N-(tert-butyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxamide | 960314-41-4

• 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
• 英文名称: N-(tert-butyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxamide
• 英文别名: N-tert-butyl-1,2,3,4-tetrahydroisoquinoline-1-carboxamide
• CAS: 960314-41-4
• 化学式: C₁₄H₂₀N₂O
• 分子量: 232.326
• InChiKey: YJJQLTHWIOZULQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(tert-butyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxamide 、 9,10-difluoro-2,3-dihydro-3-(S)-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid 以 二甲基亚砜 为溶剂， 以82%的产率得到
  参考文献：
  名称：

  Novel ofloxacin derivatives: Synthesis, antimycobacterial and toxicological evaluation

  摘要：

  Thirty novel 9-fluoro-2,3-dihydro-8,10-(mono/di-sub)-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acids were synthesized from 2,3,4,5-tetrafluoro benzoic acid and evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC2) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from mycobacteria. Among the synthesized compounds, 10-[2-carboxy-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]-9-fluoro-2,3-dihydro-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid was found to be the most active compound in vitro with MIC99 of 0.19 mu M and 0.09 mu M against MTB and MTR-TB, respectively. In the in vivo animal model also the same compound decreased the bacterial load in lung and spleen tissues with 1.91 and 2.91 - log 10 protections, respectively, at the dose of 50 mg/ kg body weight. Compound 10-[(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)]-9-fluoro-2,3-dihydro-3-methyl-8-nitro-7-oxo7H-[1,4]oxazino[2,3,4-]quinoline-6-carboxylic acid was found to be the most active in the inhibition of the supercoiling activity of DNA gyrase with an IC50 of 10.0 mu g/mL. The results demonstrate the potential and importance of developing new oxazino quinolone derivatives against mycobacterial infections. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.110
• 作为产物：
  描述：

  四氢异喹啉 在 catalase from Micrococcus lysodeikticus 、 水 、 氧气 、 monoamine oxidase P₁-H₁₂ 作用下， 以 aq. buffer 为溶剂， 反应 45.0h， 生成 N-(tert-butyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxamide
  参考文献：
  名称：

  通过单胺氧化酶-Ugi-Joullié 反应序列对 1,2,3,4-四氢异喹啉进行化学酶促一锅两步功能化

  摘要：

  据报道，一种化学酶促方法可用于合成多种功能化的 1,2,3,4-四氢异喹啉。该协议将单胺氧化酶催化的亚胺形成与 Ugi-Joullié 多组分反应结合在一锅中，无需中间处理。分离了 41 种产品，并证明了克级合成。

  DOI：

  10.1002/ejoc.202101545

文献信息

• Antimycobacterial Activities of Novel 1-(Cyclopropyl/<i>tert</i>-butyl/4-fluorophenyl)-1,4-dihydro- 6-nitro-4-oxo-7-(substituted secondary amino)-1,8-naphthyridine-3-carboxylic Acid
  作者：Dharmarajan Sriram、Palaniappan Senthilkumar、Murugesan Dinakaran、Perumal Yogeeswari、Arnab China、Valakunja Nagaraja

  DOI：10.1021/jm700999n

  日期：2007.11.1

  4-dihydro-6-nitro-4-oxo-7-(substitute d secondary amino)-1,8-naphthyridine-3-carboxylic acids were synthesized and evaluated for antimycobacterial in vitro and in vivo against Mycobacterium tuberculosis H37Rv (MTB), multi-drug-resistant Mycobacterium tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC2) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis

  51个1-（环丙基/叔丁基/ 4-氟苯基）-1,4-二氢-6-硝基-4-氧代-7-（取代仲氨基）-1,8-萘啶-3-羧酸合成并评估了对结核分枝杆菌H37Rv（MTB），耐多药结核分枝杆菌（MDR-TB）和耻垢分枝杆菌（MC2）的体外和体内抗分枝杆菌的作用，还测试了其抑制DNA超螺旋活性的能力耻垢分枝杆菌的促旋酶。在合成的化合物中，1-叔丁基-1,4-二氢-7-（4,4-二甲基恶唑烷-3-基）-6-硝基-4-氧代-1,8-萘吡啶-3-羧酸（10q）被发现是体外活性最高的化合物，对MTB和MDR-TB的MIC为0.1 microM，分别比异烟肼对MTB和MDR-TB的效力分别高3倍和455倍。
• Synthesis and<i>in-vitro</i>Antimycobacterial Evaluation of 1-(Cyclopropyl/2,4-difluorophenyl/<i>tert-</i>butyl)-1,4-dihydro- 8-methyl-6-nitro-4-oxo-7-(substituted secondary amino)quinoline-3-carboxylic acids
  作者：Palaniappan Senthilkumar、Murugesan Dinakaran、Yogesh Chandraseakaran、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1002/ardp.200800015

