N-[2-[2-[4-[(1R,3'S)-5,6-difluoro-3-oxospiro[2-benzofuran-1,4'-piperidine]-3'-yl]-3-methylphenyl]phenyl]ethyl]acetamide | 1307796-10-6

• 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: N-[2-[2-[4-[(1R,3'S)-5,6-difluoro-3-oxospiro[2-benzofuran-1,4'-piperidine]-3'-yl]-3-methylphenyl]phenyl]ethyl]acetamide
• CAS: 1307796-10-6
• 化学式: C₂₉H₂₈F₂N₂O₃
• 分子量: 490.55
• InChiKey: FIFCWVYDHYLFKR-IRPSRAIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-溴-4,5-二氟苯甲酸 在 盐酸 、 sodium tetrahydroborate 、 cobalt(II) chloride hexahydrate 、 四丁基氟化铵 、 水 、 4-甲基苯磺酸吡啶 、 四丁基碘化铵 、 magnesium 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 生成 N-[2-[2-[4-[(1R,3'S)-5,6-difluoro-3-oxospiro[2-benzofuran-1,4'-piperidine]-3'-yl]-3-methylphenyl]phenyl]ethyl]acetamide
  参考文献：
  名称：

  3,4-Diarylpiperidines as potent renin inhibitors

  摘要：

  The discovery and SAR of a series of potent renin inhibitors possessing a novel 3,4-diarylpiperidine scaffold are described herein. The resulting compound 38 exhibit low nanomolar plasma renin IC50, had a clean CYP 3A4 profile and displayed micromolar affinity for the hERG channel. Furthermore, it was found to be efficacious in the double transgenic rat hypertension model and show good to moderate oral bioavailability in two animal species. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.044

文献信息

• SPIROCYCLIC PIPERIDINE DERIVATIVES USEFUL AS RENIN INHIBITORS
  申请人：Chen Austin

  公开号：US20120202837A1

  公开（公告）日：2012-08-09

  Renin inhibitors which are spirocyclic piperidine derivatives, of formula (I) and pharmaceutical compositions thereof useful in the treatment of cardiovascular diseases and renal insufficiency, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the stereoisomer thereof, wherein: n, for each instance in which it occurs, is independently 0, 1, or 2; W is a five- or six-membered saturated or unsaturated heterocyclic or carbocyclic monocyclic ring, A is (i) a five- or six-membered saturated or unsaturated heterocyclic or carbocyclic monocyclic ring or (ii) a first five- or six-membered saturated or unsaturated heterocyclic or carbocyclic ring which is fused to a second five- or six-membered saturated or unsaturated heterocyclic or carbocyclic ring, V is —(C═O)—, —CH 2 — or ═CH—; U is a bond or —CH2-, or, when V iS ═CH—, U is —CH═; X is ═CH—, ═CF—, ═C(OR 3 )—, or —(C═O)—; and Y is ═CH—, ═CF—, ═N—, or, for the case when X is —(C═O)—, Y is —N(R 3 )—.

  Renin抑制剂是一种螺环哌啶衍生物，其化学式为（I），以及其在心血管疾病和肾功能不全治疗中有用的制药组合物，或其立体异构体，或其药学上可接受的盐，或其立体异构体的药学上可接受的盐，其中：n，在每个出现的情况下，独立地为0、1或2；W为五元或六元饱和或不饱和杂环或碳环单环，A为（i）五元或六元饱和或不饱和杂环或碳环单环，或（ii）第一个与第二个五元或六元饱和或不饱和杂环或碳环单环融合的五元或六元饱和或不饱和杂环或碳环单环，V为—（C═O）—、—CH2—或═CH—；U为键或—CH2-，或当V为═CH—时，U为—CH═；X为═CH—、═CF—、═C（OR3）—或—（C═O）—；Y为═CH—、═CF—、═N—，或当X为—（C═O）—时，Y为—N（R3）—。
• 3,4-Diarylpiperidines as potent renin inhibitors
  作者：Patrick Lacombe、Mélissa Arbour、Renée Aspiotis、Elizabeth Cauchon、Austin Chen、Daniel Dubé、Jean-Pierre Falgueyret、Pierre-André Fournier、Michel Gallant、Erich Grimm、Yongxin Han、Hélène Juteau、Suzanna Liu、Christophe Mellon、Yeeman Ramtohul、Daniel Simard、René St-Jacques、Gavin Chit Tsui

  DOI：10.1016/j.bmcl.2012.01.044

  日期：2012.3

  The discovery and SAR of a series of potent renin inhibitors possessing a novel 3,4-diarylpiperidine scaffold are described herein. The resulting compound 38 exhibit low nanomolar plasma renin IC50, had a clean CYP 3A4 profile and displayed micromolar affinity for the hERG channel. Furthermore, it was found to be efficacious in the double transgenic rat hypertension model and show good to moderate oral bioavailability in two animal species. (c) 2012 Elsevier Ltd. All rights reserved.