(+/-)-2,3,11,11a-tetrahydro-11-hydroxy-11-phenyl-1H,5H-pyrrolo[2,1-c][1,4]benzothiazepin-5-one

• 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: (+/-)-2,3,11,11a-tetrahydro-11-hydroxy-11-phenyl-1H,5H-pyrrolo[2,1-c][1,4]benzothiazepin-5-one
• 英文别名: 6-Hydroxy-6-phenyl-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzothiazepin-11-one
• 化学式: C₁₈H₁₇NO₂S
• 分子量: 311.404
• InChiKey: NOBKWXHTKUURTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  苯基溴化镁 、 (+/-)-1,2,3,11a-tetrahydro-5H,11H-pyrrolo[2,1-c][1,4]benzothiazepine-5,11-dione 在 水 、 氯化铵 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 0.5h， 以59%的产率得到(+/-)-2,3,11,11a-tetrahydro-11-hydroxy-11-phenyl-1H,5H-pyrrolo[2,1-c][1,4]benzothiazepin-5-one
  参考文献：
  名称：

  Thiazepine inhibitors of HIV-1 integrase

  摘要：

  本发明公开了非儿茶酚化合物，如噻唑并噻二嗪类化合物及其类似物和衍生物，这些化合物是抗整合酶抑制剂。这些化合物可用作治疗HIV疾病的药物，包括化合物(I)、(II)、(III)或其药学上可接受的盐，其中A为噻唑、苯、萘、吡啶、嘧啶、吡嗪或喹啉；R为H、卤素、较低烷基、较低烷氧基、NO2、较低酯或羧酸中的一个或多个；X—Y为CH2—S、S—CH2、CH2—O、CH2—S(O)、S(O)—CH2、CH2—CH2、CH2—CH2—CH2或CH2—CH2—CH2—CH2；R4为H或羟基；R5为H、苯基或烷基胺基；W为S或O；R6为H、取代或未取代的烷基或胺基；Z为S、O、CH2、CH2CH2或C═O。

  公开号：

  US07015212B1

文献信息

• 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
• US7015212B1
  申请人：——

  公开号：US7015212B1

  公开（公告）日：2006-03-21
• Thiazepine inhibitors of HIV-1 integrase
  申请人：The United States of America as represented by the Department of Health and Human Services

  公开号：US07015212B1

  公开（公告）日：2006-03-21

  The present invention discloses non-catechol compounds, such as thiazolothiazepines, and analogs and derivatives thereof, which are anti-integrase inhibitors. The compounds, which are useful as treatments for HIV disease, include compounds (I), (II), (III), or pharmaceutically acceptable salts thereof wherein A is thiazole, benzene, naphthalene, pyridine, pyrimidine, pyrazine, or quinoline; R is one or more of H, halogen, lower alkyl, lower alkoxy, NO2, lower ester or carboxylic acid; X—Y is CH2—S, S—CH2, CH2—O, CH2—S(O). S(O)—CH2, CH2—CH2, CH2—CH2—CH2, or CH2—CH2—CH2—CH2; R4 is H or hydroxy; R5 is H, phenyl, or alkylamine; W is S or O; and R6 is H, substituted or unsubstituted alkyl or amine; and Z is S, O, CH2, CH2CH2, or C═O.

  本发明公开了非儿茶酚化合物，如噻唑并噻二嗪类化合物及其类似物和衍生物，这些化合物是抗整合酶抑制剂。这些化合物可用作治疗HIV疾病的药物，包括化合物(I)、(II)、(III)或其药学上可接受的盐，其中A为噻唑、苯、萘、吡啶、嘧啶、吡嗪或喹啉；R为H、卤素、较低烷基、较低烷氧基、NO2、较低酯或羧酸中的一个或多个；X—Y为CH2—S、S—CH2、CH2—O、CH2—S(O)、S(O)—CH2、CH2—CH2、CH2—CH2—CH2或CH2—CH2—CH2—CH2；R4为H或羟基；R5为H、苯基或烷基胺基；W为S或O；R6为H、取代或未取代的烷基或胺基；Z为S、O、CH2、CH2CH2或C═O。