(+)-11-chloro-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzothiazepin-5-one | 149910-60-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: (+)-11-chloro-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzothiazepin-5-one
• 英文别名: (11S,11aS)-11-chloro-5-oxo-2,3,11,11a-tetrahydro-1H,5H-pyrrolo<2,1-c><1,4>benzothiazepine；(11S,11aS)-11-chloro-2,3,11,11a-tetrahydro-1H,5H-pyrrolo<2,1,c><1,4>benzothiazepin-5-one；(6S,6aS)-6-chloro-6a,7,8,9-tetrahydro-6H-pyrrolo[2,1-c][1,4]benzothiazepin-11-one
• CAS: 149910-60-1
• 化学式: C₁₂H₁₂ClNOS
• 分子量: 253.752
• InChiKey: YPFHOICWJRBLQR-GXSJLCMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  甲醇 、 (+)-11-chloro-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzothiazepin-5-one 在 silver(l) oxide 作用下， 以83%的产率得到(11R,11aS)-11-methoxy-2,3,11,11a-tetrahydro-1H,5H-pyrrolo<2,1,c><1,4>benzothiazepin-5-one
  参考文献：
  名称：

  Thioanalogues of anti-tumor antibiotics. II. Synthesis and preliminary in vitro cytotoxicity evaluation of tricyclic [1,4]benzothiazepine derivatives

  摘要：

  The synthesis of tricyclic [1,4]benzothiazepine derivatives starting from optically active cyclic amino acids and amino alcohols is described. The absolute configurations of the target compounds were assigned by X-ray and H-1-NMR analyses and by molecular modeling studies. The cytotoxic activity of the tricyclic derivatives was tested in vitro by growth inhibition assays using murine L1210 and human lymphoblastic CCRF-CEM leukemias. Compounds 5, 9, and 10 exhibited marked cytotoxic activity.

  DOI：

  10.1016/0223-5234(93)90136-3
• 作为产物：
  描述：

  (10R,11aS)-2,3,11,11a-tetrahydro-1H,5H-pyrrolo<2,1,c><1,4>benzothiazepin-5-one 10-oxide 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以80%的产率得到(+)-11-chloro-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzothiazepin-5-one
  参考文献：
  名称：

  Thioanalogues of anti-tumor antibiotics. II. Synthesis and preliminary in vitro cytotoxicity evaluation of tricyclic [1,4]benzothiazepine derivatives

  摘要：

  The synthesis of tricyclic [1,4]benzothiazepine derivatives starting from optically active cyclic amino acids and amino alcohols is described. The absolute configurations of the target compounds were assigned by X-ray and H-1-NMR analyses and by molecular modeling studies. The cytotoxic activity of the tricyclic derivatives was tested in vitro by growth inhibition assays using murine L1210 and human lymphoblastic CCRF-CEM leukemias. Compounds 5, 9, and 10 exhibited marked cytotoxic activity.

  DOI：

  10.1016/0223-5234(93)90136-3

文献信息

• Garofalo; Campiani; Fiorini, Il Farmaco, 1993, vol. 48, # 2, p. 275 - 283
  作者：Garofalo、Campiani、Fiorini、Nacci

  DOI：——

  日期：——
• Thiazolothiazepine Inhibitors of HIV-1 Integrase
  作者：Nouri Neamati、Jim A. Turpin、Heather E. Winslow、John L. Christensen、Karen Williamson、Ann Orr、William G. Rice、Yves Pommier、Antonio Garofalo、Antonella Brizzi、Giuseppe Campiani、Isabella Fiorini、Vito Nacci

  DOI：10.1021/jm990047z

  日期：1999.8.1

  A series of thiazolothiazepines were prepared and tested against purified human immunodeficiency virus type-1 integrase (HIV-1 IN) and viral replication. Structure-activity studies reveal that the compounds possessing the pentatomic moiety SC(O)CNC(O) with two carbonyl groups are in general more potent against purified IN than those containing only one carbonyl group. Substitution with electron-donating or -withdrawing groups did not enhance nor abolish potency against purified IN. By contrast, compounds with a naphthalene ring system showed enhanced potency, suggesting that a hydrophobic pocket in the IN active site might accommodate an aromatic system rather than a halogen. The position of sulfur in the thiazole ring appears important for potency against IN, as its replacement with an oxygen or carbon abolished activity. Further extension of the thiazole ring diminished potency. Compounds 1, 19, and 20 showed antiviral activity and inhibited IN within similar concentrations. These compounds inhibited IN when Mn2+ or Mg2+ was used as cofactor. None of these compounds showed detectable activities against HIV-1 reverse transcriptase, protease, virus attachment, or nucleocapsid protein zinc fingers. Therefore, thiazolothiazepines are potentially important lead compounds for development as inhibitors of IN and HIV replication.
• THIAZEPINE INHIBITORS OF HIV-1 INTEGRASE
  申请人：THE UNITED STATES GOVERNMENT as represented by THE DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：EP1187837B1

  公开（公告）日：2007-07-18
• Thioanalogues of anti-tumor antibiotics. II. Synthesis and preliminary in vitro cytotoxicity evaluation of tricyclic [1,4]benzothiazepine derivatives
  作者：A Garofalo、G Balconi、M Botta、F Corelli、M D'Incalci、G Fabrizi、I Fiorini、D Lamba、V Nacci

  DOI：10.1016/0223-5234(93)90136-3

  日期：1993.1

  The synthesis of tricyclic [1,4]benzothiazepine derivatives starting from optically active cyclic amino acids and amino alcohols is described. The absolute configurations of the target compounds were assigned by X-ray and H-1-NMR analyses and by molecular modeling studies. The cytotoxic activity of the tricyclic derivatives was tested in vitro by growth inhibition assays using murine L1210 and human lymphoblastic CCRF-CEM leukemias. Compounds 5, 9, and 10 exhibited marked cytotoxic activity.