]-1-D-phenylalanyl-L-prolinamide
  参考文献：
  名称：

  Molecular design and structure–Activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664

  摘要：

  A series of structurally novel small molecule inhibitors of human alpha -thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha -thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00667-9
• 作为产物：
  描述：

  N-[苯基亚甲基]-1-(哌啶-4-基)甲胺 在 potassium hydrogensulfate 作用下， 生成 4-(Aminomethyl)-N,N'-bis[(1,1-dimethylethoxy)carbonyl]-1-piperidinecarboximidamide
  参考文献：
  名称：

  Molecular design and structure–Activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664

  摘要：

  A series of structurally novel small molecule inhibitors of human alpha -thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha -thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00667-9

文献信息

• Heterocyclic thrombin inhibitors
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP0648780A1

  公开（公告）日：1995-04-19

  Heterocyclic thrombin inhibitors are provided which have the structure including all stereoisomers thereof wherein n is 0, l or 2;    p is 0, l or 2;    Q is a single bond or C=O;    A is aryl or cycloalkyl, or an azacycloalkyl ring or an azaheteroalkyl ring;    R⁵ is guanidine, amidine or aminomethyl, but when A is azacycloalkyl or azaheteroalkyl, R⁵ is amidine;    R¹ and R² are independently hydrogen, lower alkyl, cycloalkyl, aryl, hydroxy alkoxy, keto, thioketal, thioalkyl, thioaryl, amino or alkylamino; or R¹ and R² together with the carbons to which they are attached form a cycloalkyl aryl, or heteroaryl ring;    R⁴ is hydrogen, hydroxyalkyl, aminoalkyl, amidoalkyl, alkyl, cycloalkyl, aryl, arylalkyl, alkenyl, alkynyl, arylalkoxyalkyl, or an amino acid side chain, either protected or unprotected; and    R³ is hydrogen, or -CO₂R⁶ (wherein R⁶ is lower alkyl, aryl, arylalkyl or cycloheteroalkyl);    including pharmaceutically acceptable salts thereof.

  所提供的杂环凝血酶抑制剂具有以下结构 包括其所有立体异构体 其中 n 为 0、l 或 2； p为0、l或2 Q 是单键或 C=O； A 是芳基或环烷基，或偶氮环烷基环或偶氮杂烷基环； R⁵ 是胍基、脒基或氨甲基，但当 A 是偶氮环烷基或杂杂环烷基时，R⁵ 是脒基； R¹ 和 R² 独立地是氢、低级烷基、环烷基、芳基、羟基烷氧基、酮基、硫酮基、硫代烷基、硫代芳基、氨基或烷基氨基；或 R¹ 和 R² 与它们所连接的碳一起形成环烷基芳基或杂芳基环； R⁴ 是氢、羟烷基、氨基烷基、氨基烷基、烷基、环烷基、芳基、芳烷基、烯基、炔基、芳基烷氧基烷基或氨基酸侧链，可以是受保护的，也可以是未受保护的；以及 R³ 为氢、 或-CO₂R⁶（其中 R⁶ 是低级烷基、芳基、芳烷基或环杂烷基）； 包括其药学上可接受的盐类。
• Substrate-based peptidomimetic inhibitors of the Murray Valley encephalitis virus NS2B/NS3 serine protease: A P1–P4 SAR study
  作者：Melgious Jin Yan Ang、Gerald Han Jie Yong、Anders Poulsen、Siew Wen Then、Zhitao Li、Joma Joy、Jeffrey Hill、Cheng San Brian Chia

  DOI：10.1016/j.ejmech.2013.07.028

  日期：2013.10

  Murray Valley encephalitis is an infectious disease spread by a mosquito-borne virus endemic in Papua New Guinea and northern Australia. In the past decade, it has spread to various regions of Australia and there is currently no therapeutic treatment against this disease. An attractive drug target is the viral serine protease NS2B/NS3, a critical enzyme involved in viral replication. Herein, we report the inhibitory activities of 37 C-terminal agmatine peptidomimetic inhibitors which led to the design of a novel structurally-constrained competitive inhibitor 38 possessing a K-i of 2.5 +/- 0.5 mu M. We believe our data provides crucial insights into the viral protease active site specificity which could be used to facilitate drug design against Murray Valley encephalitis viral infections. (C) 2013 Elsevier Masson SAS. All rights reserved.
• DIAMIDE MACROCYCLES THAT ARE FXIA INHIBITORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20170283403A1

  公开（公告）日：2017-10-05

  The present invention provides compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective Factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.
• US5583146A
  申请人：——

  公开号：US5583146A

  公开（公告）日：1996-12-10
• [EN] DIAMIDE MACROCYCLES THAT ARE FXIA INHIBITORS<br/>[FR] DIAMIDES MACROCYCLIQUES QUI SONT DES INHIBITEURS DE FXIA
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2016036893A1

  公开（公告）日：2016-03-10

  The present invention provides compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective Factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.