(+/-)-cis-methyl {2-[4-(trifluoromethyl)phenyl]-4-piperidinyl}acetate | 1263282-26-3

• 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: (+/-)-cis-methyl {2-[4-(trifluoromethyl)phenyl]-4-piperidinyl}acetate
• 英文别名: Methyl 2-(2-(4-(trifluoromethyl)phenyl)piperidin-4-YL)acetate；methyl 2-[2-[4-(trifluoromethyl)phenyl]piperidin-4-yl]acetate
• CAS: 1263282-26-3
• 化学式: C₁₅H₁₈F₃NO₂
• 分子量: 301.309
• InChiKey: QYFZCOFVQSTIRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 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：
  38.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+/-)-cis-methyl {2-[4-(trifluoromethyl)phenyl]-4-piperidinyl}acetate 在 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 、 10% Pd/C 、 四丁基氟化铵 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium iodide 、 copper(I) bromide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 异丙醇 、 甲苯 、 乙腈 为溶剂， 反应 51.42h， 生成 2-(1-(7-((5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl)oxy)-1-(4-(trifluoromethyl)phenyl)hept-2-yn-1-yl)-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)acetic acid
  参考文献：
  名称：

  Synthesis of a potent photoreactive acidic γ-secretase modulator for target identification in cells

  摘要：

  Supramolecular self-assembly of amyloidogenic peptides is closely associated with numerous pathological conditions. For instance, Alzheimers disease (AD) is characterized by abundant amyloid plaques originating from the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases. Compounds named gamma-secretase modulators (GSMs) can shift the substrate cleavage specificity of gamma-secretase toward the production of non-amyloidogenic, shorter A beta fragments. Herein, we describe the synthesis of highly potent acidic GSMs, equipped with a photoreactive diazirine moiety for photoaffinity labeling. The probes labeled the N-terminal fragment of presenilin (the catalytic subunit of gamma-secretase), supporting a mode of action involving binding to gamma-secretase. This fundamental step toward the elucidation of the molecular mechanism governing the GSM-induced shift in gamma-secretase proteolytic specificity should pave the way for the development of improved drugs against AD. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.08.034
• 作为产物：
  描述：

  methyl {2-[4-(trifluoromethyl)phenyl]-4-pyridinyl}acetate 在 盐酸 、 platinum(IV) oxide 、 氢气 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 50.0 ℃ 、344.75 kPa 条件下， 反应 3.0h， 以99%的产率得到(+/-)-cis-methyl {2-[4-(trifluoromethyl)phenyl]-4-piperidinyl}acetate
  参考文献：
  名称：

  Piperidine-derived γ-secretase modulators

  摘要：

  This Letter details the SAR of a novel series of piperidine-derived gamma-secretase modulators. Compound 10h was found to be a potent modulator in vitro, which on further pro. ling, was found to decrease A beta 42, increase A beta 38 and have no effect on A beta 40 levels. Furthermore, 10h demonstrated excellent pharmacokinetic parameters in the mouse, rat and dog in addition to good CNS penetration in the mouse. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.08.072

文献信息

• DIFLUORINATED PIPERIDINES FOR TREATMENT OF ALZHEIMER'S DISEASE AND RELATED CONDITIONS
  申请人：Stanton Matthew G.

  公开号：US20100010041A1

  公开（公告）日：2010-01-14

  Compounds of formula (I). Selectively inhibit production of Aβ(1-42) and hence find use in treatment of diseases associated with deposition of β-amyloid in the brain.

  公式为(I)的化合物，能够选择性地抑制Aβ(1-42)的产生，因此可用于治疗与β-淀粉样蛋白在大脑中沉积相关的疾病。
• PIPERIDINES AND RELATED COMPOUNDS FOR THE TREATMENT OF ALZHEIMER'S DISEASE
  申请人：Garcia Yudith

  公开号：US20100048623A1

  公开（公告）日：2010-02-25

  Compounds of formula (I) are modulators of gamma-secretase, and hence are useful in treatment of Alzheimer's disease.

  公式（I）的化合物是γ-分泌酶调节剂，因此在治疗阿尔茨海默病方面非常有用。
• WO2006/43064
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2008/85301
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] PIPERIDINES AND RELATED COMPOUNDS FOR TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] PIPÉRIDINES ET COMPOSÉS APPARENTÉS POUR TRAITER LA MALADIE D'ALZHEIMER
  申请人：MERCK SHARP & DOHME

  公开号：WO2007125364A1

  公开（公告）日：2007-11-08

  [EN] Compounds of formula (I) are modulators of gamma-secretase, and hence are useful in treatment of Alzheimer's disease.
  [FR] L'invention concerne des composés de formule (I) modulateurs de la gamma-sécrétase, et qui sont donc utiles pour traiter la maladie d'Alzheimer.