2-(cyanomethyl)tetrahydroquinoline | 5100-75-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-(cyanomethyl)tetrahydroquinoline
• 英文别名: (+/-)-2-Cyanomethyl-1,2,3,4-tetrahydroquinoline；(1,2,3,4-tetrahydroquinolin-2-yl)acetonitrile；2-(1,2,3,4-tetrahydroquinolin-2-yl)acetonitrile；2-Cyanmethyl-1,2,3,4-tetrahydro-chinolin；2-Cyanomethyl-1,2,3,4-tetrahydroquinoline
• CAS: 5100-75-4
• 化学式: C₁₁H₁₂N₂
• 分子量: 172.23
• InChiKey: QZTBXCDPHAWCOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  35.8
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  2-(cyanomethyl)tetrahydroquinoline 在 盐酸 、 氯化亚砜 作用下， 生成 methyl (S)-1,2,3,4-tetrahydroquinoline-2-acetate
  参考文献：
  名称：

  2-取代的四氢喹啉的酶促拆分。三环喹喔啉二酮作为有效NMDA-甘氨酸拮抗剂的简便方法

  摘要：

  描述了使用酶促拆分导致对映体纯的三环喹喔啉二酮类NMDA-甘氨酸拮抗剂的两种方法。使用α-胰凝乳蛋白酶将中间体1,2,3,4-四氢喹啉-2-羧酸外消旋甲基1,2,3,4-四氢喹啉-2-羧酸酯3拆分为（S）-3，收率为97％ee，收率为47％（E = 67）。在一个改进的方法中，另一种中间体，外消旋甲基-1,2,3,4-四氢喹啉-2-乙酸乙酯水解4，用的Novozym ® 435提供所需的（小号） - 4在高对映选择性和产率（93％ee的，50 ％，E = 94）。

  DOI：

  10.1016/s0957-4166(98)00484-4
• 作为产物：
  描述：

  1,2,3,4-四氢喹啉-2-羧酸 在 咪唑 、 lithium aluminium tetrahydride 、 氯化亚砜 、 碘 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 生成 2-(cyanomethyl)tetrahydroquinoline
  参考文献：
  名称：

  2-取代的四氢喹啉的酶促拆分。三环喹喔啉二酮作为有效NMDA-甘氨酸拮抗剂的简便方法

  摘要：

  描述了使用酶促拆分导致对映体纯的三环喹喔啉二酮类NMDA-甘氨酸拮抗剂的两种方法。使用α-胰凝乳蛋白酶将中间体1,2,3,4-四氢喹啉-2-羧酸外消旋甲基1,2,3,4-四氢喹啉-2-羧酸酯3拆分为（S）-3，收率为97％ee，收率为47％（E = 67）。在一个改进的方法中，另一种中间体，外消旋甲基-1,2,3,4-四氢喹啉-2-乙酸乙酯水解4，用的Novozym ® 435提供所需的（小号） - 4在高对映选择性和产率（93％ee的，50 ％，E = 94）。

  DOI：

  10.1016/s0957-4166(98)00484-4

文献信息

• Tricyclic quinoxalinediones
  申请人：Sumitomo Pharmaceuticals Company, Limited

  公开号：US05616586A1

  公开（公告）日：1997-04-01

  Tricyclic quinoxalinediones of the formula: ##STR1## wherein X is alkyl, halogen, cyano, trifluoromethyl, nitro, hydroxy, amino, etc.; R.sup.1 is H, etc.; R.sup.2 is H, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, arylalkyl, substituted arylalkyl, aryl, or substituted aryl; W is H, CO.sub.2 R.sup.3, CO.sub.2 Y, CONR.sup.3 R.sup.4, CONR.sup.3 Y, CON(OR.sup.3)R.sup.4, COR.sup.3, CN, tetrazolyl, or substituted alkyl; R.sup.3 and R.sup.4 independently are H, alkyl, cycloalkyl, alkenyl, alkynyl, etc.; Y is mono-substituted alkyl or di-substituted alkyl; and n is an integer 0 or 1, or a pharmaceutically acceptable salt thereof, which are useful as a selective antagonist of glutamate receptor for the treatment or prevention of various diseases in animals including human being, for example, minimizing damage of central nervous system induced by ischaemic or hypoxylic conditions, treatment and/or prevention of neurodegenerative disorders, and further analgesics, antidepressants, anxiolitics, and anti-schizophrenics.

  Tricyclic quinoxalinediones的中文翻译：其中X是烷基、卤素、氰基、三氟甲基、硝基、羟基、氨基等；R.sup.1是H等；R.sup.2是H、烷基、环烷基、烯基、炔基、环烷基烷基、芳基烷基、取代芳基烷基、芳基或取代芳基；W是H、CO.sub.2 R.sup.3、CO.sub.2 Y、CONR.sup.3 R.sup.4、CONR.sup.3 Y、CON(OR.sup.3)R.sup.4、COR.sup.3、CN、四唑基或取代烷基；R.sup.3和R.sup.4独立地是H、烷基、环烷基、烯基、炔基等；Y是单取代烷基或双取代烷基；n是整数0或1，或其药学上可接受的盐，可用作选择性谷氨酸受体拮抗剂，用于治疗或预防动物包括人类的各种疾病，例如，减少由缺血或低氧条件引起的中枢神经系统损伤，治疗和/或预防神经退行性疾病，以及进一步的镇痛剂、抗抑郁药、抗焦虑药和抗精神分裂症药物。
• Tricyclic quinoxalinedione derivatives
  申请人：Sumitomo Pharmaceuticals Co., Ltd.

