4-(3,4-dinitro-phenoxy)-2-methylsulfonyl-pyrimidine | 952490-62-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(3,4-dinitro-phenoxy)-2-methylsulfonyl-pyrimidine
• 英文别名: 4-(3,4-dinitrophenoxy)-2-methylsulfonylpyrimidine
• CAS: 952490-62-9
• 化学式: C₁₁H₈N₄O₇S
• 分子量: 340.273
• InChiKey: XRPOUGHTCWZLQO-UHFFFAOYSA-N

物化性质

• 沸点：
  579.5±60.0 °C(Predicted)
• 密度：
  1.605±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  169
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-(3,4-dinitro-phenoxy)-2-methylsulfonyl-pyrimidine 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 20.0~80.0 ℃ 、101.33 kPa 条件下， 反应 43.0h， 生成 4-(2-methylamino-pyrimidin-4-yloxy)-benzene-1,2-diamine
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Orally Active Benzimidazoles and Benzoxazoles as Vascular Endothelial Growth Factor-2 Receptor Tyrosine Kinase Inhibitors

  摘要：

  Inhibition of the VEGF signaling pathway has become a valuable approach in the treatment of cancers. Guided by X-ray crystallography and molecular modeling, a series of 2-aminobenzimidazoles and 2-aminobenzoxazoles were identified as potent inhibitors of VEGFR-2 (KDR) in both enzymatic and HUVEC cellular proliferation assays. In this report we describe the synthesis and structure-activity relationship of a series of 2-aminobenzimidazoles and benzoxazoles, culminating in the identification of benzoxazole 22 as a potent and selective VEGFR-2 inhibitor displaying a good pharmacokinetic profile. Compound 22 demonstrated efficacy in both the murine matrigel model for vascular permeability (79% inhibition observed at 100 mg/kg) and the rat corneal angiogenesis model (ED(50) = 16.3 mg/kg).

  DOI：

  10.1021/jm070034i
• 作为产物：
  描述：

  2-甲硫基-4-氯嘧啶 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 4-(3,4-dinitro-phenoxy)-2-methylsulfonyl-pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Orally Active Benzimidazoles and Benzoxazoles as Vascular Endothelial Growth Factor-2 Receptor Tyrosine Kinase Inhibitors

  摘要：

  Inhibition of the VEGF signaling pathway has become a valuable approach in the treatment of cancers. Guided by X-ray crystallography and molecular modeling, a series of 2-aminobenzimidazoles and 2-aminobenzoxazoles were identified as potent inhibitors of VEGFR-2 (KDR) in both enzymatic and HUVEC cellular proliferation assays. In this report we describe the synthesis and structure-activity relationship of a series of 2-aminobenzimidazoles and benzoxazoles, culminating in the identification of benzoxazole 22 as a potent and selective VEGFR-2 inhibitor displaying a good pharmacokinetic profile. Compound 22 demonstrated efficacy in both the murine matrigel model for vascular permeability (79% inhibition observed at 100 mg/kg) and the rat corneal angiogenesis model (ED(50) = 16.3 mg/kg).

  DOI：

  10.1021/jm070034i

文献信息

• [EN] FUSED AZOLES SUCH AS 2,5-DISUBSTITUTED BENZIMIDAZOLES, BENZOXAZOLES AND BENZOTHIAZOLES AS KINASE INHIBITORS<br/>[FR] AZOLES FUSIONNES TELS QUE BENZIMIDAZOLES, BENZOXAZOLES ET BENZOTHIAZLES 2,5-DISUBSTITUES COMME INHIBITEURS DE KINASE
  申请人：AMGEN INC

  公开号：WO2004085425A1

  公开（公告）日：2004-10-07

  The invention relates to compounds of the formulae (I) to (III) wherein the substituents are as defined in the specification. These compounds have kinase inhibitory activity, such as VEGFR/KDR inhibitory activity. Accordingly, the compounds of the formulae (I) to (III) would be useful in the prevention and treatment of angiogenesis related disorders, ophthalmological conditions, proliferative diseases, inflammatory diseases, and other pathological conditions as described in the specification.

