(4S)-4-amino-5-[[(2S)-1-[[(2S)-1-[[(2S,3R)-4-(3,5-dichloroanilino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid | 753030-42-1

• 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: (4S)-4-amino-5-[[(2S)-1-[[(2S)-1-[[(2S,3R)-4-(3,5-dichloroanilino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid
• CAS: 753030-42-1
• 化学式: C₃₂H₄₃Cl₂N₅O₇
• 分子量: 680.629
• InChiKey: SFMIGNKEHGMRPI-WZFFGLSISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  46
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  200
• 氢给体数：
  7
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 盐酸 、 苯甲醚 作用下， 以 1,4-二氧六环 为溶剂， 生成 (4S)-4-amino-5-[[(2S)-1-[[(2S)-1-[[(2S,3R)-4-(3,5-dichloroanilino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid
  参考文献：
  名称：

  BACE1 inhibitors: Optimization by replacing the P1′ residue with non-acidic moiety

  摘要：

  Recently, we reported potent BACE1 inhibitors KMI-429, -684, and -574 possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. These inhibitors showed potent inhibitory activities in enzymatic and cell assays, especially, KMI-429 was confirmed to significantly inhibit A beta production in vivo. However, acidic moieties at the P-4 and P-1' positions of KMI-compounds were thought to be unfavorable for membrane permeability across the blood-brain barrier. Herein, we replaced acidic moieties at the P-4 position with other hydrogen bond acceptor groups, and these inhibitors exhibited improved BACE1 inhibitory activities in cultured cells. In this study, we replaced the acidic moieties at the P-1' position with non-acidic and low molecular sized moieties. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.058

文献信息

• Peptide derivatives having beta-secretase inhibitory activity
  申请人：Kiso Yoshiaki

  公开号：US20070004637A1

  公开（公告）日：2007-01-04

  Provided are excellent β-secretase inhibitors, that is, compounds represented by the general formula (1) or prodrugs thereof: wherein A is amino or protected amino; B 1 and B 2 are each a single bond, alkylene of 1 to 3 carbon atoms, or the like; D is a single bond, —NHCO, or the like; E is —COOH, tetrazole ring, or the like; n is an integer of 1 to 3; m is an integer of 1 to 3; G is hydroxyl, a group represented by the general formula (2), or the like: in which Z is —NH, -Asp-Ala-NH—, -Asp-Ala-, -Asp-NH—, or the like; L is a 5-to 10-membered ring optionally containing a heteroatom and/or unsaturated bond; X is —COOH, tetrazole ring, or the like; Y is hydrogen, —COOH, or the like; and k is an integer of 1 to 4; and R 1 , R 2 , and R 3 are each alkyl of 1 to 6 carbon atoms, or the like.
• US7312188B2
  申请人：——

  公开号：US7312188B2

  公开（公告）日：2007-12-25