2-chloro-7-(4-fluorophenyl)-N-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine | 1263868-52-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-chloro-7-(4-fluorophenyl)-N-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine
• CAS: 1263868-52-5
• 化学式: C₁₄H₁₃ClFN₃
• 分子量: 277.729
• InChiKey: FVGQQDRDKQCPRD-UHFFFAOYSA-N

物化性质

• 沸点：
  449.7±45.0 °C(Predicted)
• 密度：
  1.356±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline 、 2-chloro-7-(4-fluorophenyl)-N-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine 在 硫酸 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 18.0h， 以66%的产率得到7-(4-fluorophenyl)-N²-(3-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-N⁴-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine
  参考文献：
  名称：

  Identification and Preclinical Evaluation of the Bicyclic Pyrimidine γ-Secretase Modulator BMS-932481

  摘要：

  A triazine hit identified from a screen of the BMS compound collection was optimized for potency, in vivo activity, and off-target profile to produce the bicyclic pyrimidine gamma-secretase modulator BMS-932481. The compound showed robust reductions of A beta(1-42) and A beta(1-40) in the plasma, brain, and cerebrospinal fluid of mice and rats. Consistent with the gamma-secretase modulator mechanism, increases in A beta(1-37) and A beta(1-38) were observed, with no change in the total amount of A beta(1-x) produced. No Notch-based toxicity was observed, and the overall preclinical profile of BMS-932481 supported its further evaluation in human clinical trials.

  DOI：

  10.1021/acsmedchemlett.8b00541
• 作为产物：
  描述：

  diethyl 2-(4-fluorophenyl)hexanedioate 在 sodium hexamethyldisilazane 、 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 生成 2-chloro-7-(4-fluorophenyl)-N-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine
  参考文献：
  名称：

  Identification and Preclinical Evaluation of the Bicyclic Pyrimidine γ-Secretase Modulator BMS-932481

  摘要：

  A triazine hit identified from a screen of the BMS compound collection was optimized for potency, in vivo activity, and off-target profile to produce the bicyclic pyrimidine gamma-secretase modulator BMS-932481. The compound showed robust reductions of A beta(1-42) and A beta(1-40) in the plasma, brain, and cerebrospinal fluid of mice and rats. Consistent with the gamma-secretase modulator mechanism, increases in A beta(1-37) and A beta(1-38) were observed, with no change in the total amount of A beta(1-x) produced. No Notch-based toxicity was observed, and the overall preclinical profile of BMS-932481 supported its further evaluation in human clinical trials.

  DOI：

  10.1021/acsmedchemlett.8b00541

文献信息

• [EN] COMPOUNDS FOR THE REDUCTION OF ß-AMYLOID PRODUCTION<br/>[FR] COMPOSÉS POUR LA RÉDUCTION DE LA PRODUCTION DE ß-AMYLOÏDE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2012103297A1

  公开（公告）日：2012-08-02

  The present disclosure provides a series of compounds of the formula (I), which modulate β-amyloid peptide (β-ΑΡ) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by β-amyloid peptide (β-ΑΡ) production.

  本公开提供了一系列化合物的公式(I)，这些化合物调节β-淀粉样肽(β-ΑΡ)的产生，并且在治疗阿尔茨海默病和其他受β-淀粉样肽(β-ΑΡ)产生影响的疾病中有用。
• [EN] COMPOUNDS FOR THE REDUCTION OF ß-AMYLOID PRODUCTION<br/>[FR] COMPOSÉS DESTINÉS À LA RÉDUCTION DE LA PRODUCTION DE BETA-AMYLOÏDES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011014535A1

  公开（公告）日：2011-02-03

  The present disclosure provides a series of compounds of the formula (I) which modulate β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by β-amyloid peptide (β-AP) production.

  本公开提供了一系列化合物的公式(I)，这些化合物调节β-淀粉样肽(β-AP)的产生，并在治疗阿尔茨海默病和其他受β-淀粉样肽(β-AP)产生影响的疾病中有用。
• [EN] PYRIMIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRIMIDINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2019101984A1

  公开（公告）日：2019-05-31

  The invention provides new pyrimidine compounds having the general formula (I), wherein R1, R2, R3, n, and X are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.

  本发明提供了一种新的嘧啶化合物，其具有一般式（I），其中R1、R2、R3、n和X如本文所述，包括该化合物的组合物，制造该化合物的过程以及使用该化合物的方法。
• COMPOUNDS FOR THE REDUCTION OF BETA-AMYLOID PRODUCTION
  申请人：Boy Kenneth M.

  公开号：US20120028994A1

  公开（公告）日：2012-02-02

  The present disclosure provides a series of compounds of the formula (I) which modulate β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by β-amyloid peptide (β-AP) production.

  本公开提供一系列公式(I)的化合物，可调节β-淀粉样肽（β-AP）的产生，并在治疗阿尔茨海默病和其他受β-淀粉样肽（β-AP）产生影响的疾病中有用。
• Compounds for the reduction of β-amyloid production
  申请人：Boy Kenneth M.

  公开号：US08486952B2

  公开（公告）日：2013-07-16

  The present disclosure provides a series of compounds of the formula (I) which modulate β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by β-amyloid peptide (β-AP) production.

  本公开提供了一系列化合物的公式（I），其调节β-淀粉样肽（β-AP）的产生，并且在治疗阿尔茨海默病和其他受β-淀粉样肽（β-AP）产生影响的疾病中有用。