(R)-1-methoxy-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one | 166742-81-0

• 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: (R)-1-methoxy-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one
• 英文别名: (R)-5-Methylamino-1-methoxy-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one；(R)-5,6-Dihydro-1-methoxy-5-(methylamino)4H-imidazo[4,5,1-ij]quinolin-2-one；(10R)-3-methoxy-10-(methylamino)-1,3-diazatricyclo[6.3.1.04,12]dodeca-4,6,8(12)-trien-2-one
• CAS: 166742-81-0
• 化学式: C₁₂H₁₅N₃O₂
• 分子量: 233.27
• InChiKey: CENMUYNVSGANHE-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  44.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-1-methoxy-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one 在 聚合甲醛 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 以89%的产率得到(R)-5-Dimethylamino-1-methoxy-5,6-dihydro-4H-imidazo[ 4,5,1-ij]quinolin-2(1H)-one
  参考文献：
  名称：

  Heterocyclic amines having central nervous system activity

  摘要：

  含有抗焦虑和抗抑郁活性以及以下结构式的中枢神经系统活性的三环氮含有化合物：##STR1##及其药学上可接受的盐，其中R.sub.1和R.sub.2独立地是氢、C.sub.1-6烷基或R.sub.1和R.sub.2连接形成吡咯烷、哌啶、吗啉或咪唑。X为OCH.sub.3、SO.sub.2 R.sub.3、SO.sub.2 CF.sub.3或CN，其中R.sub.3为C.sub.1-6烷基或芳基；Y为氢、Cl、Br、F、CN、CONR.sub.1 R.sub.2、CF.sub.3、OCH.sub.3、SO.sub.2 NR.sub.1 R.sub.2。这些新化合物适用于治疗焦虑障碍、精神分裂症、帕金森病、焦虑、抑郁或作为降低血压或治疗偏头痛的化合物，适用于需要此类治疗的患者。

  公开号：

  US05652245A1
• 作为产物：
  描述：

  (R)-benzyl 1-methoxy-2-oxo-2,4,5,6-tetrahydro-1H-imidazo[4,5,1-ij]quinolin-5-yl(methyl)carbamate 在 氢气 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以70%的产率得到(R)-1-methoxy-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one
  参考文献：
  名称：

  Novel Bivalent Ligands Based on the Sumanirole Pharmacophore Reveal Dopamine D₂ Receptor (D₂R) Biased Agonism

  摘要：

  The development of bivalent ligands has attracted interest as a way to potentially improve the selectivity and/or affinity for a specific receptor subtype. The ability to bind two distinct receptor binding sites simultaneously can allow the selective activation of specific G-protein dependent or beta-arrestin-mediated cascade pathways. Herein, we developed an extended SAR study using sumanirole (1) as the primary pharmacophore. We found that substitutions in the N-1- and/or N-S-positions, physiochemical properties of those substituents, and secondary aromatic pharmacophores can enhance agonist efficacy for the cAMP inhibition mediated by G(i/o)-proteins, while reducing or suppressing potency and efficacy toward beta-arrestin recruitment. Compound 19 was identified as a new lead for its selective D-2 G-protein biased agonism with an EC50 in the subnanomolar range. Structure activity correlations were observed between substitutions in positions N-1 and/or N-5 of 1 and the capacity of the new bivalent compounds to selectively activate G-proteins versus beta-arrestin recruitment in D2R-BRET functional assays.

  DOI：

  10.1021/acs.jmedchem.6b01875

文献信息

• HETEROCYCLIC AMINES HAVING CENTRAL NERVOUS SYSTEM ACTIVITY
  申请人：——

  公开号：US20010009916A1

  公开（公告）日：2001-07-26

  Tricyclic nitrogen containing compounds, having anxiolytic and anti-depressant activity and central nervous system activity of the following structural formula: 1 and pharmaceutically acceptable salts thereof wherein R 1 and R 2 are independently hydrogen. C 1-6 alkyl or R 1 and R 2 are joined to form pyrrolidine, piperidine, morpholine or imidazole. X is OCH 3 , SO 2 R 3 , SO 2 CF 3 or CN where R 3 is C 1-6 alkyl or an Aryl; and Y is hydrogen, Cl, Br, F, CN, CONR 1 R 2 , CF 3 , OCH 3 , SO 2 NR 1 R 2 . These new compounds are suitable for treating anxiolytic disorder, schizophrenia, Parkinson's disease, anxiety, depression or as compounds for lowering blood pressure or treating migraine headaches in patients in need of such treatment.

  含有三环氮的化合物，具有抗焦虑和抗抑郁活性以及以下结构式的中枢神经系统活性：1和其药学上可接受的盐，其中R1和R2独立地为氢、C1-6烷基或R1和R2连接形成吡咯烷、哌啶、吗啉或咪唑。X为OCH3、SO2R3、SO2CF3或CN，其中R3为C1-6烷基或芳基；Y为氢、Cl、Br、F、CN、CONR1R2、CF3、OCH3、SO2NR1R2。这些新化合物适用于治疗焦虑症、精神分裂症、帕金森病、焦虑、抑郁或作为降低血压或治疗偏头痛的化合物，适用于需要此类治疗的患者。
• US5652245A
  申请人：——

  公开号：US5652245A

  公开（公告）日：1997-07-29
• US7074927B2
  申请人：——

  公开号：US7074927B2

  公开（公告）日：2006-07-11
• USRE40278E1
  申请人：——

  公开号：USRE40278E1

  公开（公告）日：2008-04-29
• USRE38452E1
  申请人：——

  公开号：USRE38452E1

  公开（公告）日：2004-03-02