Boc-Lys(Cbz)-(2-thiazolyl) | 190903-90-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Boc-Lys(Cbz)-(2-thiazolyl)
• 英文别名: tert-butyl-N-[(1S)-5-(benzyloxycarbonylamino)-1-(thiazole-2-carbonyl)pentyl]carbamate；benzyl N-[(5S)-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-oxo-6-(1,3-thiazol-2-yl)hexyl]carbamate
• CAS: 190903-90-3
• 化学式: C₂₂H₂₉N₃O₅S
• 分子量: 447.555
• InChiKey: GZDHAUAFZALQLY-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Boc-Lys(Cbz)-(2-thiazolyl) 在 盐酸 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 21.0h， 生成 benzyl-N-[(5S)-5-(cyclopentanecarbonylamino)-6-oxo-6-thiazol-2-yl-hexyl]carbamate
  参考文献：
  名称：

  INHIBITORS OF LYSINE GINGIPAIN

  摘要：

  本发明通常涉及针对细菌牙龈脓红素Porphyromonas gingivalis及其蛋白酶赖氨酸龈蛋白酶（Kgp）的治疗方法，以及它们用于治疗与P. gingivalis感染相关的疾病，包括脑部疾病如阿尔茨海默病。在某些实施例中，本发明提供根据本文所述的I式化合物及其药用可接受的盐。

  公开号：

  US20160096830A1
• 作为产物：
  描述：

  Nalpha-BOC-Nepsilon-CBZ-L-赖氨酸 DCHA 在 正丁基锂 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 Boc-Lys(Cbz)-(2-thiazolyl)
  参考文献：
  名称：

  Unique Overlap in the Prerequisites for Thrombin Inhibition and Oral Bioavailability Resulting in Potent Oral Antithrombotics

  摘要：

  Despite intense research over the last 10 years, aided by the availability of X-ray structures of enzyme-inhibitor complexes, only very few truly orally active thrombin inhibitors have been found. We conducted a comprehensive study starting with peptide transition state analogues (TSA). Both hydrophobic nonpeptide analogues as well as hydrophilic peptidic analogues were synthesized. The bioavailability in rats and dogs could be drastically altered depending on the overall charge distribution in the molecule. Compound 27, a tripeptide TSA inhibitor of thrombin, showed an oral bioavailability of 32% in rats and 71% in dogs, elimination half-lives being 58 and 108 min, respectively. The thrombin inhibition constant of compound 27 was 1.1 nM, and in an in vivo arterial flow model, the ED50 was 5.4 nmol/kg(.)min, comparable to known non-TSA inhibitors. A molecular design was found that combines antithrombotic efficiency with oral bioavailability at low dosages.

  DOI：

  10.1021/jm011110z

文献信息

• Inhibitors of lysine gingipain
  申请人：Cortexyme, Inc.

  公开号：US10301301B2

  公开（公告）日：2019-05-28

  The present invention relates generally to therapeutics targeting the bacterium Porphyromonas gingivalis, including its protease Lysine gingipain (Kgp), and their use for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimer's disease. In certain embodiments, the invention provides compounds according to Formula I, as described herein, and pharmaceutically acceptable salts thereof.

  本发明一般涉及针对牙龈卟啉单胞菌（包括其蛋白酶赖氨酸龈肽酶（Kgp））的治疗药物，及其用于治疗与牙龈卟啉单胞菌感染相关的疾病，包括脑部疾病，如阿尔茨海默氏症。在某些实施方案中，本发明提供了本文所述的根据式 I 的化合物及其药学上可接受的盐。
• US9758473B2
  申请人：——

  公开号：US9758473B2

  公开（公告）日：2017-09-12
• US9988375B2
  申请人：——

  公开号：US9988375B2

  公开（公告）日：2018-06-05
• INHIBITORS OF LYSINE GINGIPAIN
  申请人：Cortexyme, Inc.

  公开号：US20160096830A1

  公开（公告）日：2016-04-07

  The present invention relates generally to therapeutics targeting the bacterium Porphyromonas gingivalis , including its protease Lysine gingipain (Kgp), and their use for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimer's disease. In certain embodiments, the invention provides compounds according to Formula I, as described herein, and pharmaceutically acceptable salts thereof.

  本发明通常涉及针对细菌牙龈脓红素Porphyromonas gingivalis及其蛋白酶赖氨酸龈蛋白酶（Kgp）的治疗方法，以及它们用于治疗与P. gingivalis感染相关的疾病，包括脑部疾病如阿尔茨海默病。在某些实施例中，本发明提供根据本文所述的I式化合物及其药用可接受的盐。
• Unique Overlap in the Prerequisites for Thrombin Inhibition and Oral Bioavailability Resulting in Potent Oral Antithrombotics
  作者：Anton E. P. Adang、Adrianus P. A. de Man、Gerard M. T. Vogel、Peter D. J. Grootenhuis、Martin J. Smit、Co A. M. Peters、Arie Visser、Jos B. M. Rewinkel、Theo van Dinther、Hans Lucas、Jan Kelder、Sjoerd van Aelst、Dick G. Meuleman、Constant A. A. van Boeckel

  DOI：10.1021/jm011110z

  日期：2002.9.1

  Despite intense research over the last 10 years, aided by the availability of X-ray structures of enzyme-inhibitor complexes, only very few truly orally active thrombin inhibitors have been found. We conducted a comprehensive study starting with peptide transition state analogues (TSA). Both hydrophobic nonpeptide analogues as well as hydrophilic peptidic analogues were synthesized. The bioavailability in rats and dogs could be drastically altered depending on the overall charge distribution in the molecule. Compound 27, a tripeptide TSA inhibitor of thrombin, showed an oral bioavailability of 32% in rats and 71% in dogs, elimination half-lives being 58 and 108 min, respectively. The thrombin inhibition constant of compound 27 was 1.1 nM, and in an in vivo arterial flow model, the ED50 was 5.4 nmol/kg(.)min, comparable to known non-TSA inhibitors. A molecular design was found that combines antithrombotic efficiency with oral bioavailability at low dosages.