5,6-dimethoxy-2-(pyrrolidino)indan

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 5,6-dimethoxy-2-(pyrrolidino)indan
• 英文别名: 5,6-Dimethoxy-2(pyrrolidino)indan；1-(5,6-dimethoxy-2,3-dihydro-1H-inden-2-yl)pyrrolidine
• 化学式: C₁₅H₂₁NO₂
• 分子量: 247.337
• InChiKey: QBLCMEXZWCBQBF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-(3,4-dimethoxy-phenyl)-propionyl chloride 在 palladium on activated charcoal 盐酸 、 三氯化铝 、 亚硝酸丁酯 、 硫酸 、 氢气 、 sodium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 溶剂黄146 、 二甲基亚砜 、 乙腈 为溶剂， 20.0~100.0 ℃ 、344.74 kPa 条件下， 反应 10.5h， 生成 5,6-dimethoxy-2-(pyrrolidino)indan
  参考文献：
  名称：

  Dopamine D₃ Receptor Antagonists. 1. Synthesis and Structure−Activity Relationships of 5,6-Dimethoxy-N-alkyl- and N-Alkylaryl-Substituted 2-Aminoindans

  摘要：

  5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D-3 receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure-activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D-3 antagonists. Thus, combinations of various alkyl groups were generally inactive at the D-3 receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D-3 binding affinity, the D-2 affinity is also enhanced, resulting in a less than 4-fold preference for the D-3 receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D-3 antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH3. Me2S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et3SiH to give the desired product 3 in good overall yield of (similar to 65%) from the indanone 5c.

  DOI：

  10.1021/jm010145w

文献信息

• 2-aminoindans as selective dopamine D3 ligands
  申请人：Pharmacia & Upjohn Company

  公开号：US05708018A1

  公开（公告）日：1998-01-13

  Compounds and their pharmaceutically acceptable salts suitable for treating central nervous system disorders associated with the dopamine D3 receptor activity of Formula I: ##STR1## wherein R.sub.1 and R.sub.2 are independently chosen from hydrogen, C.sub.1 -C.sub.8 alkyl, OCH.sub.3, OH, OSO.sub.2 CF.sub.3, OSO.sub.2 CH.sub.3, SOR.sub.5, CO.sub.2 R.sub.5, CONH.sub.2, CONR.sub.5 R.sub.6, COR.sub.5, CN, SO.sub.2 NH.sub.2, SO.sub.2 NR.sub.5 R.sub.6, SO.sub.2 R.sub.5, --OCO--(C.sub.1 -C.sub.6 alkyl), --NCO--(C.sub.1 -C.sub.6 alkyl), --CH.sub.2 O--(C.sub.1 -C.sub.6 alkyl), --CH.sub.2 OH, --CO-Aryl, --NHSO.sub.2 -Aryl, --NHSO.sub.2 --(C.sub.1 -C.sub.6 alkyl), phthalimide, thiophenyl, pyrrol, pyrrolinyl, oxazolyl, or R.sub.1 and R.sub.2 together form --O(CH.sub.2).sub.1-2 O-- or --(CH.sub.2).sub.3-6 -- (except that only one of R.sub.1 and R.sub.2 can be hydrogen or OH in any such compound); R.sub.3 and R.sub.4 are independently chosen from C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.8 alkynyl, C.sub.3 -C.sub.8 cycloalkyl, --(CH.sub.2).sub.p -- thienyl (where p is 1-4), or C.sub.1 -C.sub.8 alkyl (except where R.sub.1 or R.sub.2 are hydrogen or OH or where both R.sub.1 and R.sub.2 are OCH.sub.3 or a C.sub.1 -C.sub.8 alkyl); R.sub.5 is hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.8 cycloalkyl; and R.sub.6 is C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.8 alkynyl, C.sub.3 -C.sub.8 cycloalkyl, or Aryl.

  本发明涉及与多巴胺D3受体活性相关的中枢神经系统疾病治疗的化合物及其药学上可接受的盐，其化学式为I：##STR1##其中R.sub.1和R.sub.2分别选择自氢、C.sub.1-C.sub.8烷基、OCH.sub.3、OH、OSO.sub.2CF.sub.3、OSO.sub.2CH.sub.3、SOR.sub.5、CO.sub.2R.sub.5、CONH.sub.2、CONR.sub.5R.sub.6、COR.sub.5、CN、SO.sub.2NH.sub.2、SO.sub.2NR.sub.5R.sub.6、SO.sub.2R.sub.5、--OCO--（C.sub.1-C.sub.6烷基）、--NCO--（C.sub.1-C.sub.6烷基）、--CH.sub.2O--（C.sub.1-C.sub.6烷基）、--CH.sub.2OH、--CO-Aryl、--NHSO.sub.2-Aryl、--NHSO.sub.2--（C.sub.1-C.sub.6烷基）、邻苯二酰亚胺、噻吩基、吡咯、吡咯烷基、噁唑基，或R.sub.1和R.sub.2一起形成--O（CH.sub.2）.sub.1-2O--或--（CH.sub.2）.sub.3-6--（但是在任何这样的化合物中，R.sub.1和R.sub.2只能有一个是氢或OH）; R.sub.3和R.sub.4分别选择自C.sub.2-C.sub.4烯基、C.sub.3-C.sub.8炔基、C.sub.3-C.sub.8环烷基、--（CH.sub.2）.sub.p--噻吩基（其中p为1-4）或C.sub.1-C.sub.8烷基（除非R.sub.1或R.sub.2是氢或OH或R.sub.1和R.sub.2都是OCH.sub.3或C.sub.1-C.sub.8烷基）; R.sub.5为氢、C.sub.1-C.sub.8烷基、C.sub.2-C.sub.4烯基、C.sub.3-C.sub.8环烷基; R.sub.6为C.sub.1-C.sub.8烷基、C.sub.2-C.sub.4烯基、C.sub.2-C.sub.8炔基、C.sub.3-C.sub.8环烷基或芳基。
• Binge behavior regulators
  申请人：Golan Ezekiel

  公开号：US10137096B2

  公开（公告）日：2018-11-27

  Methods and compositions utilizing 2-aminoindan derivatives collectively represented by Formula I as described and defined in the specification for regulating binge behavior, particularly binge drinking, are disclosed.

  本发明公开了利用说明书中描述和定义的式 I 所代表的 2-氨基茚满衍生物来调节酗酒行为，特别是酗酒的方法和组合物。
• Alcoholic beverage substitutes
  申请人：Clearmind Medicine Inc.

  公开号：US11528924B2

  公开（公告）日：2022-12-20

  Alcoholic beverage-substitutes such as a beer-substitute, a wine-substitute, a cider-substitute, an alcopop-substitute or a spirit-substitute beverage, comprising a base liquid (e.g., a base beverage) and a 2-aminoindan derivative such as defined by Formula I in the specification are disclosed.

  本发明公开了酒精饮料代用品，如啤酒代用品、葡萄酒代用品、苹果酒代用品、酒精饮料代用品或烈性酒代用品，包括基础液体（如基础饮料）和2-氨基茚满衍生物（如说明书中式I所定义）。
• 2-AMINOINDANS AS SELECTIVE DOPAMINE D3 LIGANDS
  申请人：THE UPJOHN COMPANY

  公开号：EP0712387A1

  公开（公告）日：1996-05-22
• BINGE BEHAVIOR REGULATORS
  申请人：Golan, Ezekiel

  公开号：EP3230255B1

  公开（公告）日：2020-03-18