methyl (S)-2-(4-bromo-2-nitrophenoxy)propanoate

• 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: methyl (S)-2-(4-bromo-2-nitrophenoxy)propanoate
• 英文别名: methyl (2S)-2-(4-bromo-2-nitrophenoxy)propanoate
• 化学式: C₁₀H₁₀BrNO₅
• 分子量: 304.097
• InChiKey: NISKOKKVZBPIRY-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  81.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (S)-2-(4-bromo-2-nitrophenoxy)propanoate 在 吡啶 、 盐酸 、 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 dimethyl sulfide borane 、 铁粉 、 溶剂黄146 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 甲苯 为溶剂， 反应 5.5h， 生成 1,1,1-trifluoro-2-methylpropan-2-yl (S)-(4-((3-ethoxy-1-ethyl-1H-pyrazol-4-yl)sulfonyl)-2-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)carbamate
  参考文献：
  名称：

  [EN] TETRAHYDRONAPHTHYRIDINE, BENZOXAZINE, AZA-BENZOXAZINE, AND RELATED BICYCLIC COMPOUNDS FOR INHIBITION OF RORgamma ACTIVITY AND THE TREATMENT OF DISEASE
  [FR] TÉTRAHYDRONAPHTYRIDINE, BENZOXAZINE, AZA-BENZOXAZINE ET COMPOSÉS BICYCLIQUES APPARENTÉS POUR L'INHIBITION DE L'ACTIVITÉ DE RORGAMMA ET LE TRAITEMENT DE MALADIE

  摘要：

  这项发明提供了公式（I）的某些双环杂环化合物或其药学上可接受的盐，其中X1、X2、R1、R2、R3、R4和Cy如本文所定义。该发明还提供了包括公式（I）的这种化合物或其药学上可接受的盐的药物组合物，以及使用公式（I）的这种化合物或其药学上可接受的盐或包含相同的药物组合物治疗由RORgammaT介导的疾病或症状的方法。

  公开号：

  WO2015095795A1
• 作为产物：
  描述：

  D-(+)-乳酸甲酯 、 4-溴-2-硝基苯酚 在 PS-PPh3 、 偶氮二甲酸二异丙酯 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 生成 methyl (S)-2-(4-bromo-2-nitrophenoxy)propanoate
  参考文献：
  名称：

  Rational design of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as small molecule renin inhibitors

  摘要：

  We report the design and synthesis of a series of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as orally bioavailable small molecule inhibitors of renin. Compounds with a 2-methyl-2-aryl substitution pattern exhibit potent renin inhibition and good permeability, solubility, and metabolic stability. Oral bioavailability was found to be dependent on metabolic clearance and cellular permeability, and was optimized through modulation of the sidechain that binds in the S3(sp) subsite.

  DOI：

  10.1016/j.bmc.2007.05.069

文献信息

• Tetrahydronaphthyridine, benzoxazine, aza-benzoxazine and related bicyclic compounds for inhibition of RORgamma activity and the treatment of disease
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10221146B2

  公开（公告）日：2019-03-05

  The invention provides certain bicyclic heterocyclic compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein X1, X2, R1, R2, R3, R4, and Cy are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds of the Formula (I) or pharmaceutically acceptable salts thereof, and methods of using the compounds of the Formula (I) or pharmaceutically acceptable salts thereof or pharmaceutical compositions comprising the same for treating diseases or conditions mediated by RORgammaT.

  本发明提供了某些式（I）的双环杂环化合物或其药学上可接受的盐，其中X1、X2、R1、R2、R3、R4和Cy如本文所定义。本发明还提供了包含这类式(I)化合物或其药学上可接受的盐的药物组合物，以及使用式(I)化合物或其药学上可接受的盐或包含它们的药物组合物治疗由RORgammaT介导的疾病或病症的方法。
• TETRAHYDRONAPHTHYRIDINE, BENZOXAZINE, AZA-BENZOXAZINE AND RELATED BICYCLIC COMPOUNDS FOR INHIBITION OF RORgamma ACTIVITY AND THE TREATMENT OF DISEASE
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US20160304476A1

  公开（公告）日：2016-10-20

  The invention provides certain bicylic heterocyclic compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein X 1 , X 2 , R 1 , R 2 , R 3 , R4, and Cy are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds of the Formula (I) or pharmaceutically acceptable salts thereof, and methods of using the compounds of the Formula (I) or pharmaceutically acceptable salts thereof or pharmaceutical compositions comprising the same for treating diseases or conditions mediated by RORgammaT.
• US9809561B2
  申请人：——

  公开号：US9809561B2

  公开（公告）日：2017-11-07
• Rational design of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as small molecule renin inhibitors
  作者：Noel A. Powell、Fred L. Ciske、Cuiman Cai、Daniel D. Holsworth、Ken Mennen、Chad A. Van Huis、Mehran Jalaie、Jacqueline Day、Michelle Mastronardi、Pat McConnell、Igor Mochalkin、Erli Zhang、Michael J. Ryan、John Bryant、Wendy Collard、Suzie Ferreira、Chungang Gu、Roxane Collins、Jeremy J. Edmunds

  DOI：10.1016/j.bmc.2007.05.069

  日期：2007.9

  We report the design and synthesis of a series of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as orally bioavailable small molecule inhibitors of renin. Compounds with a 2-methyl-2-aryl substitution pattern exhibit potent renin inhibition and good permeability, solubility, and metabolic stability. Oral bioavailability was found to be dependent on metabolic clearance and cellular permeability, and was optimized through modulation of the sidechain that binds in the S3(sp) subsite.
• [EN] TETRAHYDRONAPHTHYRIDINE, BENZOXAZINE, AZA-BENZOXAZINE, AND RELATED BICYCLIC COMPOUNDS FOR INHIBITION OF RORgamma ACTIVITY AND THE TREATMENT OF DISEASE<br/>[FR] TÉTRAHYDRONAPHTYRIDINE, BENZOXAZINE, AZA-BENZOXAZINE ET COMPOSÉS BICYCLIQUES APPARENTÉS POUR L'INHIBITION DE L'ACTIVITÉ DE RORGAMMA ET LE TRAITEMENT DE MALADIE
  申请人：MERCK SHARP & DOHME

  公开号：WO2015095795A1

  公开（公告）日：2015-06-25

  The invention provides certain bicylic heterocyclic compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein X1, X2, R1, R2, R3, R4, and Cy are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds of the Formula (I) or pharmaceutically acceptable salts thereof, and methods of using the compounds of the Formula (I) or pharmaceutically acceptable salts thereof or pharmaceutical compositions comprising the same for treating diseases or conditions mediated by RORgammaT.

  这项发明提供了公式（I）的某些双环杂环化合物或其药学上可接受的盐，其中X1、X2、R1、R2、R3、R4和Cy如本文所定义。该发明还提供了包括公式（I）的这种化合物或其药学上可接受的盐的药物组合物，以及使用公式（I）的这种化合物或其药学上可接受的盐或包含相同的药物组合物治疗由RORgammaT介导的疾病或症状的方法。