tert-butyl 3'-methylspiro[indene-1,4'-piperidine]-1'-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚和异茚
• 英文名称: tert-butyl 3'-methylspiro[indene-1,4'-piperidine]-1'-carboxylate
• 化学式: C₁₉H₂₅NO₂
• 分子量: 299.413
• InChiKey: LPLMANBZCONQOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  tert-butyl 3'-methylspiro[indene-1,4'-piperidine]-1'-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 3'-Methylspiro[indene-1,4'-piperidine]
  参考文献：
  名称：

  [EN] INDOLINYL-, BENZOFURANYL-, AND BENZOTHIENYL- AMIDES AS MODULATORS OF CHEMOKINE RECEPTORS
  [FR] INDOLINYL-, BENZOFURANYL- ET BENZOTHIÉNYL-AMIDES CONSTITUANT DES MODULATEURS DE RÉCEPTEURS DE LA CHIMIOKINE

  摘要：

  本发明涉及一种公式(I)的化合物，或其药学上可接受的盐；其中R1-R5、X、Y、m和n如本文所定义。本发明的化合物对于治疗与CCR2受体过度表达相关的多种疾病是有用的。

  公开号：

  WO2010093578A1
• 作为产物：
  描述：

  1-(2-羟基-乙基氨基)-丙烷-2-醇 在 氯化亚砜 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 为溶剂， 反应 9.33h， 生成 tert-butyl 3'-methylspiro[indene-1,4'-piperidine]-1'-carboxylate
  参考文献：
  名称：

  Novel, Orally Bioavailable γ-Aminoamide CC Chemokine Receptor 2 (CCR2) Antagonists

  摘要：

  Through modification of a screening hit we have discovered a structurally distinct new lead, (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-(4-fluorophenyl)-4-(4-phenylpiperidin-1-yl)butanamide (11), which has subsequently served as the departure point for an ongoing program targeting CCR2 antagonists. Optimization of 11 leading to antagonists 26 and 37 is described. Antagonist 26 was shown to have good oral bioavailability in rats. Antagonist 37 had a CCR2 IC50 of 59 nM and excellent potency in a functional assay measuring inhibition of MCP-1 induced monocyte chemotaxis (IC50 of 41 nM).

  DOI：

  10.1021/jm060439n

文献信息

• Orally active, nonpeptide oxytocin antagonists
  作者：Ben E. Evans、James L. Leighton、Kenneth E. Rittle、Kevin F. Gilbert、George F. Lundell、Norman P. Gould、Doug W. Hobbs、Robert M. DiPardo、Daniel F. Veber、Douglas J. Pettibone、Bradley V. Clineschmidt、Paul S. Anderson、Roger M. Freidinger

  DOI：10.1021/jm00099a020

  日期：1992.10

  The first nonpeptide antagonists of the neurohypophyseal hormone, oxytocin (OT) are described. Derivatives of the spiroindenepiperidine ring system, these compounds include L-366,509, an orally bioavailable OT antagonist with good in vivo duration. The potential use of these agents for treatment of preterm labor and their significance as new nonpeptide ligands for peptide receptors are discussed.

  描述了神经下垂体激素催产素（OT）的第一个非肽拮抗剂。这些化合物是螺茚并哌啶环系统的衍生物，包括L-366509，这是一种口服生物可利用的OT拮抗剂，在体内具有良好的持续时间。讨论了这些药物在治疗早产中的潜在用途及其作为肽受体新的非肽配体的重要性。
• [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
• Novel, Orally Bioavailable γ-Aminoamide CC Chemokine Receptor 2 (CCR2) Antagonists
  作者：Alexander Pasternak、Dominick Marino、Pasquale P. Vicario、Julia Marie Ayala、Margaret A. Cascierri、William Parsons、Sander G. Mills、Malcolm MacCoss、Lihu Yang

  DOI：10.1021/jm060439n

  日期：2006.8.1

  Through modification of a screening hit we have discovered a structurally distinct new lead, (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-(4-fluorophenyl)-4-(4-phenylpiperidin-1-yl)butanamide (11), which has subsequently served as the departure point for an ongoing program targeting CCR2 antagonists. Optimization of 11 leading to antagonists 26 and 37 is described. Antagonist 26 was shown to have good oral bioavailability in rats. Antagonist 37 had a CCR2 IC50 of 59 nM and excellent potency in a functional assay measuring inhibition of MCP-1 induced monocyte chemotaxis (IC50 of 41 nM).
• [EN] INDOLINYL-, BENZOFURANYL-, AND BENZOTHIENYL- AMIDES AS MODULATORS OF CHEMOKINE RECEPTORS<br/>[FR] INDOLINYL-, BENZOFURANYL- ET BENZOTHIÉNYL-AMIDES CONSTITUANT DES MODULATEURS DE RÉCEPTEURS DE LA CHIMIOKINE
  申请人：GLAXO GROUP LTD

  公开号：WO2010093578A1

  公开（公告）日：2010-08-19

  The present invention relates to a compound of formula (I): or a pharmaceutically acceptable salt thereof; wherein R1-R5, X, Y, m, and n are as defined herein. Compounds of the present invention are useful for the treatment of a variety of diseases associated with overexpression of the CCR2 receptor.

  本发明涉及一种公式(I)的化合物，或其药学上可接受的盐；其中R1-R5、X、Y、m和n如本文所定义。本发明的化合物对于治疗与CCR2受体过度表达相关的多种疾病是有用的。