(R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(4-iodo-3-methoxyphenyl)ethane-1,2-dione | 1173176-92-5

• 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-iodo-3-methoxyphenyl)ethane-1,2-dione
• CAS: 1173176-92-5
• 化学式: C₂₁H₂₁IN₂O₄
• 分子量: 492.313
• InChiKey: YRUQBVGIRKXFRP-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.86
• 重原子数：
  28.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  66.92
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(4-iodo-3-methoxyphenyl)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 1,4-二氧六环 为溶剂， 反应 18.0h， 以10 mg的产率得到(R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(3-methoxy-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：

  ((R)-4-benzoyl-2-methylpiperazin-1-yl)acetonitrile 、 4-碘-3-甲氧基苯甲酸甲酯 在 sodium hexamethyldisilazane 、 sodium hypochlorite 作用下， 以 四氢呋喃 、 水 为溶剂， 以25%的产率得到(R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(4-iodo-3-methoxyphenyl)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