(R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(2-methoxy-4-(1H-pyrazol-5-yl)phenyl)ethane-1,2-dione | 948989-88-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(2-methoxy-4-(1H-pyrazol-5-yl)phenyl)ethane-1,2-dione
• 英文别名: 1-[(1S,2R,4R)-4-benzoyl-2-methyl-piperazin-1-yl]-2-[2-methoxy-4-(1H-pyrazol-3-yl)phenyl]ethane-1,2-dione；1-[(2R)-4-benzoyl-2-methylpiperazin-1-yl]-2-[2-methoxy-4-(1H-pyrazol-5-yl)phenyl]ethane-1,2-dione
• CAS: 948989-88-6
• 化学式: C₂₄H₂₄N₄O₄
• 分子量: 432.479
• InChiKey: RVYWLAFJFCKXAG-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  95.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1H-吡唑-3-硼酸 、 1-(4-benzoyl-2(R)-methylpiperazin-1-yl)-2-(4-bromo-2-methoxyphenyl)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36 mg的产率得到(R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(2-methoxy-4-(1H-pyrazol-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

文献信息

• Piperazine and piperidine biaryl derivatives
  申请人：Lu Jian Rong

  公开号：US20070259879A1

  公开（公告）日：2007-11-08

  This invention relates to piperazine and piperidine biaryl compounds of Formula (I): or a pharmaceutically acceptable prodrug, salt, polymorph, solvate, enantiomer, diastereomer, racemate, mixture of stereoisomers thereof, or derivative thereof; and to processes for preparing the compounds or pharmaceutical compositions containing the same. The compounds and pharmaceutical compositions of the present invention are provided for use in the treatment of HIV infection and/or AIDS.

  本发明涉及公式（I）的哌嗪和哌啶双芳基化合物： 或其药物可接受的前药、盐、多晶形、溶剂化物、对映体、非对映体、外消旋体、其立体异构体混合物或衍生物；以及用于制备化合物或含有相同化合物的制药组合物的过程。本发明的化合物和制剂用于治疗HIV感染和/或艾滋病。
• Heterobiaryl Human Immunodeficiency Virus Entry Inhibitors
  作者：Rong-Jian Lu、John A. Tucker、Jason Pickens、You-An Ma、Tatiana Zinevitch、Olga Kirichenko、Vitalii Konoplev、Svetlana Kuznetsova、Sergey Sviridov、Enugurthi Brahmachary、Alisher Khasanov、Charles Mikel、Yang Yang、Changhui Liu、Jian Wang、Stephanie Freel、Shelly Fisher、Alana Sullivan、Jiying Zhou、Sherry Stanfield-Oakley、Brian Baker、Jeff Sailstad、Michael Greenberg、Dani Bolognesi、Brian Bray、Barney Koszalka、Peter Jeffs、Cynthia Jeffries、Alexander Chucholowski、Connie Sexton

  DOI：10.1021/jm900330x

  日期：2009.7.23

  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.