(3R,4R)-1-(tert-butoxycarbonyl)-3-(4-fluorophenyl)piperidine-4-carboxylic acid | 455955-07-4

• 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: (3R,4R)-1-(tert-butoxycarbonyl)-3-(4-fluorophenyl)piperidine-4-carboxylic acid
• 英文别名: (3R,4R)-1-tert-butoxycarbonyl-3-(4-fluorophenyl)piperidine-4-carboxylic acid；(3R*,4R*)-1-tert-butoxycarbonyl-3-(4-fluorophenyl)piperidine-4-carboxylic acid；(3R,4R)-3-(4-fluorophenyl)-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid
• CAS: 455955-07-4
• 化学式: C₁₇H₂₂FNO₄
• 分子量: 323.364
• InChiKey: VYYACTQOEBMBQB-KGLIPLIRSA-N

物化性质

• 沸点：
  453.5±45.0 °C(predicted)
• 密度：
  1.218±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R,4R)-1-(tert-butoxycarbonyl)-3-(4-fluorophenyl)piperidine-4-carboxylic acid 在 三乙酰氧基硼氢化钠 、 1H-咪唑-1-基(1H-吡唑-1-基)甲酮 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 40.0h， 生成 (3R,4R)-4-[5-(4-chlorophenyl)-1H-pyrazol-3-yl]-3-(4-fluorophenyl)-1-phenethyl-piperidin-1-ium trifluoroacetate salt
  参考文献：
  名称：

  Pyrazoles as non-classical bioisosteres in prolylcarboxypeptidase (PrCP) inhibitors

  摘要：

  Bioisosteres are integral components of modern pharmaceutical research that allow structural optimization to maximize in vivo efficacy and minimize adverse effects by selectively modifying pharmacodynamic, pharmacokinetic and physicochemical properties. A recent medicinal chemistry campaign focused on identifying small molecule inhibitors of prolylcarboxypeptidase (PrCP) initiated an investigation into the use of pyrazoles as bioisosteres for amides. The results indicate that pyrazoles are suitable bioisosteric replacements of amide functional groups. The study is an example of managing bioisosteric replacement by incorporating subsequent structural modifications to maintain potency against the selected target. A heuristic model for an embedded pharmacophore is also described. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.070

文献信息

• [EN] PROLYLCARBOXYPEPTIDASE INHIBITORS<br/>[FR] INHIBITEURS DE PROLYLCARBOXYPEPTIDASE
  申请人：MERCK SHARP & DOHME

  公开号：WO2011137012A1

  公开（公告）日：2011-11-03

  Compounds of structural formula (I) are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to the enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders.

  结构式（I）的化合物是脯氨酸羧肽酶（PrCP）的抑制剂。本发明的化合物可用于预防和治疗与PrCP酶活性相关的疾病，如异常代谢，包括肥胖症、糖尿病、代谢综合征、与肥胖相关的疾病以及与糖尿病相关的疾病。
• Acylated piperidine derivatives as melanocortin-4 receptor agonists
  申请人：——

  公开号：US20040097546A1

  公开（公告）日：2004-05-20

  Certain novel 4-substituted N-acylated piperidine derivatives are agonists of the human melanocortin receptor(s) and, in particular, are selective agonists of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the activation of MC-4R, such as obesity, diabetes, sexual dysfunction, including erectile dysfunction and female sexual dysfunction.

  某些新型4-取代N-酰化哌啶衍生物是人类黑素细胞素受体的激动剂，特别是人类黑素细胞素-4受体（MC-4R）的选择性激动剂。因此，它们可用于治疗、控制或预防对MC-4R激活敏感的疾病和障碍，如肥胖症、糖尿病、性功能障碍，包括勃起功能障碍和女性性功能障碍。
• Piperidine Compound and Process for Preparing the Same
  申请人：Miyake Tsutomu

  公开号：US20090005355A1

  公开（公告）日：2009-01-01

  The present invention is to provide a piperidine compound represented by the formula [I]: wherein Ring A is an optionally substituted benzene ring, Ring B is an optionally substituted benzene ring, R 1 is hydrogen atom or a substituent for amino group, R 2 is hydrogen atom, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted alkyl group, a substituted carbonyl group or a halogen atom, Z is oxygen atom or —N(R 3 )—, R 3 is hydrogen atom or an optionally substituted alkyl group, R 4a and R 4b may be the same or different, and each is hydrogen atom or an optionally substituted alkyl group, or may be bonded to each other at the both ends to form an alkylene group, or a pharmaceutically acceptable salt thereof, which has an excellent tachykinin receptor antagonistic action.

  本发明提供了一种由式[I]表示的哌啶化合物，其中环A是可选取代的苯环，环B是可选取代的苯环，R1是氢原子或氨基基团的取代基，R2是氢原子、可选取代的羟基、可选取代的氨基、可选取代的烷基、取代的羰基或卤素原子，Z是氧原子或-N（R3）-，R3是氢原子或可选取代的烷基，R4a和R4b可以相同也可以不同，每个是氢原子或可选取代的烷基，或者可以在两端结合形成烷基，或其药学上可接受的盐，具有优异的Tachykinin受体拮抗作用。
• NOVEL PROLYLCARBOXYPEPTIDASE INHIBITORS
  申请人：Graham Thomas H.

  公开号：US20130030019A1

  公开（公告）日：2013-01-31

  Compounds of structural formula (I) are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to the enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders.

  结构式(I)的复合物是脯氨酰羧肽酶(PrCP)的抑制剂。本发明的化合物可用于预防和治疗与PrCP酶活性相关的疾病，如异常代谢，包括肥胖症；糖尿病；代谢综合征；与肥胖相关的疾病；和与糖尿病相关的疾病。
• Prolylcarboxypeptidase inhibitors
  申请人：Graham Thomas H.

  公开号：US08921394B2

  公开（公告）日：2014-12-30

  Compounds of structural formula (I) are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to the enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders.

  结构式(I)的化合物是脯氨酸羧肽酶(PrCP)的抑制剂。本发明的化合物对于预防和治疗与PrCP酶活性相关的疾病非常有用，例如异常代谢，包括肥胖症、糖尿病、代谢综合征、肥胖相关疾病和糖尿病相关疾病。