(S)-6-(cyclopropylmethyl)-4,5,6,7-tetrahydro-5-methyl-9-nitroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one | 141114-47-8

• 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-(cyclopropylmethyl)-4,5,6,7-tetrahydro-5-methyl-9-nitroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one
• 英文别名: (+)-(S)-6-(Cyclopropylmethyl)-5-methyl-9-nitro-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one；(11S)-10-(cyclopropylmethyl)-11-methyl-6-nitro-1,3,10-triazatricyclo[6.4.1.04,13]trideca-4,6,8(13)-trien-2-one
• CAS: 141114-47-8
• 化学式: C₁₅H₁₈N₄O₃
• 分子量: 302.333
• InChiKey: SIUKSGPRWJQEGA-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  硫脲 、 (S)-6-(cyclopropylmethyl)-4,5,6,7-tetrahydro-5-methyl-9-nitroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one 在 三氯氧磷 作用下， 生成 (S)-7-Cyclopropylmethyl-8-methyl-4-nitro-6,7,8,9-tetrahydro-2H-2,7,9a-triaza-benzo[cd]azulene-1-thione
  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：

  Imidazo(4,5,1-jk)(1,4)benzodiazepin-2(1H)-one, 6-(cyclopropylmethyl)-4,5,6,7-tetrahydro-5-methyl-, (S)- 在 硝酸 作用下， 反应 0.5h， 生成 (S)-6-(cyclopropylmethyl)-4,5,6,7-tetrahydro-5-methyl-9-nitroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one 、 (+)-(S)-6-(cyclopropylmethyl)-5-methyl-8-nitro-4,5,6,7-tetrahydroimidazo<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 (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

• 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
• US6201119B1
  申请人：——

  公开号：US6201119B1

  公开（公告）日：2001-03-13
• [EN] ANTIVIRAL TETRAHYDROIMIDAZO[1,4]BENZODIAZEPIN-2-(THIO)ONES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1992000979A1

  公开（公告）日：1992-01-23

  (EN) Novel tetrahydroimidazo[1,4]benzodiazepin-2-(thio)ones of formula (I), the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein X is O or S; R1 is a radical of formula (a-1); (a-2); (a-3) or (a-4); R2 is hydrogen or C1-6¿alkyl; R3 is hydrogen or C¿1-6alkyl; R4 and R5 each independently are hydrogen, C1-6alkyl, halo, cyano, nitro, trifluoromethyl, hydroxy, C1-6alkyloxy, amino, mono- or di(C1-6alkyl)amino, C1-6alkylcarbonylamino or arylcarbonylamino, possessing antiviral activity. Compositions containing these compounds as active ingredient and methods of treating subjects suffering from viral infections by administering said compounds.(FR) Nouveaux tétrahydroimidazo[1,4]benzodiazépine-2-(thio)ones correspondant à la formule (I), leurs sels acides d'addition acceptables sur le plan pharmaceutique et leurs formes stéréochimiquement isomères, dans laquelle: X représente O ou S; R1 représente un radical de formule: (a-1), (a-2), (a-3) ou (a-4) R2 représente hydrogène ou C1-6alkyle; R3 représente hydrogène ou C1-6alkyle; R4 et R5 représentent indépendamment hydrogène, C1-6alkyle, halo, cyano, nitro, trifluorométhyle, hydroxy, C1-6alkyloxy, amino, mono- ou di(C1-6alkyle)amino, C1-6alkylcarbonylamino ou arylcarbonylamino ou arylcarbonylamino, possédant une efficacité antivirale. Compositions contenant lesdits composés comme constituants actifs et procédés de traitement de patients souffrant d'infections virales par administration desdits composés.
• 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
  作者：Winston Ho、Michael J. Kukla、Henry J. Breslin、Donald W. Ludovici、Philip P. Grous、Craig J. Diamond、Milton Miranda、James D. Rodgers、Chih Y. Ho

  DOI：10.1021/jm00005a006

  日期：1995.3

  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.