(S)-6-chloro-2,3,4,5-tetrahydro-3-methyl-4-(3-methyl-2-butenyl)-1H-1,4-benzodiazepin-9-amine | 149976-82-9

• 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: (S)-6-chloro-2,3,4,5-tetrahydro-3-methyl-4-(3-methyl-2-butenyl)-1H-1,4-benzodiazepin-9-amine
• 英文别名: (3S)-6-chloro-3-methyl-4-(3-methylbut-2-enyl)-1,2,3,5-tetrahydro-1,4-benzodiazepin-9-amine
• CAS: 149976-82-9
• 化学式: C₁₅H₂₂ClN₃
• 分子量: 279.813
• InChiKey: JBUAWSUJDJDRPE-NSHDSACASA-N

物化性质

• 沸点：
  411.9±45.0 °C(Predicted)
• 密度：
  1.093±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  41.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-6-chloro-2,3,4,5-tetrahydro-3-methyl-4-(3-methyl-2-butenyl)-1H-1,4-benzodiazepin-9-amine 、 N,N'-硫羰基二咪唑 以 四氢呋喃 为溶剂， 反应 0.5h， 以54%的产率得到(+)-(S)-4,5,6,7-四氢-8-氯-5-甲基-6-(3-甲基-2-丁烯基)咪唑并[4,5,1-jk][1,4]苯并二氮杂卓-2-(1H)-硫酮
  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 (TlBO) Derivatives. 4

  摘要：

  In previous papers, we have described the discovery of a new series of compounds, 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-ones, TlBO (1 and 1a), with potent anti-HIV-1 activity and the synthesis of analogues to better define the structure-activity relationships (SAR) in terms of changes in substituents at the N-6 position and variations of the five-membered urea ring as well as the seven-membered diazepine ring. This paper describes the synthesis of TlBO analogues with various substituents on the aromatic ring and their SAR in terms of anti-HIV-1 properties. Substituents on the 8-position furnished the most rewarding results and gave a large improvement in potency versus the parent compound. These included halogen, thiomethyl, and methyl. Analogues like 8-cyano, -methoxy, and -acetylene were equipotent, while 8-amino, -acetylamino, -dimethylamino, and -nitro were inactive (Table 1). Substituents at the 9-position tended to have little effect on activity, and 10-substituents decreaseed activity. The 8-chloro compound 6a with IC50 = 0.0043 mu M is currently under clinical development.

  DOI：

  10.1021/jm00005a006
• 作为产物：
  描述：

  2,6-二氯-3-硝基苯甲酸 在 palladium on activated charcoal 草酰氯 、 dimethyl sulfide borane 、 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 51.83h， 生成 (S)-6-chloro-2,3,4,5-tetrahydro-3-methyl-4-(3-methyl-2-butenyl)-1H-1,4-benzodiazepin-9-amine
  参考文献：
  名称：

  Regioselectivity in intramolecular nucleophilic aromatic substitution. Synthesis of the potent anti HIV-I 8-halo TIBO analogs

  摘要：

  Regioselective intramolecular nucleophilic substitution of 2,6-dihalo-3-nitrobenzyl diamines 2b and 2c gave benzodiazepines 3. These intermediates are useful in the preparation of the 8-halo TIBO derivatives 1, inhibitors of HIV-I replication in cell culture.

  DOI：

  10.1021/jo00027a019

文献信息

• Process for preparing enantiomerically pure
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05463049A1

  公开（公告）日：1995-10-31

  Process for preparing enantiomerically pure imidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-thiones of formula ##STR1## starting from 2,6-dihalo-3-nitrobenzyl derivatives (II) and suitably N-protected 1,2-diaminopropanes (III) ##STR2## Novel enantiomerically pure intermediates of formula (III) and (IV) prepared in the course of the present process.

  制备具有公式##STR1##的立体纯的咪唑[4,5,1-jk][1,4]苯并二氮杂卓-2(1H)-硫酮的方法，从2,6-二卤代-3-硝基苄基衍生物(II)和适当的N-保护的1,2-二氨基丙烷(III)##STR2##开始。本过程中制备的新颖立体纯中间体为公式(III)和(IV)。
• Anti-HIV-1 tetrahydroimidazo[1,4]benzodiazepin-2-(thi) ones
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05270464A1

  公开（公告）日：1993-12-14

  Novel tetrahydroimidazo[1,4]benzodiazepin-2-(thi)ones possessing anti-HIV-1 activity, compositions containing these compounds as active ingredients, and methods of treating subjects suffering from HIV-1 infection by administering these compounds. The compounds have the basic structure shown in Formula (I): ##STR1##

  新型四氢咪唑并[1,4]苯二氮杂环己烷-2-(硫)酮具有抗HIV-1活性，含有这些化合物作为活性成分的组合物，以及通过给予这些化合物治疗患有HIV-1感染的受试者的方法。这些化合物具有在式(I)中显示的基本结构：##STR1##
• Process for preparing enantiomerically pure imidazo[4,5,1-jk]-[1,4]-benzodiazepin-2(1H)-thiones
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0534539A1

  公开（公告）日：1993-03-31

  Process for preparing enantiomerically pure imidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-thiones of formula starting from 2,6-dihalo-3-nitrobenzyl derivatives (II) and suitably N-protected 1,2-diaminopropanes (III) Novel enantiomerically pure intermediates of formula (III) and (IV) prepared in the course of the present process.

  式中对映体纯咪唑并[4,5,1-jk][1,4]苯并二氮杂卓-2(1H)-硫酮的制备工艺 从 2,6-二卤-3-硝基苄基衍生物（II）和适当的 N 保护的 1,2-二氨基丙烷（III）开始 在本工艺过程中制备的式 (III) 和 (IV) 的新型对映体纯中间体。
• PROCESS FOR PREPARING ENANTIOMERICALLY PURE IMIDAZO 4,5,1-jk] 1,4]-BENZODIAZEPIN-2(1H -)-THIONES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0605499B1

  公开（公告）日：1997-11-12
• US5270464A
  申请人：——

  公开号：US5270464A

  公开（公告）日：1993-12-14