2-(8-(4-(tert-butyl)benzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)acetic acid | 1260000-19-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-(8-(4-(tert-butyl)benzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)acetic acid
• CAS: 1260000-19-8
• 化学式: C₂₆H₃₁N₃O₄
• 分子量: 449.55
• InChiKey: XNDKYALWPGTXIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  33.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  81.16
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-(8-(4-(tert-butyl)benzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)acetic acid 、 4-Boc-氨甲基哌啶 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 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 Tert-butyl(1-(2-(8-(4-tert-butylbenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)acetyl)piperidin-4-yl)methylcarbamate
  参考文献：
  名称：

  Spiroimidazolidinone NPC1L1 inhibitors. Part 2: Structure–activity studies and in vivo efficacy

  摘要：

  Ezetimibe (Zetia (R)), a cholesterol-absorption inhibitor (CAI) approved by the FDA for the treatment of hypercholesterolemia, is believed to target the intestine protein Niemann-Pick C1-Like 1 (NPC1L1) or its pathway. A spiroimidazolidinone NPC1L1 inhibitor identified by virtual screening showed moderate binding activity but was not efficacious in an in vivo rodent model of cholesterol absorption. Synthesis of analogs established the structure-activity relationships for binding activity, and resulted in compounds with in vivo efficacy, including 24, which inhibited plasma cholesterol absorption by 67% in the mouse, thereby providing proof-of-concept that non-beta-lactams can be effective CAIs. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.138
• 作为产物：
  描述：

  ethyl 2-(8-(4-(tert-butyl)benzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)acetate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 2-(8-(4-(tert-butyl)benzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)acetic acid
  参考文献：
  名称：

  Spiroimidazolidinone NPC1L1 inhibitors. Part 2: Structure–activity studies and in vivo efficacy

  摘要：

  Ezetimibe (Zetia (R)), a cholesterol-absorption inhibitor (CAI) approved by the FDA for the treatment of hypercholesterolemia, is believed to target the intestine protein Niemann-Pick C1-Like 1 (NPC1L1) or its pathway. A spiroimidazolidinone NPC1L1 inhibitor identified by virtual screening showed moderate binding activity but was not efficacious in an in vivo rodent model of cholesterol absorption. Synthesis of analogs established the structure-activity relationships for binding activity, and resulted in compounds with in vivo efficacy, including 24, which inhibited plasma cholesterol absorption by 67% in the mouse, thereby providing proof-of-concept that non-beta-lactams can be effective CAIs. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.138