(6R)-6-(5-chloro-2-methoxybenzyl)-1-(2,4,6-trimethoxybenzyl)-1,4-diazepan-2,5-dione | 889857-40-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (6R)-6-(5-chloro-2-methoxybenzyl)-1-(2,4,6-trimethoxybenzyl)-1,4-diazepan-2,5-dione
• 英文别名: (6R)-(5-chloro-2-methoxybenzyl)-1-(2,4,6-trimethoxybenzyl)-1,4-diazepan-2,5-dione；(6R)-6-(5-chloro-2-methoxybenzyl)-1-(2,4,6-trimethoxybenzyl)-1,4-diazepane-2,5-dione；(6R)-6-[(5-chloro-2-methoxyphenyl)methyl]-1-[(2,4,6-trimethoxyphenyl)methyl]-1,4-diazepane-2,5-dione
• CAS: 889857-40-3
• 化学式: C₂₃H₂₇ClN₂O₆
• 分子量: 462.93
• InChiKey: UHWOJUCYDDAZDX-OAHLLOKOSA-N

物化性质

• 沸点：
  692.3±55.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (6R)-6-(5-chloro-2-methoxybenzyl)-1-(2,4,6-trimethoxybenzyl)-1,4-diazepan-2,5-dione 在 盐酸 、 4-二甲氨基吡啶 、 正丁基锂 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.33h， 生成 2-amino-4-[(1R)-1-({[(6R)-6-(5-chloro-2-methoxybenzyl)-3,7-dioxo-1,4-diazepan-1-yl]carbonyl}amino)propyl]benzoic acid
  参考文献：
  名称：

  Development of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5-diones as orally active human chymase inhibitors

  摘要：

  A novel series of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5-diones was designed, synthesized, and evaluated as human chymase inhibitors. From this series, we identified several compounds which were effective, via oral administration, in a mouse model of chronic dermatitis. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.085
• 作为产物：
  描述：

  5-氯-2-甲氧基苯甲醛 在 吡啶 、 三乙烯二胺 、 盐酸 、 sodium azide 、 2 % platinum on carbon 、 水 、 氢气 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 二乙醇胺 、 三苯基膦 、 sodium hydroxide 、 lanthanum(lll) triflate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 、 三氟乙酸 为溶剂， 反应 147.16h， 生成 (6R)-6-(5-chloro-2-methoxybenzyl)-1-(2,4,6-trimethoxybenzyl)-1,4-diazepan-2,5-dione
  参考文献：
  名称：

  Discovery of novel series of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5-diones as human chymase inhibitors using structure-based drug design

  摘要：

  A novel series of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5-diones were explored as human chymase inhibitors using structure-based drug design according to the X-ray cocrystal structure of chymase and compound 1. The optimization focused on the prime site led to the attainment of compounds that showed potent inhibitory activity, and among them, 18R shows a novel interaction mode. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.079

文献信息

• SEVEN-MEMBERED RING COMPOUND AND PHARMACEUTICAL USE THEREFOR
  申请人：Muto Tsuyoshi

  公开号：US20120259111A1

  公开（公告）日：2012-10-11

  A compound having a 7-membered nitrogen-containing ring skeleton represented by the formula (I), which is useful for the prevention or treatment of diseases, in which chymase is involved and a pharmaceutical containing the same for the prevention or treatment of a disease, in which chymase is involved.

  一种具有由式(I)表示的含氮七元环骨架的化合物，对涉及chymase的疾病的预防或治疗有用，以及含有该化合物的药物，用于预防或治疗涉及chymase的疾病。
• Discovery and structure–activity relationship study of 1,3,6-trisubstituted 1,4-diazepane-7-ones as novel human kallikrein 7 inhibitors
  作者：Hidenobu Murafuji、Hiroki Sakai、Megumi Goto、Seiichi Imajo、Hajime Sugawara、Tsuyoshi Muto

