Sumanirole hydrochloride

• 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: Sumanirole hydrochloride
• 英文别名: (5R)-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-one hydrochloride；(R)-sumanirole hydrochloride；(-)-(R)-sumanirole hydrochloride；PNU-95666E hydrochloride salt；(5R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-one hydrochloride；(10R)-10-(methylamino)-1,3-diazatricyclo[6.3.1.04,12]dodeca-4,6,8(12)-trien-2-one;hydrochloride
• 化学式: C₁₁H₁₃N₃O*ClH
• 分子量: 239.705
• InChiKey: QWVGPCCMDHYWPX-DDWIOCJRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  44.4
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Sumanirole hydrochloride 在 sodium hydroxide 、 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 (+/-)-5,6-dihydro-5-(dimethylamino)-4H-imidazo<4,5,1-ij>quinolin-2(1H)-one
  参考文献：
  名称：

  Synthesis and Biological Activities of (R)-5,6-Dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine and Its Metabolites

  摘要：

  The imidazoquinoline (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[(R)-3] is a potent dopamine agonist when tested in animals but surprisingly shows very low affinity in in vitro binding assays. When incubated with mouse or monkey liver S9 microsomes, (R)-3 is metabolized by N-demethylation and oxidation to (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij]quinolin-2(lu)-one [(R)-6]; intermediate metabolites, where N-demethylation to the imidazoquinoline (R)-4 and where oxidation to the imidazoquinolinone (R)-5 has taken place, are also observed in these incubates. A cross-species study on the metabolism of (R)-3 in vitro has shown large variations in the extent of metabolism from species to species. Imidazoquinolinones (R)-5 and (R)-6 have comparable activity to (R)-3 in animals and also show good dopaminergic (D2) and serotonergic (5HT(1A)) activities in binding assays. It is probable that these metabolites account at least in part for the in vivo activity found for (R)-3. Efficient syntheses for compounds 3-6 as single enantiomers from quinoline are presented together with information on the biological activities and metabolic stabilities of these compounds.

  DOI：

  10.1021/jm960360q
• 作为产物：
  描述：

  (R)-5-(甲基氨基)-5,6-二氢-1H-咪唑并[4,5,1-ij]喹啉-2(4h)-酮 在 盐酸 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 2.0h， 以97%的产率得到Sumanirole hydrochloride
  参考文献：
  名称：

  α，β-不饱和醛的有机催化不对称叠氮基对映体（R）-舒马尼罗的对映选择性合成

  摘要：

  本文我们报告（的对映选择性合成- [R）-Sumanirole其中2-硝基肉桂的有机催化不对称氮杂环丙烷是关键步骤。

  DOI：

  10.1016/j.tetasy.2014.06.018

文献信息

• Remote Control of the C-3-C-4 Double-Bond Epoxidation of a Chiral 1,2-Dihydroquinoline: Application to the Synthesis of (-)-(R)-Sumanirole (PNU-95666E)
  作者：Ludivine Jean-Gérard、Frédéric Macé、Anh Ngoc Ngo、Mickaël Pauvert、Hélène Dentel、Michel Evain、Sylvain Collet、André Guingant

  DOI：10.1002/ejoc.201200344

  日期：2012.8

  synthetic approach, using a chiral Reissert adduct, was too problematic to be pursued further. In the second successful approach, the authors took advantage of the stereoselective epoxidation of a 1,2-dihydroquinoline bearing an Evans' chiral auxiliary at N-1.

  描述了从喹啉开始的 (-)-(R)-舒马尼罗的十二步合成。第一种合成方法，使用手性 Reissert 加合物，问题太大，无法进一步研究。在第二种成功的方法中，作者利用了在 N-1 处带有 Evans 手性助剂的 1,2-二氢喹啉的立体选择性环氧化。
• An asymmetric synthesis of (R)-5-(methylamino)-5,6-dihydro-4H-imidazo-[4,5,1-ij]quinolin-2(1H)-one (1) and its [2-14C]- and [6,7-3H2]-labeled forms
  作者：Richard F. Heier、Malcolm W. Moon、Wayne T. Stolle、John A. Easter、Richard S. P. Hsi

