(S)-2-[(3S,5R)-3-isobutyl-5-methyl-2-oxo-[1,4]diazepan-1-yl]-3-(naphthalen-2-yl)-propionamide | 334941-80-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-2-[(3S,5R)-3-isobutyl-5-methyl-2-oxo-[1,4]diazepan-1-yl]-3-(naphthalen-2-yl)-propionamide
• 英文别名: (2S)-2-[(3S,5R)-5-methyl-3-(2-methylpropyl)-2-oxo-1,4-diazepan-1-yl]-3-naphthalen-2-ylpropanamide
• CAS: 334941-80-9
• 化学式: C₂₃H₃₁N₃O₂
• 分子量: 381.518
• InChiKey: GQHBCZHZVSUIQZ-CZAAIQMYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  吡啶-4-乙酸 、 (S)-2-[(3S,5R)-3-isobutyl-5-methyl-2-oxo-[1,4]diazepan-1-yl]-3-(naphthalen-2-yl)-propionamide 在 二氯乙基铝 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 (S)-2-[(3S,5R)-3-Isobutyl-5-methyl-2-oxo-4-(2-pyridin-4-yl-acetyl)-[1,4]diazepan-1-yl]-3-naphthalen-2-yl-propionamide
  参考文献：
  名称：

  1,4-Diazepane-2-ones as novel inhibitors of LFA-1

  摘要：

  The design, synthesis, and biological evaluation of 1,4-diazepane-2-ones as novel LFA-1 antagonists from a scaffold-based combinatorial library are described. Initial optimization of the library lead has resulted in high-affinity antagonists of the LFA-1/ICAM-1 interaction, such as compounds 18d and 18e with IC50 values of 110 and 70 nM, respectively. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00991-5
• 作为产物：
  描述：

  H-2-Nal-NH2 hydrochloride 在 N-甲基吗啉 、 碳酸二异丙酯 、 sodium cyanoborohydride 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.75h， 生成 (S)-2-[(3S,5R)-3-isobutyl-5-methyl-2-oxo-[1,4]diazepan-1-yl]-3-(naphthalen-2-yl)-propionamide
  参考文献：
  名称：

  1,4-Diazepane-2-ones as novel inhibitors of LFA-1

  摘要：

  The design, synthesis, and biological evaluation of 1,4-diazepane-2-ones as novel LFA-1 antagonists from a scaffold-based combinatorial library are described. Initial optimization of the library lead has resulted in high-affinity antagonists of the LFA-1/ICAM-1 interaction, such as compounds 18d and 18e with IC50 values of 110 and 70 nM, respectively. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00991-5

文献信息

• Substituted 2-oxo-1,4-diazacycloalkanes
  申请人：Novartis AG

  公开号：US06399599B1

  公开（公告）日：2002-06-04

  Compounds of formula I wherein n is 1, 2 or 3; R1 is H, C1-4alkyl, aryl, or aryl-C1-4alkyl; Y is C1-4alkylene, —CO—C1-4alkylene, —CO—C2-5alkenylene, —CO—NH—, —CO—C1-3alkylene-NH—, or —CO—O—; R2 is an aromatic or heteroaromatic residue, each being optionally substituted by CF3, halogen, OH, C1-4alkoxy, amino, mono- or di-C1-4alkyl substituted amino, phenyl, benzyl or C1-4alkyl optionally substituted by amino; R3is the side chain present on the C&agr; of an &agr;-amino acid; R4 is biphenylyl, benzyl, hydroxy-benzyl, &agr;- or &bgr;-naphthyl-methyl, 5,6,7,8-tetrahydro-&bgr;-naphthyl-methyl or indolyl-methyl, each being optionally substituted on the ring by CF3, halogen, OH, C1-4alkoxy, amino, mono- or di-C1-4alkyl substituted amino, phenyl, benzyl or C1-4alkyl optionally substituted by amino; and X is —CN, —NR5R6 or —O—R8 wherein R5 is H, C1-6alkyl, aryl or aryl-C1-4alkyl; R6 is H or C1-6alkyl; and R8 is H, C1-4alkyl, aryl or aryl-C1-4alkyl; in free form or in salt form; which are useful in preventing or treating disorders or diseases mediated by LFA-1/ICAM-1, -ICAM-2 or -ICAM-3 interactions.

  公式I的化合物，其中n为1、2或3；R1为H、C1-4烷基、芳基或芳基-C1-4烷基；Y为C1-4亚烷基、-CO-C1-4亚烷基、-CO-C2-5烯基亚烷基、-CO-NH-、-CO-C1-3亚烷基-NH-或-CO-O-；R2为芳香基或杂芳香基残基，每个残基可选择地被CF3、卤素、OH、C1-4烷氧基、氨基、单烷基或双烷基取代的氨基、苯基、苄基或可选择地被氨基取代的C1-4烷基取代；R3是存在于α-氨基酸的Cα上的侧链；R4为联苯基、苄基、羟基苄基、α-或β-萘基-甲基、5,6,7,8-四氢-β-萘基-甲基或吲哚基-甲基，每个残基可选择地被CF3、卤素、OH、C1-4烷氧基、氨基、单烷基或双烷基取代的氨基、苯基、苄基或可选择地被氨基取代的C1-4烷基取代；X为-CN、-NR5R6或-O-R8，其中R5为H、C1-6烷基、芳基或芳基-C1-4烷基；R6为H或C1-6烷基；R8为H、C1-4烷基、芳基或芳基-C1-4烷基；以自由形式或盐形式存在；用于预防或治疗由LFA-1/ICAM-1、-ICAM-2或-ICAM-3相互作用介导的疾病或疾病的有用化合物。
• SUBSTITUTED DIAZEPANS
  申请人：Novartis AG

  公开号：EP1220852B1

  公开（公告）日：2006-01-18
• US6399599B1
  申请人：——

  公开号：US6399599B1

  公开（公告）日：2002-06-04
• [EN] SUBSTITUTED DIAZEPANES<br/>[FR] DIAZEPANS SUBSTITUES
  申请人：NOVARTIS AG

  公开号：WO2001027102A1

  公开（公告）日：2001-04-19

  The invention provides novel diazepanes having interesting pharmaceutical properties, particularly in preventing or treating disorders or diseases mediated by LFA-1/ICAM-1, -ICAM-2 or -ICAM-3 interactions.
• 1,4-Diazepane-2-ones as novel inhibitors of LFA-1
  作者：Sompong Wattanasin、Rainer Albert、Claus Ehrhardt、Didier Roche、Michael Sabio、Ulrich Hommel、Karl Welzenbach、Gabriele Weitz-Schmidt

  DOI：10.1016/s0960-894x(02)00991-5

  日期：2003.2

  The design, synthesis, and biological evaluation of 1,4-diazepane-2-ones as novel LFA-1 antagonists from a scaffold-based combinatorial library are described. Initial optimization of the library lead has resulted in high-affinity antagonists of the LFA-1/ICAM-1 interaction, such as compounds 18d and 18e with IC50 values of 110 and 70 nM, respectively. (C) 2002 Elsevier Science Ltd. All rights reserved.