Methyl 3-(1,3-benzodioxol-5-yl)-3-[6-(3-fluoro-2-nitrophenoxy)-1-oxo-3,4-dihydroisoquinolin-2-yl]propanoate | 866083-12-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: Methyl 3-(1,3-benzodioxol-5-yl)-3-[6-(3-fluoro-2-nitrophenoxy)-1-oxo-3,4-dihydroisoquinolin-2-yl]propanoate
• CAS: 866083-12-7
• 化学式: C₂₆H₂₁FN₂O₈
• 分子量: 508.46
• InChiKey: CNSQWPVLWOXEFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  120
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Methyl 3-(1,3-benzodioxol-5-yl)-3-[6-(3-fluoro-2-nitrophenoxy)-1-oxo-3,4-dihydroisoquinolin-2-yl]propanoate 在 氯化亚砜 、 10% palladium on activated carbon 、 水 、 氢气 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 乙醇 为溶剂， 60.0~120.0 ℃ 、101.33 kPa 条件下， 生成 3-Benzo[1,3]dioxol-5-yl-3-[1-oxo-6-(1,2,3,4-tetrahydro-benzo[4,5]imidazo[1,2-a]pyrimidin-9-yloxy)-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid
  参考文献：
  名称：

  Synthesis and initial evaluation of novel, non-peptidic antagonists of the αv-integrins αvβ3 and αvβ5

  摘要：

  The discovery, synthesis and preliminary SAR of a novel class of non-peptidic antagonists of the alpha(v)-integrins alpha(v)beta(3) and alpha(v)beta(5) is described. High-throughput screening of an extensive series of ECLiPS (TM) compound libraries led to the identification of compound 1 as a dual inhibitor of the alpha(v)-integrins alpha(v)beta(3) and alpha(v)beta(5). Optimization of compound 1 involving, in part, introduction of two novel constraints led to the discovery of compounds 15a and 15b with reduced PSA and much improved potency for both the alpha(v)beta(3) and alpha(v)beta(5) integrins. Compounds 15a and 15b were shown to have promising activity in functional cellular assays and compound 15a also exhibited a promising Caco-2 permeability profile. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.074
• 作为产物：
  描述：

  6-羟基-3,4-二氢异喹啉-1(2H)-酮 在 10% palladium on activated carbon 、 氢气 、 potassium carbonate 、 caesium carbonate 、 对甲苯磺酸 、 ytterbium(III) triflate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 80.0 ℃ 、101.33 kPa 条件下， 生成 Methyl 3-(1,3-benzodioxol-5-yl)-3-[6-(3-fluoro-2-nitrophenoxy)-1-oxo-3,4-dihydroisoquinolin-2-yl]propanoate
  参考文献：
  名称：

  Synthesis and initial evaluation of novel, non-peptidic antagonists of the αv-integrins αvβ3 and αvβ5

  摘要：

  The discovery, synthesis and preliminary SAR of a novel class of non-peptidic antagonists of the alpha(v)-integrins alpha(v)beta(3) and alpha(v)beta(5) is described. High-throughput screening of an extensive series of ECLiPS (TM) compound libraries led to the identification of compound 1 as a dual inhibitor of the alpha(v)-integrins alpha(v)beta(3) and alpha(v)beta(5). Optimization of compound 1 involving, in part, introduction of two novel constraints led to the discovery of compounds 15a and 15b with reduced PSA and much improved potency for both the alpha(v)beta(3) and alpha(v)beta(5) integrins. Compounds 15a and 15b were shown to have promising activity in functional cellular assays and compound 15a also exhibited a promising Caco-2 permeability profile. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.074

文献信息

• Nitrogen heterocycle biaryls for osteoporosis and other diseases
  申请人：Letourneau John Jeffrey

  公开号：US20050222203A1

  公开（公告）日：2005-10-06

  Nitrogen heterocycle biaryls having a carboxylate terminus are useful for treating endometriosis, osteoporosis, restenosis following angioplasty, rheumatoid arthritis, cancer, macular degeneration and obesity. Compounds of formula: are disclosed. A representative example is

  氮杂环联苯具有羧酸末端，可用于治疗子宫内膜异位症、骨质疏松症、血管成形术后再狭窄、类风湿关节炎、癌症、黄斑变性和肥胖症。 公开了以下化合物的结构： 代表性示例是
• WO2007/1249
  申请人：——

  公开号：——

  公开（公告）日：——
• US7365209B2
  申请人：——

  公开号：US7365209B2

  公开（公告）日：2008-04-29
• [EN] NITROGEN HETEROCYCLE BIARYLS FOR OSTEOPOROSIS AND OTHER DISEASES<br/>[FR] BIARYLES À HÉTÉROCYCLE AZOTE POUR L'OSTÉOPOROSE ET D'AUTRES MALADIES
  申请人：PHARMACOPEIA DRUG DISCOVERY

  公开号：WO2007001249A1

  公开（公告）日：2007-01-04

  [EN] Nitrogen heterocycle biaryls having a carboxylate terminus are useful for treating endometriosis, osteoporosis, restenosis following angioplasty, rheumatoid arthritis, cancer, macular degeneration and obesity. Compounds of formula: (I) are disclosed. A representative example is : (II)
  [FR] La présente invention concerne des biaryles à hétérocycle azote qui possèdent une extrémité carboxylate et qui sont utiles pour le traitement de l'endométriose, de l'ostéoporose, de la resténose après angioplastie, de la polyarthrite rhumatoïde, du cancer, de la dégénérescence maculaire et de l'obésité. Des composés de formule : (I) sont présentés. Un exemple représentatif est : (II)
• Synthesis and initial evaluation of novel, non-peptidic antagonists of the αv-integrins αvβ3 and αvβ5
  作者：Jeffrey J. Letourneau、Jinqi Liu、Michael H.J. Ohlmeyer、Chris Riviello、Yajing Rong、Hong Li、Kenneth C. Appell、Shalini Bansal、Biji Jacob、Angela Wong、Maria L. Webb

  DOI：10.1016/j.bmcl.2008.11.074

  日期：2009.1

  The discovery, synthesis and preliminary SAR of a novel class of non-peptidic antagonists of the alpha(v)-integrins alpha(v)beta(3) and alpha(v)beta(5) is described. High-throughput screening of an extensive series of ECLiPS (TM) compound libraries led to the identification of compound 1 as a dual inhibitor of the alpha(v)-integrins alpha(v)beta(3) and alpha(v)beta(5). Optimization of compound 1 involving, in part, introduction of two novel constraints led to the discovery of compounds 15a and 15b with reduced PSA and much improved potency for both the alpha(v)beta(3) and alpha(v)beta(5) integrins. Compounds 15a and 15b were shown to have promising activity in functional cellular assays and compound 15a also exhibited a promising Caco-2 permeability profile. (C) 2009 Elsevier Ltd. All rights reserved.