  DOI：10.1002/(sici)1099-1344(199612)38:12<1087::aid-jlcr933>3.0.co;2-o

  日期：1996.12

  1-ij]quinolin-2(1H)-one (1) is a dopamine agonist which shows selectivity for the D2 receptor subtype, and is of interest as a potential drug for the treatment of Parkinson's disease. An asymmetric epoxidation approach has been used to prepare 1 in eleven steps (15% overall yield) from 8-nitroquinoline. An advanced intermediate in this synthesis, tert-butyl (R)-methyl(8-amino-1,2,3,4-tetrahydro-3-quinolinyl)carbamate

  (R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (1) 是一种多巴胺激动剂，对 D2 受体具有选择性亚型，并作为治疗帕金森病的潜在药物而受到关注。一种不对称环氧化方法已被用于从 8-硝基喹啉制备 11 步（15% 总产率）。该合成中的高级中间体，叔丁基 (R)-甲基(8-氨基-1,2,3,4-四氢-3-喹啉基)氨基甲酸酯 (10)，已与 [ 14 C] 光气反应以提供在 C-2 位置 (236 μCi/mg) 用碳 14 标记的 1 的两步合成。1的溴化得到二溴类似物12b，其在氚气存在下被还原得到在C-6和C-7位置用氚标记的1(28.5Ci/mmol)。
• (5R)-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione and method of preparation thereof
  申请人：McCall B. Robert

  公开号：US20060040929A1

  公开（公告）日：2006-02-23

  The present invention is a method of treating sexual disturbances in humans and inducing mating in non-human mammals using the compounds of formula (A) in a dosage range where the sexually therapeutic amount is from about 0.2 thru 8 mg/person/dose and where the sexually mating amount is from about 0.003 thru 0.2 mg/kg/dose. The present invention also provides a novel pharmaceutical agent, (5R)-5 -(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione and pharmaceutically acceptable salts thereof.

  本发明涉及使用公式（A）化合物治疗人类的性障碍和诱导非人哺乳动物交配的方法，其中性治疗剂量范围为每人/次约0.2到8毫克，性交配剂量范围为每千克体重/次约0.003到0.2毫克。本发明还提供了一种新型药物，即（5R）-5-（甲基氨基）-5,6-二氢-4H-咪唑并[4,5,1-ij]喹啉-2（1H）-硫醇及其药学上可接受的盐。
• [EN] (5R)-(METHYLAMINO)-5,6-DIHYDRO-4H-IMIDAZO[4,5,1-ij]QUINOLINE-2(1H)-THIONE<br/>[FR] (5R)-(METHYLAMINO)-5,6-DIHYDRO-4H-IMIDAZO[4,5,1-ij]QUINOLINE-2(1H)-THIONE
  申请人：UPJOHN CO

  公开号：WO2001083483A1

  公开（公告）日：2001-11-08

  The present invention is a novel pharmaceutical agent, (5R)-5-(methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-2(1H)-thione (Formula I) and pharmaceutically acceptable salts thereof.
• Synthesis and Biological Activities of (<i>R</i>)-5,6-Dihydro-<i>N</i>,<i>N</i>-dimethyl-4<i>H</i>-imidazo[4,5,1-<i>ij</i>]quinolin-5-amine and Its Metabolites
  作者：Richard F. Heier、Lester A. Dolak、J. Neil Duncan、Deborah K. Hyslop、Michael F. Lipton、Iain J. Martin、Michael A. Mauragis、Montford F. Piercey、Nanette F. Nichols、Peggy J. K. D. Schreur、Martin W. Smith、Malcolm W. Moon

  DOI：10.1021/jm960360q

  日期：1997.2.1

  The imidazoquinoline (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[(R)-3] is a potent dopamine agonist when tested in animals but surprisingly shows very low affinity in in vitro binding assays. When incubated with mouse or monkey liver S9 microsomes, (R)-3 is metabolized by N-demethylation and oxidation to (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij]quinolin-2(lu)-one [(R)-6]; intermediate metabolites, where N-demethylation to the imidazoquinoline (R)-4 and where oxidation to the imidazoquinolinone (R)-5 has taken place, are also observed in these incubates. A cross-species study on the metabolism of (R)-3 in vitro has shown large variations in the extent of metabolism from species to species. Imidazoquinolinones (R)-5 and (R)-6 have comparable activity to (R)-3 in animals and also show good dopaminergic (D2) and serotonergic (5HT(1A)) activities in binding assays. It is probable that these metabolites account at least in part for the in vivo activity found for (R)-3. Efficient syntheses for compounds 3-6 as single enantiomers from quinoline are presented together with information on the biological activities and metabolic stabilities of these compounds.