2,3,4,5-tetrahydro-3-methyl-9-nitro-4-(phenylmethyl)-1H-1,4-benzodiazepin-5-one | 126234-15-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 2,3,4,5-tetrahydro-3-methyl-9-nitro-4-(phenylmethyl)-1H-1,4-benzodiazepin-5-one
• 英文别名: 4-benzyl-3-methyl-9-nitro-2,3-dihydro-1H-1,4-benzodiazepin-5-one
• CAS: 126234-15-9
• 化学式: C₁₇H₁₇N₃O₃
• 分子量: 311.34
• InChiKey: PFAXDIBIYXARJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  78.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,3,4,5-tetrahydro-3-methyl-9-nitro-4-(phenylmethyl)-1H-1,4-benzodiazepin-5-one 在 palladium on activated charcoal lithium aluminium tetrahydride 、 硫酸 、 氢气 、 1-羟基苯并三唑 作用下， 以 四氢呋喃 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 42.0 ℃ 、413.69 kPa 条件下， 反应 32.67h， 生成 6-Acetyl-4,5,6,7-tetrahydro-5-methylimidazo(4,5,1-jk)(1,4)benzodiazepin-2(1H)-one
  参考文献：
  名称：

  Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one (TIBO) derivatives

  摘要：

  A series of 6-substituted 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-ones (9) have been synthesized and tested for their ability to inhibit the replication of the HIV-1 virus in MT-4 cells. Two synthetic methods are described, one of which allows the synthesis of single enantiomers of the final products. A structure-activity study was done within the series of compounds to determine the optimum group for the 6-position substitution and to determine whether the activity was enantiospecific at the 5-position, which was substituted with a methyl group. The best analogue, 9jj, inhibited HIV-1 with an IC50 of 4-mu-M, which is comparable to the activity level of DDI, a 2',3'-dideoxynucleoside-type structure undergoing clinical trials as an anti-AIDS therapy.

  DOI：

  10.1021/jm00106a040
• 作为产物：
  描述：

  2-溴-3-硝基苯甲酸甲酯 在 2-羟基吡啶 、 sodium carbonate 作用下， 以 xylene 、 正丁醇 为溶剂， 反应 20.5h， 生成 2,3,4,5-tetrahydro-3-methyl-9-nitro-4-(phenylmethyl)-1H-1,4-benzodiazepin-5-one
  参考文献：
  名称：

  Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one (TIBO) derivatives

  摘要：

  A series of 6-substituted 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-ones (9) have been synthesized and tested for their ability to inhibit the replication of the HIV-1 virus in MT-4 cells. Two synthetic methods are described, one of which allows the synthesis of single enantiomers of the final products. A structure-activity study was done within the series of compounds to determine the optimum group for the 6-position substitution and to determine whether the activity was enantiospecific at the 5-position, which was substituted with a methyl group. The best analogue, 9jj, inhibited HIV-1 with an IC50 of 4-mu-M, which is comparable to the activity level of DDI, a 2',3'-dideoxynucleoside-type structure undergoing clinical trials as an anti-AIDS therapy.

  DOI：

  10.1021/jm00106a040

文献信息

• Antiviral tetrahydroimidazo (1,4) benzodiazepin-2-ones
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0336466A1

  公开（公告）日：1989-10-11

  Novel antiviral tetrahydroimidazo[1,4]benzodiazepin-2-ones of formula a pharmaceutically acceptable acid addition salt or a stereochemically isomeric form thereof, wherein R¹ is hydrogen, C₁₋₈alkyl, C₃₋₆alkenyl, C₃₋₆alkynyl, C₁₋₆alkylcarbonyl, C₃₋₆cycloalkyl, or substituted C₁₋₆alkyl; R² is hydrogen, C₁₋₆alkyl or C₃₋₆alkenyl R³ is hydrogen or C₁₋₆alkyl; R⁴ is hydrogen; substituted C₁₋₆alkyl; C₁₋₆alkylcarbonyl; C₃₋₆alkenyl; C₃₋₆cycloalkyl; C₅₋₆cycloalkenyl; R⁵ is hydrogen, C₁₋₆alkyl or halo; and aryl is optionally substituted phenyl; pharmaceutical compositions containing these compounds as active ingredient; processes for preparing said compounds and compositions.

  新型抗病毒四氢咪唑并[1,4]苯并二氮杂卓-2-酮，其式为药学上可接受的酸加成盐或其立体化学异构体、 其中 R¹ 是氢、C₁₋₈烷基、C₃₋₆烯基、C₁₋₆炔基、C₁₋₆烃基、C₃₋₆ 环烷基或取代的 C₁₋₆烷基； R² 是氢、C₁₋₆烷基或 C₃₋₆ 烷基 R³ 是氢或 C₁₋₆ 烷基； R⁴是氢；取代的C₁₋₆烷基；C₃₋₆烷基羰基；C₃₋₆环烷基；C₅₋₆环烷基；R⁵是氢、C₁₋₆烷基或卤素； 芳基是任选取代的苯基；含有这些化合物作为活性成分的药物组合物；制备所述化合物和组合物的工艺。
• Antiviral tetrahydroimidazo[1,4]benzodiazepin-2-thiones
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0384522A1

  公开（公告）日：1990-08-29

  Novel tetrahydroimidazo[1,4]benzodiazepin-2-thiones of formula wherein R¹ is C₁₋₆alkyl, C₃₋₆alkenyl, C₃₋₆alkynyl, C₃₋₆cycloalkyl, or C₁₋₆alkyl substituted with aryl or with C₃₋₆cycloalkyl; R², R³ are hydrogen or C₁₋₆alkyl; R⁴, R⁵ are hydrogen, C₁₋₆alkyl, halo, cyano, nitro, trifluoromethyl, hydroxy, C₁₋₆alkyloxy, amino or mono-or di(C₁₋₆alkylamino); aryl is optionally substituted phenyl; pharmaceutical compositions containing these compounds as active ingredient; processes for preparing said compounds and compositions.

  式中的新型四氢咪唑并[1,4]苯并二氮杂卓-2-硫酮 其中 R¹ 是 C₁₋₆烷基、C₃₋₆ 烷基、C₃₋₆ 炔基、C₁₋₆烷基或被芳基或 C₃₋₆cycloalkyl 取代的 C₁₋₆烷基； R²、R³是氢或 C₁₋₆烷基； R⁴、R⁵是氢、C₁₋₆烷基、卤代、氰基、硝基、三氟甲基、羟基、C₁₋₆烷氧基、氨基或单或二(C₁₋₆烷基氨基)； 芳基是任选取代的苯基； 含有这些化合物作为活性成分的药物组合物；制备所述化合物和组合物的工艺。
• KUKLA, MICHAEL J.;BRESLIN, HENRY J.;PAUWELS, RUDI;FEDDE, CYNTHIA L.;MIRAN+, J. MED. CHEM., 34,(1991) N, C. 746-751
  作者：KUKLA, MICHAEL J.、BRESLIN, HENRY J.、PAUWELS, RUDI、FEDDE, CYNTHIA L.、MIRAN+

  DOI：——

  日期：——
• ANTIVIRAL TETRAHYDROIMIDAZO 1,4]BENZODIAZEPIN-2-(THIO)ONES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0538297B9

  公开（公告）日：2002-10-16
• US5270464A
  申请人：——

  公开号：US5270464A

  公开（公告）日：1993-12-14