  DOI：10.1016/j.bmcl.2017.10.030

  日期：2017.12

  discovered as a novel human kallikrein 7 (KLK7, stratum corneum chymotryptic enzyme, SCCE) inhibitor, and its derivatives were synthesized and evaluated. Structure–activity relationship studies of the amidoxime unit and benzoic acid part of this new scaffold led to the identification of 25 and 34, which were more potent than the hit compound, 1. The X-ray co-crystal structure of compound 25 and human KLK7

  发现了由1,3,6-三取代的1,4-二氮杂-7-one组成的化合物1作为新型人激肽释放酶7（KLK7，角质层糜蛋白酶，SCCE）抑制剂，并对其衍生物进行合成和评估。对这种新型支架的mid胺肟单元和苯甲酸部分的结构-活性关系的研究导致鉴定出25和34，它们比命中化合物1更有效。化合物25和人KLK7的X射线共晶体结构揭示了特征相互作用，并能解释结构与活性之间的关系。
• Structure-based drug design of 1,3,6-trisubstituted 1,4-diazepan-7-ones as selective human kallikrein 7 inhibitors
  作者：Hidenobu Murafuji、Hiroki Sakai、Megumi Goto、Yoshiaki Oyama、Seiichi Imajo、Hajime Sugawara、Toshiyuki Tomoo、Tsuyoshi Muto

  DOI：10.1016/j.bmcl.2018.03.011

  日期：2018.5

  enzyme) inhibitors. Based on the X-ray co-crystal structure of compound 1 bound to human KLK7, the derivatives of this scaffold were designed, synthesized, and evaluated. Through structure-activity relationship studies focused on the side chain located in the prime site region of the enzyme, representative compounds 15, 33a, and 35a were identified as highly potent and selective inhibitors of human

  研究了一系列新的1,3,6-三取代的1,4-二氮杂-7-酮类化合物，作为人激肽释放酶7（KLK7，角质层胰凝乳蛋白酶）抑制剂。根据与人KLK7结合的化合物1的X射线共晶体结构，设计，合成和评估该支架的衍生物。通过结构-活性关系研究集中在位于所述酶的主要位点区域中的侧链，代表性的化合物15，33A，和35A被鉴定为人类KLK7的高度有效的和选择性的抑制剂。
• 7-MEMBERED RING COMPOUND AND METHOD OF PRODUCTION AND PHARMACEUTICAL APPLICATION THEREOF
  申请人：Muto Tsuyoshi

  公开号：US20090253683A1

  公开（公告）日：2009-10-08

  A 7-membered heterocyclic compound having the formula (I), or its salt, or a solvate thereof with a chymase inhibitory action and useful for the prevention or treatment of various diseases, in which chymase is involved: a method for producing the same, and a pharmaceutical composition useful for the prevention or treatment of diseases, in which chymase is involved, including the compound of having the formula (I), or its pharmaceutically acceptable salt, or a solvate thereof are provided.

  本发明提供一种具有式(I)的7元杂环化合物或其盐或其溶剂合物，具有抑制chymase的作用，用于预防或治疗各种涉及chymase的疾病的方法，以及用于预防或治疗各种涉及chymase的疾病的药物组合物，包括具有式(I)的化合物或其药学上可接受的盐或其溶剂合物的药物组合物。
• 7-membered ring compound and method of production and pharmaceutical application thereof
  申请人：Muto Tsuyoshi

  公开号：US20090111796A1

  公开（公告）日：2009-04-30

  A 7-membered heterocyclic compound having the formula (I), or its salt, or a solvate thereof with a chymase inhibitory action and useful for the prevention or treatment of various diseases, in which chymase is involved: a method for producing the same, and a pharmaceutical composition useful for the prevention or treatment of diseases, in which chymase is involved, including the compound of having the formula (I), or its pharmaceutically acceptable salt, or a solvate thereof are provided.

  提供了一种具有以下公式（I）或其盐或溶剂化物的七元杂环化合物，具有抑制chymase作用，可用于预防或治疗各种涉及chymase的疾病的方法，以及用于预防或治疗这些疾病的制药组合物，包括具有以下公式（I）或其药学上可接受的盐或溶剂化物的化合物。