N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-(1,3-dioxoisoindol-2-yl)-4-spiro[indene-1,4'-piperidine]-1'-ylbutanamide | 691875-73-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-(1,3-dioxoisoindol-2-yl)-4-spiro[indene-1,4'-piperidine]-1'-ylbutanamide
• CAS: 691875-73-7
• 化学式: C₃₄H₂₉F₆N₃O₃
• 分子量: 641.613
• InChiKey: SZRNFKNSHZUSAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  46
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-(1,3-dioxoisoindol-2-yl)-4-spiro[indene-1,4'-piperidine]-1'-ylbutanamide 在 肼 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 2-amino-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-spiro[indene-1,4'-piperidine]-1'-ylbutanamide
  参考文献：
  名称：

  4-Amino-2-alkyl-butyramides as small molecule CCR2 antagonists with favorable pharmacokinetic properties

  摘要：

  A systematic examination of the central aromatic portion of the lead (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-(4-fluorophenyl)-4-(1'H-spiro[indene-1,4'-piperidin]-1'-yl)butanamide (9) led to the discovery of a novel class of CCR2 receptor antagonists, which carry small alicyclic groups such as cyclopropyl, cylobutyl, or cyclopropylmethyl attached at C-2 of the carbon backbone. The most potent compound discovered, namely (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-cyclopropyl-4-[(1R,3'R)-3'-methyl-1'H-spiro[indene-1,4'-piperidin]-1'-yl]butanamide (29), showed very high binding affinity (IC50 = 4 nM, human monocyte) and excellent selectivity toward other related chemokine receptors. The excellent pharmacokinetic profile of this new lead compound allows for extensive in vivo evaluation. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.011
• 作为产物：
  描述：

  (RS)-N-邻苯二甲酰基-2-氨基-4-戊烯酸 在 lithium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 三乙酰氧基硼氢化钠 、 臭氧 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 1,4-二氧六环 、 乙醚 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 生成 N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-(1,3-dioxoisoindol-2-yl)-4-spiro[indene-1,4'-piperidine]-1'-ylbutanamide
  参考文献：
  名称：

  4-Amino-2-alkyl-butyramides as small molecule CCR2 antagonists with favorable pharmacokinetic properties

  摘要：

  A systematic examination of the central aromatic portion of the lead (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-(4-fluorophenyl)-4-(1'H-spiro[indene-1,4'-piperidin]-1'-yl)butanamide (9) led to the discovery of a novel class of CCR2 receptor antagonists, which carry small alicyclic groups such as cyclopropyl, cylobutyl, or cyclopropylmethyl attached at C-2 of the carbon backbone. The most potent compound discovered, namely (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-cyclopropyl-4-[(1R,3'R)-3'-methyl-1'H-spiro[indene-1,4'-piperidin]-1'-yl]butanamide (29), showed very high binding affinity (IC50 = 4 nM, human monocyte) and excellent selectivity toward other related chemokine receptors. The excellent pharmacokinetic profile of this new lead compound allows for extensive in vivo evaluation. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.011

文献信息

• [EN] GAMMA-AMINOAMIDE MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY<br/>[FR] MODULATEURS GAMMA-AMINOAMIDES DE L'ACTIVITE DE RECEPTEUR DE CHIMIOKINE
  申请人：MERCK & CO INC

  公开号：WO2004041279A1

  公开（公告）日：2004-05-21

  The present invention is directed to compounds of the formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, R11, R12, W, X, and n are defined herein, which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptor CCR-2.

  本发明涉及式(I)的化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R11、R12、W、X和n在此处定义，这些化合物可用作趋化因子受体活性的调节剂。特别是，这些化合物可用作趋化因子受体CCR-2的调节剂。
• US7247725B2
  申请人：——

  公开号：US7247725B2

  公开（公告）日：2007-07-24
• 4-Amino-2-alkyl-butyramides as small molecule CCR2 antagonists with favorable pharmacokinetic properties
  作者：Gabor Butora、Gregori J. Morriello、Shankaran Kothandaraman、Deodialsingh Guiadeen、Alexander Pasternak、William H. Parsons、Malcolm MacCoss、Pasquale P. Vicario、Margaret A. Cascieri、Lihu Yang

  DOI：10.1016/j.bmcl.2006.07.011

  日期：2006.9

  A systematic examination of the central aromatic portion of the lead (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-(4-fluorophenyl)-4-(1'H-spiro[indene-1,4'-piperidin]-1'-yl)butanamide (9) led to the discovery of a novel class of CCR2 receptor antagonists, which carry small alicyclic groups such as cyclopropyl, cylobutyl, or cyclopropylmethyl attached at C-2 of the carbon backbone. The most potent compound discovered, namely (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-cyclopropyl-4-[(1R,3'R)-3'-methyl-1'H-spiro[indene-1,4'-piperidin]-1'-yl]butanamide (29), showed very high binding affinity (IC50 = 4 nM, human monocyte) and excellent selectivity toward other related chemokine receptors. The excellent pharmacokinetic profile of this new lead compound allows for extensive in vivo evaluation. (c) 2006 Elsevier Ltd. All rights reserved.