  日期：2009.2

  Fifty one newer 1‐(cyclopropyl/2,4‐difluorophenyl/tert‐butyl)‐1,4‐dihydro‐8‐methyl‐6‐nitro‐4‐oxo‐7‐(substituted secondary amino)quinoline‐3‐carboxylic acids were synthesized from 1,3‐dichloro‐2‐methylbenzene and evaluated for in‐vitro antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi‐drug resistant Mycobacterium tuberculosis (MDR‐TB), and Mycobacterium smegmatis (MC2)

  五十一种新型 1-(环丙基/2,4-二氟苯基/叔丁基)-1,4-二氢-8-甲基-6-硝基-4-氧代-7-(取代仲氨基)喹啉-3-羧酸由 1,3-二氯-2-甲苯合成，并评估了体外抗结核分枝杆菌 H37Rv (MTB)、耐多药结核分枝杆菌 (MDR-TB) 和耻垢分枝杆菌 (MC2) 的活性。在合成的化合物中，1-环丙基-1,4-二氢-7-(3,4-二氢-6,7-二甲氧基异喹啉-2(1H)-基)-8-甲基-6-硝基-4-氧喹啉-发现 3-羧酸 9p 是体外活性最强的化合物，对 MTB 的 MIC 值为 0.39 μM。抗耐多药结核病，化合物 7-(2-carboxy-5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-yl)-1-cyclopropyl-1，
• Process for producing optically active amides
  申请人：Ajinomoto Co., Ltd.

  公开号：EP0751128A1

  公开（公告）日：1997-01-02

  The present invention provides an industrial process for producing decahydro (4aS,8aS)isoquinoline-3(S)-carboxamides(4; R=H or C1-6 alkyl) which are useful as intermediates of Saquinavir (EP432694) that has been proposed as an anti-AIDS agent. Tetrahydroisoquinoline-3(S)-carboxylic acid (1) is reacted with at least one of phosgene, phosgene dimer and triphosgene to form N-carboxy anhydride (NCA) (2). This is reacted with an amine to produce a tetrahydroisoquinoline-3(S)-carboxamide derivative (3), which can be reduced in the presence of a metal catalyst (preferably Ru) to produce (4).

  本发明提供了一种生产十氢(4aS,8aS)异喹啉-3(S)-羧酰胺(4；R=H或C1-6烷基)的工业工艺，该羧酰胺可用作萨喹那韦(Saquinavir)(EP432694)的中间体，萨喹那韦已被提议用作抗艾滋病药物。 四氢异喹啉-3(S)-羧酸（1）与光气、光气二聚体和三光气中的至少一种反应生成 N-羧基酸酐（NCA）（2）。再与胺反应生成四氢异喹啉-3(S)-甲酰胺衍生物 (3)，在金属催化剂（最好是 Ru）作用下还原生成 (4)。
• Chlorosilane-Promoted Addition Reaction of Isocyanides to 3,4-Dihydroisoquinoline <i>N</i>-Oxides
  作者：Takahiro Soeta、Shuhei Fujinami、Yutaka Ukaji

  DOI：10.1021/jo301791m

  日期：2012.11.2

  The addition reaction Of isocyanides to 3,4-dihydroisoquindline N-oxides in the presence of TMSCl has been demonstrated, with the corresponding 1,2,3,4-tetrahydroisoquinoline-1-carboxylamides being obtained in moderate to high yields. A wide range of 3,4-dihydroisoquinoline N-oxides and isocyanides were applicable to this reaction.
• Antimycobacterial activities of novel 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid
  作者：Murugesan Dinakaran、Palaniappan Senthilkumar、Perumal Yogeeswari、Arnab China、Valakunja Nagaraja、Dharmarajan Sriram

  DOI：10.1016/j.bmc.2007.11.016

  日期：2008.3.15

  Various 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid derivatives were synthesized from 2-aminothiophenol by a five-step reaction, evaluated for in-vitro and in-vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC2), and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the thirty-four synthesized compounds, 2-(3-(diethylcarbamoyl)piperidin-1-yl)-)-3-fluoro-5,12-dihydro-5-oxobenzothiazoio[3,2a]quinoline-6-carboxylic acid (71) was found to be the most active compound in vitro with MIC of 0.18 and 0.08 mu M against MTB and MTR-TB, respectively. Compound 71 was found to be 2 and 570 times more potent than isoniazid against MTB and MDR-TB, respectively. In the in-vivo animal model 71 decreased the bacterial load in lung and spleen tissues with 2.78 and 3.12 - log 10 protections, respectively, at the dose of 50 mg/kg body weight. (C) 2007 Elsevier Ltd. All rights reserved.