(S)-cyclopropyl(2-fluorophenyl)methanamine | 844817-69-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-cyclopropyl(2-fluorophenyl)methanamine
• 英文别名: (S)-cyclopropyl-(2-fluorophenyl)methanamine
• CAS: 844817-69-2
• 化学式: C₁₀H₁₂FN
• 分子量: 165.21
• InChiKey: ZGPDSOISFOQZLZ-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-cyclopropyl(2-fluorophenyl)methanamine 、 3-碘-5-(1h)吲唑羧酸 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以75%的产率得到(S)-N-(cyclopropyl(2-fluorophenyl)methyl)-3-iodo-1H-indazole-5-carboxamide
  参考文献：
  名称：

  The Discovery of Orally Bioavailable Tyrosine Threonine Kinase (TTK) Inhibitors: 3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides as Anticancer Agents

  摘要：

  The acetamido and carboxamido substituted 3-(1H-indazol-3-yl)benzenesulfonamides are potent TTK inhibitors. However, they display modest ability to attenuate cancer cell growth; their physicochemical properties, and attendant pharmacokinetic parameters, are not drug-like. By eliminating the polar 3-sulfonamide group and grafting a heterocycle at the 4 position of the phenyl ring, potent inhibitors with oral exposure were obtained. An X-ray cocrystal structure and a refined binding model allowed for a structure guided approach. Systematic optimization resulted in novel TTK inhibitors, namely 3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides. Compounds incorporating the 3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl bicyclic system were potent (TTK IC50 < 10 nM, HCT116 GI(50) < 0.1 mu M), displayed low off-target activity (>500X), and microsomal stability (T-1/2 > 30 min). A subset was tested in rodent PK and mouse xenograft models of human cancer. Compound 75 (CFI-401870) recapitulated the phenotype of TTK RNAi, demonstrated in vivo tumor growth inhibition upon oral dosing, and was selected for preclinical evaluation.

  DOI：

  10.1021/jm501740a
• 作为产物：
  描述：

  在 水 、 高碘酸 作用下， 以 甲醇 为溶剂， 生成 (S)-cyclopropyl(2-fluorophenyl)methanamine
  参考文献：
  名称：

  New quinoline NK3 receptor antagonists with CNS activity

  摘要：

  Lead optimisation starting from the previously reported selective quinoline NK3 receptor antagonists tal-netant 2 (SB-223412) and 3 (SB-222200) led to the identification of 3-aminoquinoline NK3 antagonist 10 (GSK172981) with excellent CNS penetration. Investigation of a structurally related series of sulfonamides with reduced lipophilicity led to the discovery of 20 (GSK256471). Both 10 and 20 are high affinity, potent NK3 receptor antagonists which despite having different degrees of CNS penetration produced excellent NK3 receptor occupancy in an ex vivo binding study in gerbil cortex. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.12.005

文献信息

• [EN] QUINOLINE 4-CARBOXAMIDE DERIVATIVES AND THEIR USE AS NEUROKININ 3 (NK-3) RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE QUINOLEINE 4-CARBOXAMIDE ET LEUR UTILISATION COMME ANTAGONISTES DU RECEPTEUR DE LA NEUROKININE 3 (NK-3)
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2005014575A1

  公开（公告）日：2005-02-17

  The invention relates to novel quinoline derivatives, processes for their preparation, pharmaceutical compositions containing them and their use as medicaments particularly in treating disorders of the central nervous system (CNS).

  该发明涉及新型喹啉衍生物，其制备方法，含有它们的药物组合物以及它们作为药物的用途，特别是在治疗中枢神经系统（CNS）疾病方面的用途。
• ISOQUINOLINONE DERIVATIVES AS NK3 ANTAGONISTS
  申请人：Simonsen Klaus Baek

  公开号：US20090143402A1

  公开（公告）日：2009-06-04

  Isoquinolone derivatives of the general formula are provided. The compounds are NK3 antagonists and useful for the treatment of e.g. psychosis and schizophrenia.

  提供了一般化合物的异喹啉衍生物。这些化合物是NK3拮抗剂，可用于治疗精神病和精神分裂症等疾病。
• Quinoline 4-carboxamide derivatives and their use as neurokinin 3 (nk-3) receptor antagonists
  申请人：Chan Ngor Wai

  公开号：US20070142431A1

  公开（公告）日：2007-06-21

  The invention relates to novel quinoline derivatives, processes for their preparation, pharmaceutical compositions containing them and their use as medicaments particularly in treating disorders of the central nervous system (CNS).

  本发明涉及新的喹啉衍生物、其制备方法、含有它们的制药组合物以及它们作为药物的用途，特别是用于治疗中枢神经系统（CNS）疾病。
• QUINOLINE 4-CARBOXAMIDE DERIVATIVES AND THEIR USE AS NEUROKININ 3 (NK-3) RECEPTOR ANTAGONISTS
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1651632A1

  公开（公告）日：2006-05-03
• US8173639B2
  申请人：——

  公开号：US8173639B2

  公开（公告）日：2012-05-08