1-((R)-4-benzoyl-2-methylpiperazin-1-yl)-2-[2-benzyloxy-4-bromophenyl]ethane-1,2-dione | 1173176-94-7

• 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: 1-((R)-4-benzoyl-2-methylpiperazin-1-yl)-2-[2-benzyloxy-4-bromophenyl]ethane-1,2-dione
• 英文别名: 1-[(2R)-4-benzoyl-2-methylpiperazin-1-yl]-2-(4-bromo-2-phenylmethoxyphenyl)ethane-1,2-dione
• CAS: 1173176-94-7
• 化学式: C₂₇H₂₅BrN₂O₄
• 分子量: 521.41
• InChiKey: APCFIVZGGGPNNK-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1H-吡唑-3-硼酸 、 1-((R)-4-benzoyl-2-methylpiperazin-1-yl)-2-[2-benzyloxy-4-bromophenyl]ethane-1,2-dione 在 四(三苯基膦)钯 、 四丁基溴化铵 、 sodium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 16.0h， 以49%的产率得到1-((R)-4-benzoyl-2-methylpiperazin-1-yl)-2-[2-benzyloxy-4-(1H-pyrazol-3-yl)phenyl]ethane-1,2-dione
  参考文献：
  名称：

  Heterobiaryl Human Immunodeficiency Virus Entry Inhibitors

  摘要：

  Previously disclosed HIV (human immunodeficiency virus) attachment inhibitors, exemplified by BMS 806 (formally BMS378806, 1), are characterized by a substituted indole or azaindole ring linked to a benzoylpiperazine via a ketoamide or sulfonamide group. In the present report, we describe the discovery of a novel series of potent HIV entry inhibitors in which the indole or azaindole ring of previous inhibitors is replaced by a heterobiaryl group. Several of these analogues exhibited IC(50) values of less than 5 nM in a pseudotyped antiviral assay, and compound 13k was demonstrated to exhibit potency and selectivity similar to those of I against a panel of clinical viral isolates. Moreover, current structure-activity relationship studies of these novel biaryl gp120 inhibitors revealed that around the biaryl, a fine crevice might exist in the gp120 binding site. Taken in sum, these data reveal a hitherto unsuspected flexibility in the structure-activity relationships for these inhibitors and suggest new avenues for exploration and gp120 inhibitor design.

  DOI：

  10.1021/jm900330x
• 作为产物：
  描述：

  1-((R)-4-benzoyl-2-methylpiperazin-1-yl)-2-(4-bromo-2-fluorophenyl)ethane-1,2-dione 、 苯甲醇 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以62%的产率得到1-((R)-4-benzoyl-2-methylpiperazin-1-yl)-2-[2-benzyloxy-4-bromophenyl]ethane-1,2-dione
  参考文献：
  名称：

  Heterobiaryl Human Immunodeficiency Virus Entry Inhibitors

  摘要：

  Previously disclosed HIV (human immunodeficiency virus) attachment inhibitors, exemplified by BMS 806 (formally BMS378806, 1), are characterized by a substituted indole or azaindole ring linked to a benzoylpiperazine via a ketoamide or sulfonamide group. In the present report, we describe the discovery of a novel series of potent HIV entry inhibitors in which the indole or azaindole ring of previous inhibitors is replaced by a heterobiaryl group. Several of these analogues exhibited IC(50) values of less than 5 nM in a pseudotyped antiviral assay, and compound 13k was demonstrated to exhibit potency and selectivity similar to those of I against a panel of clinical viral isolates. Moreover, current structure-activity relationship studies of these novel biaryl gp120 inhibitors revealed that around the biaryl, a fine crevice might exist in the gp120 binding site. Taken in sum, these data reveal a hitherto unsuspected flexibility in the structure-activity relationships for these inhibitors and suggest new avenues for exploration and gp120 inhibitor design.

  DOI：

  10.1021/jm900330x