2-(5-methylpyridin-2-yl)-1-[2-[(1R)-5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonan-7-yl]ethanone | 1334782-83-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-(5-methylpyridin-2-yl)-1-[2-[(1R)-5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonan-7-yl]ethanone
• CAS: 1334782-83-0
• 化学式: C₂₈H₃₁N₅O
• 分子量: 453.587
• InChiKey: AAJDKMBUXCOQNC-RUZDIDTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  62.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  tert-butyl 4-(chloromethyl)-4-formylpiperidine-1-carboxylate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 sodium cyanoborohydride 、 potassium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 41.0h， 生成 2-(5-methylpyridin-2-yl)-1-[2-[(1R)-5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonan-7-yl]ethanone
  参考文献：
  名称：

  Identification of potent, selective, CNS-targeted inverse agonists of the ghrelin receptor

  摘要：

  The optimization for selectivity and central receptor occupancy for a series of spirocyclic azetidine-piperidine inverse agonists of the ghrelin receptor is described. Decreased mAChR muscarinic M2 binding was achieved by use of a chiral indane in place of a substituted benzylic group. Compounds with desirable balance of human in vitro clearance and ex vivo central receptor occupancy were discovered by incorporation of heterocycles. Specifically, heteroaryl rings with nitrogen(s) vicinal to the indane linkage provided the most attractive overall properties. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.044

文献信息

• Identification of potent, selective, CNS-targeted inverse agonists of the ghrelin receptor
  作者：Kim F. McClure、Margaret Jackson、Kimberly O. Cameron、Daniel W. Kung、David A. Perry、Suvi T.M. Orr、Yingxin Zhang、Jeffrey Kohrt、Meihua Tu、Hua Gao、Dilinie Fernando、Ryan Jones、Noe Erasga、Guoqiang Wang、Jana Polivkova、Wenhua Jiao、Roger Swartz、Hirokazu Ueno、Samit K. Bhattacharya、Ingrid A. Stock、Sam Varma、Victoria Bagdasarian、Sylvie Perez、Dawn Kelly-Sullivan、Ruduan Wang、Jimmy Kong、Peter Cornelius、Laura Michael、Eunsun Lee、Ann Janssen、Stefanus J. Steyn、Kimberly Lapham、Theunis Goosen

  DOI：10.1016/j.bmcl.2013.07.044

  日期：2013.10

  The optimization for selectivity and central receptor occupancy for a series of spirocyclic azetidine-piperidine inverse agonists of the ghrelin receptor is described. Decreased mAChR muscarinic M2 binding was achieved by use of a chiral indane in place of a substituted benzylic group. Compounds with desirable balance of human in vitro clearance and ex vivo central receptor occupancy were discovered by incorporation of heterocycles. Specifically, heteroaryl rings with nitrogen(s) vicinal to the indane linkage provided the most attractive overall properties. (C) 2013 Elsevier Ltd. All rights reserved.