N1-[2(R)-hydroxy-1(S)-indanyl]-N4-hydroxy-2(R)-[[4-(2-methyl-phenyl)phenyl]methyl]butanediamide

• 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: N1-[2(R)-hydroxy-1(S)-indanyl]-N4-hydroxy-2(R)-[[4-(2-methyl-phenyl)phenyl]methyl]butanediamide
• 英文别名: (2R)-N'-hydroxy-N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-2-[[4-(2-methylphenyl)phenyl]methyl]butanediamide
• 化学式: C₂₇H₂₈N₂O₄
• 分子量: 444.53
• InChiKey: BDVACXGBIHLFIX-QQSVUBKYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  98.7
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  tert-butyl (3R)-4-[(3aR,8bS)-2,2-dimethyl-4,8b-dihydro-3aH-indeno[1,2-d][1,3]oxazol-1-yl]-4-oxo-3-[[4-(trifluoromethylsulfonyloxy)phenyl]methyl]butanoate 在 Pd-BaSO₄ palladium diacetate 、 氢气 、 sodium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三苯基膦 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 N1-[2(R)-hydroxy-1(S)-indanyl]-N4-hydroxy-2(R)-[[4-(2-methyl-phenyl)phenyl]methyl]butanediamide
  参考文献：
  名称：

  Potent P1′ biphenylmethyl substituted aggrecanase inhibitors

  摘要：

  A series of cis-1(S)2(R)-amino-2-indanol based compounds with a biphenylmethyl group at the P1' position was found to be potent aggrecanase inhibitors. Both compounds 2j and 2n possessed very high aggrecanase affinity (IC50 = 1.5 nM), and showed excellent selectivity over MMP-1 and MMP-9, with moderate selectivity against MMP-2. (C) 2001 Bristol-Myers Squibb Company. Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00704-1

文献信息

• Methods, compositions and compound assays for inhibiting amyloid-beta protein production
  申请人：Merchiers Gerard Pascal

  公开号：US20060281699A1

  公开（公告）日：2006-12-14

  A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a PROTEASE polypeptide, or fragment thereof, and measuring a compound-PROTEASE property related to the production of amyloid-beta peptide. Cellular assays of the method measure indicators including cleaved protease substrate and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of PROTEASE expression inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimer's disease.
• US6576664B1
  申请人：——

  公开号：US6576664B1

  公开（公告）日：2003-06-10
• Potent P1′ biphenylmethyl substituted aggrecanase inhibitors
  作者：Wenqing Yao、Michael Chao、Zelda R. Wasserman、Rui-Qin Liu、Maryanne B. Covington、Robert Newton、David Christ、Ruth R. Wexler、Carl P. Decicco

  DOI：10.1016/s0960-894x(01)00704-1

  日期：2002.1

  A series of cis-1(S)2(R)-amino-2-indanol based compounds with a biphenylmethyl group at the P1' position was found to be potent aggrecanase inhibitors. Both compounds 2j and 2n possessed very high aggrecanase affinity (IC50 = 1.5 nM), and showed excellent selectivity over MMP-1 and MMP-9, with moderate selectivity against MMP-2. (C) 2001 Bristol-Myers Squibb Company. Published by Elsevier Science Ltd. All rights reserved.