2-(4-methoxyphenyl)-1-{2-[(1R)-5-(pyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethanone | 1334782-54-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(4-methoxyphenyl)-1-{2-[(1R)-5-(pyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethanone
• 英文别名: (R)-7-[(4-Methoxyphenyl)acetyl]-2-(5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane；7-[(4-Methoxyphenyl)acetyl]-2-[(1R)-5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane；2-(4-methoxyphenyl)-1-[2-[(1R)-5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonan-7-yl]ethanone
• CAS: 1334782-54-5
• 化学式: C₂₉H₃₂N₄O₂
• 分子量: 468.599
• InChiKey: UHUCZYJVWVZKAH-AREMUKBSSA-N

物化性质

• 沸点：
  615.3±55.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (R)-1-azido-5-bromo-2,3-dihydro-1H-indene 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 盐酸 、 tin(II) chloride dihdyrate 、 potassium acetate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 联硼酸频那醇酯 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 91.75h， 生成 2-(4-methoxyphenyl)-1-{2-[(1R)-5-(pyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethanone
  参考文献：
  名称：

  2,3-DIHYDRO-1H-INDEN-1-YL-2,7-DIAZASPIRO[3.5] NONANE DERIVATIVES

  摘要：

  本发明提供了一种式（I）的化合物或其药用盐，其中R1、R2、Ra、L、Z、Z1和Z2如本文所定义，其作为胃泌素拮抗剂或逆向激动剂；以及其药物组合物；以及通过胃泌素受体拮抗作用治疗疾病、紊乱或病况的方法。

  公开号：

  US20110230461A1

文献信息

• 2,3-DIHYDRO-1H-INDEN-1-YL-2,7-DIAZASPIRO[3.5]NONANE DERIVATIVES
  申请人：Pfizer Inc.

  公开号：US20140080756A1

  公开（公告）日：2014-03-20

  The present invention provides a compound of Formula (I) a pharmaceutically salt thereof wherein R 1 , R 2 , Ra, L, Z, Z 1 and Z 2 are as defined herein, that act as Ghrelin antagonists or inverse agonists; pharmaceutical compositions thereof; and methods of treating diseases, disorders, or conditions mediated by the antagonism of the Ghrelin receptor.

  本发明提供了一种式为（I）的化合物及其药物盐，其中R1、R2、Ra、L、Z、Z1和Z2的定义如本文所述，该化合物作为Ghrelin拮抗剂或反向激动剂；以及其制备的药物组合物；以及治疗通过Ghrelin受体拮抗介导的疾病、疾病或病症的方法。
• 2,3-dihydro-1H-inden-1-yl-2,7-diazaspiro[3.5] nonane derivatives
  申请人：Bhattacharya Samit K.

  公开号：US08609680B2

  公开（公告）日：2013-12-17

  The present invention provides a compound of Formula (I) or a pharmaceutically salt thereof wherein R1, R2, Ra, L, Z, Z1 and Z2 are as defined herein, that act as Ghrelin antagonists or inverse agonists; pharmaceutical compositions thereof; and methods of treating diseases, disorders, or conditions mediated by the antagonism of the Ghrelin receptor.

  本发明提供了公式（I）的化合物或其药物盐，其中R1、R2、Ra、L、Z、Z1和Z2如本文所定义，其作为Ghrelin拮抗剂或反向激动剂；其药物组成物；以及治疗由Ghrelin受体拮抗引起的疾病、障碍或病况的方法。
• 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.
• Discovery of PF-5190457, a Potent, Selective, and Orally Bioavailable Ghrelin Receptor Inverse Agonist Clinical Candidate
  作者：Samit K. Bhattacharya、Kim Andrews、Ramsay Beveridge、Kimberly O. Cameron、Chiliu Chen、Matthew Dunn、Dilinie Fernando、Hua Gao、David Hepworth、V. Margaret Jackson、Vishal Khot、Jimmy Kong、Rachel E. Kosa、Kimberly Lapham、Paula M. Loria、Allyn T. Londregan、Kim F. McClure、Suvi T. M. Orr、Jigna Patel、Colin Rose、James Saenz、Ingrid A. Stock、Gregory Storer、Maria VanVolkenburg、Derek Vrieze、Guoqiang Wang、Jun Xiao、Yingxin Zhang

  DOI：10.1021/ml400473x

  日期：2014.5.8

  The identification of potent, highly selective orally bioavailable ghrelin receptor inverse agonists from a spiro-azetidino-piperidine series is described. Examples from this series have promising in vivo pharmacokinetics and increase glucose-stimulated insulin secretion in human whole and dispersed islets. A physicochemistry-based strategy to increase lipophilic efficiency for ghrelin receptor potency and retain low clearance and satisfactory permeability while reducing off-target pharmacology led to the discovery of 16h. Compound 16h has a superior balance of ghrelin receptor pharmacology and off-target selectivity. On the basis of its promising pharmacological and safety profile, 16h was advanced to human clinical trials.
• 2,3 DIHYDRO-1H-INDEN-1-YL-2,7-DIAZASPIRO[3.6]NONANE DERIVATIVES AND THEIR USE AS ANTAGONISTS OR INVERSE AGONISTS OF THE GHRELIN RECEPTOR
  申请人：Pfizer Inc.

  公开号：EP2547679B1

  公开（公告）日：2015-11-04