AMG0309 | 861877-51-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: AMG0309
• 英文别名: 6-[(6,7-dimethoxy-4-quinolinyl)oxy]-N-3-isoxazolyl-1-Naphthalenecarboxamide；6-(6,7-dimethoxyquinolin-4-yl)oxy-N-(1,2-oxazol-3-yl)naphthalene-1-carboxamide
• CAS: 861877-51-2
• 化学式: C₂₅H₁₉N₃O₅
• 分子量: 441.443
• InChiKey: COUVYKNBQZOXLF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  95.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-氨基异恶唑 、 6-(6,7-dimethoxyquinolin-4-yloxy)-1-naphthoic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以31.5%的产率得到AMG0309
  参考文献：
  名称：

  Small molecules with potent osteogenic-inducing activity in osteoblast cells

  摘要：

  A chemical screen of 45,000 compounds from a diverse collection led to the identification of two series of small molecules with potent osteogenic activity in mouse MC3T3-E1 osteoblast cells. The first chemical group was characterized by an amino benzothiazole core (AMG0892 series) and the second group by a naphthyl amide core (AMG0309 series). Using alkaline phosphatase (ALP), osteocalcin (OCL) and calcium as markers of osteoblast differentiation and mineralization, both chemical series showed EC(50)s in the 0.01-0.2 mu M range and were consistent for all three markers. Compounds inhibited cell proliferation, had no effect on apoptosis and showed evidence for CREB pathway activity. The present compounds represent some of the most potent osteogenic small molecules reported to date and provide new tools for elucidating signaling mechanisms in osteoblasts. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.01.025

文献信息

• Compounds and methods of use
  申请人：Potashman Michele

  公开号：US20060241115A1

  公开（公告）日：2006-10-26

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选化合物对于预防和治疗HGF介导的疾病等具有有效性。本发明涵盖了新颖的化合物、类似物、前药和其药学上可接受的盐，以及用于预防和治疗涉及癌症等疾病和其他疾病或状况的药物组合物和方法。该发明还涉及制备此类化合物的过程，以及在此类过程中有用的中间体。
• Naphthamides as Novel and Potent Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors: Design, Synthesis, and Evaluation
  作者：Jean-Christophe Harmange、Matthew M. Weiss、Julie Germain、Anthony J. Polverino、George Borg、James Bready、Danlin Chen、Deborah Choquette、Angela Coxon、Tom DeMelfi、Lucian DiPietro、Nicholas Doerr、Juan Estrada、Julie Flynn、Russell F. Graceffa、Shawn P. Harriman、Stephen Kaufman、Daniel S. La、Alexander Long、Matthew W. Martin、Sesha Neervannan、Vinod F. Patel、Michele Potashman、Kelly Regal、Phillip M. Roveto、Michael L. Schrag、Charlie Starnes、Andrew Tasker、Yohannes Teffera、Ling Wang、Ryan D. White、Douglas A. Whittington、Roger Zanon

  DOI：10.1021/jm701097z

  日期：2008.3.1

  A series of naphthyl-based compounds were synthesized as potential inhibitors of vascular endothelial growth factor (VEGF) receptors. Investigations of structure-activity relationships led to the identification of a series of naphthamides that are potent inhibitors of the VEGF receptor tyrosine kinase family. Numerous analogues demonstrated low nanomolar inhibition of VEGF-dependent human umbilical vein endothelial cell (HUVEC) proliferation, and of these several compounds possessed favorable pharmacokinetic (PK) profiles. In particular, compound 48 demonstrated significant antitumor efficacy against established HT29 human colon adenocarcinoma xenografts implanted in athymic mice. A full account of the preparation, structure-activity relationships, pharmacokinetic properties, and pharmacology of analogues within this series is presented.
• COMPOUNDS AND METHODS OF USE
  申请人：AMGEN INC.

  公开号：EP1713484A2

  公开（公告）日：2006-10-25
• JP2007518824A
  申请人：——

  公开号：JP2007518824A

  公开（公告）日：2007-07-12
• US7435823B2
  申请人：——

  公开号：US7435823B2

  公开（公告）日：2008-10-14