(+/-)-α-bromo-p-azidophenylacetic acid ethyl ester | 181304-18-7

• 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: (+/-)-α-bromo-p-azidophenylacetic acid ethyl ester
• 英文别名: Ethyl 2-(4-azidophenyl)-2-bromoacetate
• CAS: 181304-18-7
• 化学式: C₁₀H₁₀BrN₃O₂
• 分子量: 284.112
• InChiKey: YZCOXSKNKCUUDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  40.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-α-bromo-p-azidophenylacetic acid ethyl ester 在 N-甲基吗啉 、 tin(II) chloride dihdyrate 、 copper diacetate 、 sodium acetate 、 manganese triacetate 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 (Z)-5-(4-((S)-2-(((benzyloxy)carbonyl)amino)propanamido)phenyl)-2-((3-fluorophenyl)imino)-3-(furan-2-ylmethyl)-4-oxothiazolidin-5-yl acetate
  参考文献：
  名称：

  Inhibitors of HCV NS5A: From Iminothiazolidinones to Symmetrical Stilbenes

  摘要：

  The iminothiazolidinone BMS-858 (2) was identified as a specific inhibitor of HCV replication in a genotype 1b replicon assay via a high-throughput screening campaign. A more potent analogue, BMS-824 (18), was used in resistance mapping studies, which revealed that inhibitory activity was related to disrupting the function of the HCV nonstructural protein 5A. Despite the development of coherent and interpretable SAIL, it was subsequently discovered that in DMSO 18 underwent an oxidation and structural rearrangement to afford the thiohydantoin 47, a compound with reduced HCV inhibitory activity. However, HPLC bioassay fractionation studies performed after incubation of 18 in assay media led to the identification of fractions containing a dimeric species 48 that exhibited potent antiviral activity. Excision of the key elements hypothesized to be responsible for antiviral activity based on SAR observations reduced 48 to a simplified, symmetrical, pharmacophore realized most effectively with the stilbene 55, a compound that demonstrated potent inhibition of HCV in a genotype 1b replicon with an EC50 = 86 pM.

  DOI：

  10.1021/ml1002647
• 作为产物：
  描述：

  对氨基苯乙酸 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 硫酸 、 sodium nitrite 作用下， 以 四氯化碳 为溶剂， 反应 30.5h， 生成 (+/-)-α-bromo-p-azidophenylacetic acid ethyl ester
  参考文献：
  名称：

  吡咯并苯并氮杂庚因衍生物的合成，生物活性和SARs，是一类新的特定的“外围型”苯并二氮杂receptor受体配体。

  摘要：

  据报道，“外周型”苯二氮杂receptor受体（PBR）在许多生物学过程中起作用。为了提供新的受体配体，我们已经合成并测试了基于吡咯并苯并氮杂pine骨架的一系列PBR配体。这些新化合物中的几种被证明对PBR具有高亲和力和选择性配体，而苯并氮杂pine 17f和17j被认为是迄今为止对该受体最有效的配体。本文详述的SAR和分子模型研究描述了改善亲和力所需的许多结构特征。某些配体被用作“分子尺度”，以探究PBR裂隙中亲脂性口袋L1和L3的空间尺寸，并确定L1和L3的占领对亲和力的影响，而其他C-7修饰的类似物提供了有关与推定的受体位点H1进行氢键结合的专门信息。新的吡咯并苯并a庚因在大鼠皮层中进行了测试，该组织表达高密度的线粒体PBR，并通过[3H] PK 11195结合的位移测量，在低纳摩尔或亚纳摩尔范围内表现出IC50和Ki值。还发现最高亲和力配体的子集对大鼠肾上腺线粒体中的[3H] PK

  DOI：

  10.1021/jm960251b

文献信息

• Iminothiazolidinones as inhibitors of HCV replication
  申请人：Romine Lee Jeffrey

  公开号：US20050096364A1

  公开（公告）日：2005-05-05

  Compounds having the structure of formula I are described wherein R, R′, R 1 , R 2 , and R 3 are as defined in the specification. The compounds can inhibit hepatitis C virus (HCV) replication, and in particular the function of the HCV NS5A protein.

  本文描述了具有公式I结构的化合物，其中R，R'，R1，R2和R3的定义如规范中所述。这些化合物可以抑制丙型肝炎病毒（HCV）的复制，特别是HCV NS5A蛋白的功能。
• Combination pharmaceutical agents as inhibitors of HCV replication
  申请人：Colonno Richard

  公开号：US20050069522A1

  公开（公告）日：2005-03-31

  Disclosed are combination pharmaceutical agents for the treatment of an HCV infection comprising a compound effective to inhibit the function of the HCV NS5A protein and another compound having anti-HCV activity. Compounds which can inhibit the function of the NS5A protein having the structure of formula I are described wherein R, R′, R 1 , R 2 , and R 3 are as defined in the specification. The other compounds having anti-HCV activity are effective to inhibit the function of a target selected from the group consisting of HCV metalloprotease, HCV serine protease, HCV polymerase, HCV helicase, HCV NS4B protein, HCV entry, HCV assembly, HCV egress, HCV NS5A protein, IMPDH and a nucleoside analog for the treatment of an HCV infection.

  本发明涉及一种用于治疗HCV感染的联合药物组合，包括一种有效抑制HCV NS5A蛋白功能的化合物和具有抗HCV活性的另一种化合物。其中，可以抑制NS5A蛋白功能的化合物具有式I的结构，其中R、R'、R1、R2和R3的定义如规范中所述。具有抗HCV活性的其他化合物有效地抑制来自以下组的靶点的功能，包括HCV金属蛋白酶、HCV丝氨酸蛋白酶、HCV聚合酶、HCV解旋酶、HCV NS4B蛋白、HCV进入、HCV组装、HCV离子、HCV NS5A蛋白、IMPDH和核苷类似物，用于治疗HCV感染。
• US7183302B2
  申请人：——

  公开号：US7183302B2

  公开（公告）日：2007-02-27
• [EN] COMBINATION PHARMACEUTICAL AGENTS AS INHIBITORS OF HCV REPLICATION<br/>[FR] COMBINAISONS D'AGENTS PHARMACEUTIQUES EN TANT QU'INHIBITEURS DE REPLICATION HCV
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2004014313A2

  公开（公告）日：2004-02-19

  Disclosed are combination pharmaceutical agents for the treatment of an HCV infection comprising a compound effective to inhibit the function of the HCV NS5A protein and another compound having anti-HCV activity. Compounds which can inhibit the function of the NS5A protein having the structure of formula (I) are described; wherein R, R', R1, R2, and R3 are as defined in the specification. The other compounds having anti-HCV activity are effective to inhibit the function of a target selected from the group consisting of HCV metalloprotease, HCV serine protease, HCV polymerase, HCV helicase, HCV NS4B protein, HCV entry, HCV assembly, HCV egress, HCV NS5A protein, IMPDH and a nucleoside analog for the treatment of an HCV infection.
• [EN] IMINOTHIAZOLIDINONES AS INHIBITORS OF HCV REPLICATION<br/>[FR] IMINOTHIAZOLIDINONES S'UTILISANT COMME INHIBITEURS DE REPLICATION DU VHC
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2004014852A2

  公开（公告）日：2004-02-19

  Compounds having the structure of formula I are described (I) wherein R, R', R1, R2, and R3 are as defined in the specification. The compounds can inhibit hepatitis C virus (HCV) replication, and in particular the function of the HCV NS5A protein.