  这项发明涉及式(I)至(III)的化合物，其中取代基如规范中所定义。这些化合物具有激酶抑制活性，如VEGFR/KDR抑制活性。因此，式(I)至(III)的化合物在预防和治疗与血管生成相关的疾病、眼科疾病、增生性疾病、炎症性疾病以及规范中描述的其他病理状况中将会有用。
• Heterocyclic compounds and methods of use
  申请人：——

  公开号：US20040209892A1

  公开（公告）日：2004-10-21

  Selected compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis 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.

  选定的化合物对于预防和治疗血管生成介导的疾病等疾病有效。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、药物组合物以及预防和治疗癌症等疾病和其他疾病或病况的方法。本发明还涉及制备这些化合物的过程以及在这些过程中有用的中间体。
• Process for the preparation of alpha hydroxycarboxylic acid amides
  申请人：Zeller Martin

  公开号：US20050014950A1

  公开（公告）日：2005-01-20

  The invention concerns a novel process for the preparation of 2-phenyl-2-hydroxy-N-[2-(3-alkoxy-4-hydroxyphenyl)-ethyl]-acetamides of the formula (I), wherein R 1 is alkyl, R 2 and R 3 are each independently hydrogen or alkyl, and R 4 is optionally substituted aryl or optionally substituted heteroaryl, which process comprises reacting a 2-(3-alkoxy-4-hydroxyphenyl)-ethylamine of the formula (II), wherein R 1 R 2 and R 3 are as defined above with a α-hydoxycarboxylic acid ester of the formula (III) or a dioxolanone of the formula (III)a, wherein R 4 is as defined above, and R 5 , R 6 and R 7 independently of each other are lower alkyl. The compounds of formula (I) are important intermediates for a novel group of fungicides derived from mandelic acid amides.

  本发明涉及一种新型的制备2-苯基-2-羟基-N-[2-(3-烷氧基-4-羟基苯基)-乙基]-乙酰胺（式（I））的方法，其中R1为烷基，R2和R3各自独立地为氢或烷基，而R4为可选的取代芳基或可选的取代杂环芳基，该方法包括将式（II）的2-(3-烷氧基-4-羟基苯基)-乙胺与式（III）的α-羟基羧酸酯或式（III）a的二氧杂环戊酮反应，其中R1、R2和R3如上所定义，而R4如上所述，而R5、R6和R7各自独立地为低烷基。式（I）的化合物是从苦杏仁酸酰胺衍生的一类新型杀菌剂的重要中间体。
• Process the preparation of alpha-hydroxycarboxylic acid amides
  申请人：Syngenta Participations AG

  公开号：EP1526128A2

  公开（公告）日：2005-04-27

  The invention concerns a novel process for the preparation of 2-phenyl-2-hydroxy-N-[2-(3-alkoxy-4-hydroxyphenyl)-ethyl]-acetamides of the formula I wherein R1 is alkyl, R2, and R3 are each independently hydrogen or alkyl, and R4, is optionally substituted aryl or optionally substituted heteroaryl, which process comprises reacting a 2-(3-alkoxy-4-hydroxyphenyl)-ethylamine of the formula II wherein R1 R2 and R3 are as defined above with a α-hydoxycarboxylic acid ester of the formula III or a dioxolanone of the formula IIIa wherein R4 is as defined above, and R5, R6 and R7 independently of each other are lower alkyl. The compounds of formula I are important intermediates for a novel group of fungicides derived from mandelic acid amides.

  本发明涉及一种制备 2-苯基-2-羟基-N-[2-(3-烷氧基-4-羟基苯基)-乙基]-乙酰胺的新工艺，其式为 I 其中 R1 是烷基、 R2 和 R3 各自独立地为氢或烷基，以及 R4，是任选取代的芳基或任选取代的杂芳基，该工艺包括使式 II 的 2-(3-烷氧基-4-羟基苯基)-乙胺反应 其中 R1 R2 和 R3 如上定义，与式 III 的 α-氢氧羧酸酯或式 IIIa 的二氧戊环酮反应 其中 R4 如上定义，R5、R6 和 R7 相互独立地为低级烷基。 式 I 的化合物是由扁桃酸酰胺衍生的一类新型杀菌剂的重要中间体。
• PROCESS FOR THE PREPARATION OF ALPHA-HYDROXYCARBOXYLIC ACID AMIDES
  申请人：Syngenta Participations AG

  公开号：EP1444195B1

  公开（公告）日：2005-08-10