2-[(2,6-二氯-3-硝基苄基)氨基]丙酰胺 | 141114-44-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 2-[(2,6-二氯-3-硝基苄基)氨基]丙酰胺
• 英文名称: 2-<(2,6-dichloro-3-nitrobenzyl)amino>propionamide
• 英文别名: (S)-2-[[(2,6-dichloro-3-nitrophenyl)methyl]amino]propanamide；(2S)-2-[(2,6-dichloro-3-nitrophenyl)methylamino]propanamide
• CAS: 141114-44-5
• 化学式: C₁₀H₁₁Cl₂N₃O₃
• 分子量: 292.122
• InChiKey: LKOYOQATGVPGFU-YFKPBYRVSA-N

物化性质

• 沸点：
  478.8±45.0 °C(Predicted)
• 密度：
  1.453±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(2,6-二氯-3-硝基苄基)氨基]丙酰胺 在 lithium aluminium tetrahydride 、 硼烷四氢呋喃络合物 、 sodium acetate 、 sodium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 168.5h， 生成 (+)-(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-硝基苯甲醛 、 L-丙氨酰胺盐酸盐 在 sodium acetate 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 0.75h， 以71%的产率得到2-[(2,6-二氯-3-硝基苄基)氨基]丙酰胺
  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

文献信息

• 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##
• Antiretroviral tetrahydroimidazo[1,4]benzodiazepin-2-(thi)ones
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05371079A1

  公开（公告）日：1994-12-06

  The compounds are of the class of tetrahydroimidazo[1,4]benzodiazepin-2-(thi)ones possessing antiretroviral, especially anti-HIV-1, activity. An illustrative compound is (+)-S-4,5,6,7-tetrahydro-9-chloro-5-methyl-6-(3-methyl-2-butenyl)imidazo[4 ,5,1-jk][1,4]benzodiazepine-2(1H)-thione. These compounds are represented by the formula: ##STR1## The application also discloses compositions containing these compounds as active ingredients and methods of treating subjects suffering from retroviral infections by administering said compounds.

  这些化合物属于四氢咪唑[1,4]苯并二氮平-2-(硫)酮类，具有抗逆转录病毒，尤其是抗HIV-1的活性。一个说明性的化合物是(+)-S-4,5,6,7-四氢-9-氯-5-甲基-6-(3-甲基-2-丁烯基)咪唑[4,5,1-jk][1,4]苯并二氮平-2(1H)-硫酮。这些化合物由以下式子表示：##STR1## 该申请还披露了包含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逆转录病毒感染的受试者的方法。
• 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
• US5371079A
  申请人：——

  公开号：US5371079A

  公开（公告）日：1994-12-06