  公开号：US05719152A1

  公开（公告）日：1998-02-17

  A tricyclic quinoxalinedione derivative represented by the formula 1: ##STR1## wherein X represents hydrogen, alkyl, halogen, cyano, trifluoromethyl, or nitro; R.sup.1 represents hydrogen, alkyl, cycloalkyl, or cycloalkylalkyl; G represents --CONR.sup.2 -- or --NR.sup.2 CO--, wherein R.sup.2 represents hydrogen or alkyl; J represents an acidic group or a group which is convertible thereto in vivo; E represents an basic group or a group which is convertible thereto in vivo; Y represents a single bond, alkylene, alkenylene, substituted alkylene, or Y.sup.1 --Q--Y.sup.2, wherein Y.sup.1 represents a single bond or alkylene, Y.sup.2 represents alkylene, and Q represents a heteroatom selected from oxygen or sulfur; Z represents alkylene, or a pharmaceutically acceptable salt thereof, these compounds are selective antagonists of glycine binding site of the NMDA receptor.

  一种三环喹喔啉二酮衍生物，其化学式为1：##STR1## 其中X代表氢、烷基、卤素、氰基、三氟甲基或硝基；R.sup.1代表氢、烷基、环烷基或环烷基烷基；G代表--CONR.sup.2--或--NR.sup.2CO--，其中R.sup.2代表氢或烷基；J代表酸性基团或可在体内转化为酸性基团的基团；E代表碱性基团或可在体内转化为碱性基团的基团；Y代表单键、烷基、烯基、取代烷基或Y.sup.1--Q--Y.sup.2，其中Y.sup.1代表单键或烷基，Y.sup.2代表烷基，Q代表从氧或硫选择的杂原子；Z代表烷基，或其药学上可接受的盐，这些化合物是NMDA受体的选择性甘氨酸结合位点拮抗剂。
• Synthesis of tetrahydroquinoline derivatives via electrochemical hydrocyanomethylation or hydrogenation of quinolines with MeCN
  作者：Jie Xia、Dahan Wang、Ruitong Yang、Yujie Deng、Guo-Jun Deng

  DOI：10.1039/d4gc00164h

  日期：——

  A series of tetrahydroquinoline derivatives were selectively synthesized at room temperature via electrochemical hydrocyanomethylation of quinoline skeletons using acetonitrile as both a hydrogen source and a cyanomethyl precursor. When a bulky substituent was present at the C2 position, hydrogenation of quinoline derivatives dominated. Furthermore, a deuterium labeling experiment revealed that protons

  以乙腈为氢源和氰甲基前驱体，通过喹啉骨架的电化学氢氰甲基化，在室温下选择性合成了一系列四氢喹啉衍生物。当C2位置存在大取代基时，喹啉衍生物的氢化反应占主导地位。此外，氘标记实验表明质子源自乙腈。该方法具有条件温和、效率高、底物范围广、官能团耐受性好等特点。
• Tricyclic Quinoxalinediones: 5,6-Dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-Dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones as Potent Antagonists for the Glycine Binding Site of the NMDA Receptor
  作者：Ryu Nagata、Norihiko Tanno、Toru Kodo、Nobuyuki Ae、Hiroshi Yamaguchi、Tamiki Nishimura、Fujio Antoku、Tohru Tatsuno、Terufumi Kato

  DOI：10.1021/jm00049a015

  日期：1994.11

  A series of tricyclic quinoxalinediones, 5,6-dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones, were synthesized and was evaluated for their affinity for the glycine binding site of the NMDA receptor using a [H-3]- 5,7-dichlorokynurenic acid binding assay. The six-membered ring-fused tricyclic quinoxalinedione 18g (K-i = 9.9 nM) displayed high affinity for the glycine site. The anilide derivative 20g (K-i = 2.6 nM) was 4-fold more potent than 18g and as potent as L-689,560, one of the most potent glycine antagonists so far prepared. Although the carboxylic acid derivative of the corresponding five-membered ring-fused tricyclic quinoxalinedione 18e (K-i = 7.3 nM) had affinity comparable to that of 18g, the anilide derivative 20e largely decreased in the affinity in contrast to 20g. Enantiomers 23g, 24g, 25g, and 26g were prepared and tested. Only the S enantiomer 25g (K-i = 0.96 nM) retained the affinity among the anilide derivatives, whereas both enantiomers 23g (K-i = 2.3 nM) and 24g (K-i = 9.6 nM) were active among the carboxylic acid derivatives. The origin of the high affinity of carboxylic acid derivatives such as 18e and 18g would be a charge-charge interaction between the anionic carboxylate residues of the compounds and the cationic proton-donor site in the receptor.
• Windeck, Anne-Kathrin; Hess, Ulrich; Steckhan, Eberhard, Liebigs Annalen, 1996, # 9, p. 1471 - 1476
  作者：Windeck, Anne-Kathrin、Hess, Ulrich、Steckhan, Eberhard、Reck, Guenter

  DOI：——

  日期：——