[4-(甲基氨基)哌啶-1-基]-苯基甲酮 | 92032-54-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: [4-(甲基氨基)哌啶-1-基]-苯基甲酮
• 英文名称: 4-methylamino-1-benzoylpiperidine
• 英文别名: (4-(Methylamino)piperidin-1-yl)(phenyl)methanone；[4-(methylamino)piperidin-1-yl]-phenylmethanone
• CAS: 92032-54-7
• 化学式: C₁₃H₁₈N₂O
• mdl: MFCD12154837
• 分子量: 218.299
• InChiKey: FJOZONKRMICPLS-UHFFFAOYSA-N

物化性质

• 沸点：
  361.7±35.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  [4-(甲基氨基)哌啶-1-基]-苯基甲酮 在 吡啶 、 三甲基溴硅烷 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙腈 为溶剂， 反应 62.75h， 生成 组织蛋白酶G抑制剂
  参考文献：
  名称：

  Nonpeptide Inhibitors of Cathepsin G:  Optimization of a Novel β-Ketophosphonic Acid Lead by Structure-Based Drug Design

  摘要：

  The serine protease cathepsin G (EC 3.4.21.20; Cat G), which is stored in the azurophilic granules of neutrophils (polymorphonuclear leukocytes) and released on degranulation, has been implicated in various pathological conditions associated with inflammation. By employing high-throughput screening, we identified beta-ketophosphonic acid 1 as a moderate inhibitor of Cat G (IC(50) = 4.1 microM). We were fortunate to obtain a cocrystal of 1 with Cat G and solve its structure by X-ray crystallography (3.5 A). Structural details from the X-ray analysis of 1.Cat G served as a platform for optimization of this lead compound by structure-based drug design. With the aid of molecular modeling, substituents were attached to the 3-position of the 2-naphthyl ring of 1, which occupies the S1 pocket of Cat G, to provide an extension into the hydrophobic S3 region. Thus, we arrived at analogue 7 with an 80-fold potency improvement over 1 (IC(50) = 53 nM). From these results, it is evident that the beta-ketophosphonic acid unit can form the basis for a novel class of serine protease inhibitors.

  DOI：

  10.1021/ja017506h
• 作为产物：
  描述：

  4-叔丁氧羰基氨基哌啶 在 potassium hydride 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 [4-(甲基氨基)哌啶-1-基]-苯基甲酮
  参考文献：
  名称：

  Nonpeptide Inhibitors of Cathepsin G:  Optimization of a Novel β-Ketophosphonic Acid Lead by Structure-Based Drug Design

  摘要：

  The serine protease cathepsin G (EC 3.4.21.20; Cat G), which is stored in the azurophilic granules of neutrophils (polymorphonuclear leukocytes) and released on degranulation, has been implicated in various pathological conditions associated with inflammation. By employing high-throughput screening, we identified beta-ketophosphonic acid 1 as a moderate inhibitor of Cat G (IC(50) = 4.1 microM). We were fortunate to obtain a cocrystal of 1 with Cat G and solve its structure by X-ray crystallography (3.5 A). Structural details from the X-ray analysis of 1.Cat G served as a platform for optimization of this lead compound by structure-based drug design. With the aid of molecular modeling, substituents were attached to the 3-position of the 2-naphthyl ring of 1, which occupies the S1 pocket of Cat G, to provide an extension into the hydrophobic S3 region. Thus, we arrived at analogue 7 with an 80-fold potency improvement over 1 (IC(50) = 53 nM). From these results, it is evident that the beta-ketophosphonic acid unit can form the basis for a novel class of serine protease inhibitors.

  DOI：

  10.1021/ja017506h

文献信息

• 2-（4-吗啉基）-4,6-二取代嘧啶/均三嗪类化合物及其盐和应用
  申请人：西安交通大学

  公开号：CN107652270A

  公开（公告）日：2018-02-02

  本发明2‑(4‑吗啉基)‑4,6‑二取代嘧啶/均三嗪类化合物及其盐和应用，公开的具有2‑(4‑吗啉基)‑4‑(N‑(1‑苯甲酰基‑4‑哌啶基)氨基)‑6‑(吡啶基或嘧啶基)嘧啶或均三嗪类化合物，为具有以下通式的化合物。其中，X和Y为N或CH；R1为C1‑C3烷基；R2为氢、卤素、甲基、三氟甲基；R3为氨基、甲氧基、氰基、三氟甲基；当R2为氢、R3为氨基且Y为N时，X不为N。该类化合物及其盐类具有抑制PI3K和RAF激酶的双重活性，可同时抑制PI3K/AKT/mTOR信号转导通路和RAs/RAF/MEK/ERK信号转导通路，抗肿瘤活性更佳。本发明还公开了通式化合物作为PI3K/RAF双重抑制剂的用途。
• Sulphones which modulate the action of gammasecretase
  申请人：Castro Pineiro Luis Jose

  公开号：US20070213329A1

  公开（公告）日：2007-09-13

  Novel sulphones of Formula I are disclosed: wherein A completes a 4-7 membered ring optionally comprising up to two heteroatoms. The compounds modulate the action of γ-secretase and are therefore useful in the treatment or prevention of Alzheimer's disease.

  公开了一种化学式为I的新型磺酰类化合物：其中A形成一个4-7环，可选地包含最多两个杂原子。这些化合物调节γ-分泌酶的作用，因此可用于治疗或预防阿尔茨海默病。
• Sulphones which modulate the action of gamma secretase
  申请人：Castro Pineiro Jose Luis

  公开号：US20090131419A1

  公开（公告）日：2009-05-21

  Disclosed are sulphones which modulate the action of gamma-secretase. The compounds are useful in the treatment or prevention of Alzheimer's disease.

  公开了可以调节γ-分泌酶作用的磺酰化合物。这些化合物对治疗或预防阿尔茨海默病有用。
• New compounds
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2471787A1

  公开（公告）日：2012-07-04

  The present invention encompasses compounds of general formula (1) wherein R1 to R4 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use for preparing a medicament having the above-mentioned properties.

  本发明包括通式（1）的化合物 其中 R1 至 R4 的定义如权利要求 1 所述，它们适用于治疗以细胞过度增殖或异常增殖为特征的疾病，并可用于制备具有上述性质的药物。
• INHIBITORS OF BACTERIAL GLYCOSYL TRANSFERASES
  申请人：President and Fellows of Harvard College

  公开号：US20180162862A1

  公开（公告）日：2018-06-14

  Described herein are compounds of Formula (I′), Formula (IA), Formulae (I)-(VII), pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The invention also provides pharmaceutical compositions of the compounds for human and veterinary use. Compounds of the present invention are useful for inhibiting bacterial growth and therefore are useful in treating and/or preventing bacterial infections. Methods of using the compounds for treating and/or preventing a bacterial infection in a subject are also described.