N-[2-(3,4-dimethoxyphenyl)acetyl]-N'-(tert-butyloxycarbonyl)guanidine

• 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: N-[2-(3,4-dimethoxyphenyl)acetyl]-N'-(tert-butyloxycarbonyl)guanidine
• 英文别名: tert-butyl N-[N-[2-(3,4-dimethoxyphenyl)acetyl]carbamimidoyl]carbamate
• 化学式: C₁₆H₂₃N₃O₅
• 分子量: 337.376
• InChiKey: IALFJXCQZSQTGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[2-(3,4-dimethoxyphenyl)acetyl]-N'-(tert-butyloxycarbonyl)guanidine 在 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Structure-based optimization of non-peptidic Cathepsin D inhibitors

  摘要：

  We discovered a novel series of non-peptidic acylguanidine inhibitors of Cathepsin D as target for osteoarthritis. The initial HTS-hits were optimized by structure-based design using CatD X-ray structures resulting in single digit nanomolar potency in the biochemical CatD assay. However, the most potent analogues showed only micromolar activities in an ex vivo glycosaminoglycan (GAG) release assay in bovine cartilage together with low cellular permeability and suboptimal microsomal stability. This new scaffold can serve as a starting point for further optimization towards in vivo efficacy. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.07.054
• 作为产物：
  描述：

  3,4-二甲氧基苯乙酸 在 草酰氯 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-[2-(3,4-dimethoxyphenyl)acetyl]-N'-(tert-butyloxycarbonyl)guanidine
  参考文献：
  名称：

  Structure-based optimization of non-peptidic Cathepsin D inhibitors

  摘要：

  We discovered a novel series of non-peptidic acylguanidine inhibitors of Cathepsin D as target for osteoarthritis. The initial HTS-hits were optimized by structure-based design using CatD X-ray structures resulting in single digit nanomolar potency in the biochemical CatD assay. However, the most potent analogues showed only micromolar activities in an ex vivo glycosaminoglycan (GAG) release assay in bovine cartilage together with low cellular permeability and suboptimal microsomal stability. This new scaffold can serve as a starting point for further optimization towards in vivo efficacy. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.07.054

文献信息

• ACYLGUANIDINES FOR TREATING OSTEOARTHRITIS
  申请人：MERCK PATENT GMBH

  公开号：US20150361037A1

  公开（公告）日：2015-12-17

  The present invention relates to compounds of the formula (I) and in particular to medicaments comprising at least one compound of the formula I for use in the treatment and/or prophylaxis of physiological and/or pathophysiological conditions in the triggering of which cathepsin D is involved, in particular for use in the treatment and/or prophylaxis of osteoarthritis, traumatic cartilage injuries, arthritis, pain, allodynia or hyperalgesia.

  本发明涉及公式（I）的化合物，特别是涉及至少一种公式I化合物构成的药物，用于治疗和/或预防在其中天冬氨酸蛋白酶D参与的生理和/或病理生理状况，特别是用于治疗和/或预防骨关节炎、创伤性软骨损伤、关节炎、疼痛、触痛或过敏性疼痛。
• [EN] COMPOUNDS AND METHODS FOR THE TREATMENT OF NON‑ALCOHOLIC STEATOHEPATITIS<br/>[FR] COMPOSÉS ET PROCÉDÉS DESTINÉS AU TRAITEMENT DE LA STÉATOHÉPATITE NON ALCOOLIQUE
  申请人：AVALIV THERAPEUTICS

  公开号：WO2019111225A1

  公开（公告）日：2019-06-13

  Compounds and compositions are provided having the structure of Formula (I) or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein T, T', U, U', V, W, R1, R2, R3', n, o, o', o'', and o''' are as defined herein. Such compounds are useful for treating liver diseases and abnormal liver conditions, including non-alcoholic steatohepatitis via inhibition of the lysosomal enzyme cathepsin D. Accordingly, a variety of treatment methods are hereby disclosed, including treatment of underlying conditions such as hepatic inflammation, aberrant lipid metabolism, and irregular lysosomal function.

  提供具有Formula (I)结构或其药用可接受的盐、互变异构体或立体异构体的化合物和组合物，其中T、T'、U、U'、V、W、R1、R2、R3'、n、o、o'、o''和o'''如本文所定义。这些化合物可用于治疗肝病和异常肝脏状况，包括通过抑制溶酶体酶蛋白酶D来治疗非酒精性脂肪性肝炎。因此，这里公开了各种治疗方法，包括治疗基础疾病，如肝脏炎症、异常脂质代谢和溶酶体功能异常。
• ACYLGUANIDINE ZUR BEHANDLUNG VON ARTHROSE
  申请人：Merck Patent GmbH

  公开号：EP2945929A1

  公开（公告）日：2015-11-25
• US7255835B2
  申请人：——

  公开号：US7255835B2

  公开（公告）日：2007-08-14
• US9884814B2
  申请人：——

  公开号：US9884814B2

  公开（公告）日：2018-02-06