(R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(4-bromo-3-fluorophenyl)ethane-1,2-dione | 1173177-00-8

• 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: (R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(4-bromo-3-fluorophenyl)ethane-1,2-dione
• 英文别名: 1-[(2R)-4-benzoyl-2-methylpiperazin-1-yl]-2-(4-bromo-3-fluorophenyl)ethane-1,2-dione
• CAS: 1173177-00-8
• 化学式: C₂₀H₁₈BrFN₂O₃
• 分子量: 433.277
• InChiKey: SHPRLZGSUXXIJR-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  57.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(4-bromo-3-fluorophenyl)ethane-1,2-dione 、 三丁基-(3-甲基-1,2-恶唑-5-基)锡烷 在 bis-triphenylphosphine-palladium(II) chloride 作用下， 以 四氢呋喃 为溶剂， 生成 (R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(3-fluoro-4-(3-methylisoxazol-5-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：

  4-溴-3-氟苯甲酸甲酯 、 ((R)-4-benzoyl-2-methylpiperazin-1-yl)acetonitrile 在 sodium hexamethyldisilazane 、 sodium hypochlorite 作用下， 以 四氢呋喃 、 水 为溶剂， 以31%的产率得到(R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(4-bromo-3-fluorophenyl)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