(S)-1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-cyclopentylurea | 939416-56-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (S)-1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-cyclopentylurea
• 英文别名: 1-[(1S)-1-(5-chloropyridin-2-yl)-1-[3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-phenylethyl]-3-cyclopentylurea
• CAS: 939416-56-5
• 化学式: C₂₇H₂₅ClF₅N₃O₂
• 分子量: 553.959
• InChiKey: DLEGYAJVPJEXJD-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  63.2
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethanamine 在 chiral SFC 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 生成 (S)-1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-cyclopentylurea
  参考文献：
  名称：

  Diphenylpyridylethanamine (DPPE) Derivatives as Cholesteryl Ester Transfer Protein (CETP) Inhibitors

  摘要：

  A series of diphenylpyridylethanamine (DPPE) derivatives was identified exhibiting potent CETP inhibition. Replacing the labile ester functionality in the initial lead 7 generated a series of amides and ureas. Further optimization of the DPPE series for potency resulted in the discovery of cyclopentylurea 15d, which demonstrated a reduction in cholesterol ester transfer activity (48% of predose level) in hCETP/apoB-100 dual transgenic mice. The PK profile of 15d was suboptimal, and further optimization of the N-terminus resulted in the discovery of amide 20 with an improved PK profile and robust efficacy in transgenic hCETP/apoB-100 mice and in hamsters. Compound 20 demonstrated no significant changes in either mean arterial blood pressure or heart rate in telemeterized rats despite sustained high exposures.

  DOI：

  10.1021/jm300611v

文献信息

• HETEROCYCLIC CETP INHIBITORS
  申请人：Salvati E. Mark

  公开号：US20070161685A1

  公开（公告）日：2007-07-12

  Compounds of formula Ia and Ib wherein A, B, C and R 1 are described herein.

  式Ia和Ib的化合物 其中A、B、C和R1 如本文所述。
• METHODS FOR DELAYING OCCURRENCE OF NEW-ONSET TYPE 2 DIABETES AND FOR SLOWING PROGRESSION OF AND TREATING TYPE 2 DIABETES
  申请人：DalCor Pharma UK Ltd Leatherhead, Zug Branch

  公开号：EP3833336A1

  公开（公告）日：2021-06-16
• METHODS FOR TREATING OR PREVENTING CARDIOVASCULAR DISORDERS AND LOWERING RISK OF CARDIOVASCULAR EVENTS
  申请人：DALCOR PHARMA UK LTD., STOCKPORT ZUG BRANCH

  公开号：US20190070178A1

  公开（公告）日：2019-03-07

  The invention provides compositions and methods useful for treating or preventing cardiovascular disorders and lowering risk of cardiovascular events.
• US7888376B2
  申请人：——

  公开号：US7888376B2

  公开（公告）日：2011-02-15
• [EN] HETEROCYCLIC CETP INHIBITORS<br/>[FR] INHIBITEURS HETEROCYCLIQUES DE CETP
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2007062342A1

  公开（公告）日：2007-05-31

  [EN] Compounds of formula (Ia) and (Ib): wherein A, B, C and R^l are described herein, are suitable as cholesteryl ester transfer protein (CETP) inhibitors.
  [FR] L'invention concerne des composés de formule (Ia) et (Ib). Dans cette formule, A, B, C et R₁ sont décrits dans la description. Ces composés sont appropriés pour servir d'inhibiteurs de la protéine de transfert des esters de cholestérol (CETP).