(S)-2,3,4,5-tetrahydro-3-methyl-1H-<1,4>benzodiazepine-9-amine | 163120-52-3

• 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)-2,3,4,5-tetrahydro-3-methyl-1H-<1,4>benzodiazepine-9-amine
• 英文别名: (S)-3-Methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-9-amine；(3S)-3-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-9-amine
• CAS: 163120-52-3
• 化学式: C₁₀H₁₅N₃
• 分子量: 177.249
• InChiKey: RKABKHMTQZJQDF-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  50.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2,3,4,5-tetrahydro-3-methyl-1H-<1,4>benzodiazepine-9-amine 在 N-甲基吗啉 、 sodium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 23.75h， 生成 (+)-(S)-4,5,6,7-Tetrahydro-5-methyl-6-(2-propenyl)-imidazo-(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：

  (-)-methyl (S)-2-<(2-amino-3-nitrobenzoyl)amino>propanoate 在 palladium on activated charcoal lithium aluminium tetrahydride 、 氢气 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 100.0~200.0 ℃ 、310.27 kPa 条件下， 反应 49.67h， 生成 (S)-2,3,4,5-tetrahydro-3-methyl-1H-<1,4>benzodiazepine-9-amine
  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

• Imidazol-4-ylpiperidine derivatives, their preparation and their
  申请人：Synthelabo

  公开号：US05589476A1

  公开（公告）日：1996-12-31

  A compound of formula (I): ##STR1## in which R.sub.1 represents a hydrogen atom or a straight or branched (C.sub.1 -C.sub.4)alkyl group; and A represents a 5,6-dihydro-4H-imidazo[4,5,1-ij]quinol-2-yl group, a 4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yl group, a 4-methyl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yl group, a 4-phenyl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yl group, a 4-phenylmethyl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yl group, a 5-methyl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yl group, a 5,6-dihydro-4H-imidazo[1,5,4-de]quinoxalin-2-yl group, a 6-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinol-2-yl group, or a 5-methyl-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2-yl group which may be unsubstituted or substituted in the 6-position by a phenylmethyl group; or an addition salt thereof with a pharmaceutically acceptable acid.

  式（I）的化合物：##STR1##其中R.sub.1代表氢原子或直链或支链（C.sub.1-C.sub.4）烷基基团；A代表5,6-二氢-4H-咪唑并[4,5,1-ij]喹啉-2-基基团，4,5-二氢咪唑并[1,5,4-de][1,4]苯并噁唑-2-基基团，4-甲基-4,5-二氢咪唑并[1,5,4-de][1,4]苯并噁唑-2-基基团，4-苯基-4,5-二氢咪唑并[1,5,4-de][1,4]苯并噁唑-2-基基团，4-苯甲基-4,5-二氢咪唑并[1,5,4-de][1,4]苯并噁唑-2-基基团，5-甲基-4,5-二氢咪唑并[1,5,4-de][1,4]苯并噁唑-2-基基团，5,6-二氢-4H-咪唑并[1,5,4-de]喹啉-2-基基团，6-氧代-5,6-二氢-4H-咪唑并[4,5,1-ij]喹啉-2-基基团，或5-甲基-4,5,6,7-四氢咪唑并[4,5,1-jk][1,4]苯并二氮杂环-2-基基团，该基团可以在6位被苯甲基基团取代或未取代；或其与药学上可接受的酸形成的盐。
• Dérivés d'imidazol-4-yl-pipéridine, leur préparation et leur application en thérapeutique
  申请人：SYNTHELABO

  公开号：EP0646583A1

  公开（公告）日：1995-04-05

  Composés répondant à la formule (I) dans laquelle R₁ représente soit un atome d'hydrogène, soit un groupe (C₁-C₆)alkyle droit ou ramifié et A représente soit un groupe 5,6-dihydro-4H-imidazo[4,5,1-ij] quinoléin-2-yle, soit un groupe 4,5-dihydroimidazo[1,5,4-de] [1,4]benzoxazin-2-yle, soit un groupe 4-méthyl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yle, soit un groupe 4-phényl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yle, soit un groupe 4-(phénylméthyl)-4,5-dihydroimidazo[1,5,4-de][1,4] benzoxazin-2-yle, soit un groupe 5-méthyl-4,5-dihydroimidazo[1,5,4-de] [1,4]benzoxazin-2-yle, soit un groupe 5,6-dihydro-4H-imidazo[1,5,4-de]quinazolin-2-yle, soit un groupe 6-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoléin-2-yle, soit un groupe 5-méthyl-4,5,6,7-tétrahydroimidazo[4,5,1-jk][1,4] benzodiazépin-2-yle éventuellement substitué en 6 par un groupe phénylméthyle ainsi que leurs sels d'additions aux acides pharmaceutiquement acceptables. Les composés de l'invention sont des ligands des récepteurs sérotoninergiques de types 5-HT₃ et 5-HT₄.

  与式（I）对应的化合物 其中 R₁ 代表氢原子或直链或支链（C₁-C₆）烷基，以及 A 代表 5,6-二氢-4H-咪唑并[4,5,1-ij]喹啉-2-基团，或 4,5-二氢咪唑并[1,5,4-de][1,4]苯并恶嗪-2-基团，或 4-甲基-4,5-二氢咪唑并[1,5,4-de][1、4]苯并恶嗪-2-基，或 4-苯基-4,5-二氢咪唑并[1,5,4-de][1,4]苯并恶嗪-2-基，或 4-(苯基甲基)-4,5-二氢咪唑并[1,5,4-de][1,4]苯并恶嗪-2-基，或 5-甲基-4、5-甲基-4,5-二氢咪唑并[1,5,4-de][1,4]苯并恶嗪-2-基，或 5-甲基-4,5-二氢咪唑并[1,5,4-de]喹唑啉-2-基，或 6-氧代-5,6-二氢-4H-咪唑并[4,5,1-ij]喹啉-2-基，或 5-甲基-4,5-二氢咪唑并[1,5,4-de][1,4]苯并恶嗪-2-基、5,6,7-四氢咪唑并[4,5,1-jk][1,4]苯并二氮杂卓-2-基团，可选择在第 6 位被苯基甲基取代，以及它们与药学上可接受的酸的加成盐。本发明的化合物是 5-HT₃ 和 5-HT₄ 型血清素受体的配体。
• Pfaendler, Hans Rudolf; Weisner, Frank, Heterocycles, 1995, vol. 40, # 2, p. 717 - 728
  作者：Pfaendler, Hans Rudolf、Weisner, Frank

  DOI：——

  日期：——
• US5589476A
  申请人：——

  公开号：US5589476A

  公开（公告）日：1996-12-31
• 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
  作者：Michael J. Kukla、Henry J. Breslin、Rudi Pauwels、Cynthia L. Fedde、Milton Miranda、Malcolm K. Scott、Ronald G. Sherrill、Alfons Raeymaekers、Jozef Van Gelder

  DOI：10.1021/jm00106a040

  日期：1991.2

  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.