N-Indan-2-yl-N-propyl-propionamide | 162743-08-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: N-Indan-2-yl-N-propyl-propionamide
• 英文别名: N-(2,3-dihydro-1H-inden-2-yl)-N-propylpropanamide
• CAS: 162743-08-0
• 化学式: C₁₅H₂₁NO
• 分子量: 231.338
• InChiKey: NBXAEWKURNJVNA-UHFFFAOYSA-N

物化性质

• 沸点：
  368.1±32.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-Indan-2-yl-N-propyl-propionamide 在 10percent Pd/C 硫酸 、 硼烷 、 硝酸 、 甲酸铵 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 硝基甲烷 为溶剂， 反应 4.75h， 生成 5-amino-2-(N,N-di-n-propylamino)indan
  参考文献：
  名称：

  Thiazoloindans and Thiazolobenzopyrans:  A Novel Class of Orally Active Central Dopamine (Partial) Agonists

  摘要：

  The 2-aminothiazole moiety has proven its value in medicinal chemistry as a stable and lipophilic bioisosteric replacement of a phenol group. This approach has provided dopamine (DA) agonists with good oral availability. To further explore its use in the development of DA agonists, we have combined the 2-aminothiazole moiety with 2-aminoindans and 3-aminobenzopyrans, which are known templates for DA agonists. In this study we have synthesized 6-amino-3-(N,N-di-n-propylamino)-3,4-dihydro-2H-thiazole[5,4-f]-[1]benzopyran (12) and 6-amino-2-(N,N-di-n-propylamino)thiazolo[4,5-f]indan (20) and several analogues (13, 17, and 21). The affinity of the thiazolobenzopyrans and thiazoloindans for DA receptors was evaluated, which revealed compound 20 to have high affinity for DA DQ receptors. In addition, the compounds were screened for their potential to inhibit lipid peroxidation, to determine their radical scavenging properties. Compounds 12, 20, and 21 were subjected to further pharmacological evaluation in a functional assay to determine intrinsic activity. Compound 20 was also studied with microdialysis (to determine effects on DA turnover in striatum) and in unilaterally 6-OH-DA lesioned rats (to determine their potential as DA agonists). These studies selected compound 20 (GMC 1111) as particularly interesting. Compound 20 caused a rotation activation in unilaterally B-OH-DA lesioned rats and an increase in DA turnover in rat striatum. This dual agonist/antagonist action is best accounted for by its partial agonism at striatal DA D-2 receptors. Interestingly, 20 displayed long-lasting activity and excellent oral availability in B-OH-DA lesioned rats, making this compound potentially useful for the treatment of Parkinson's disease.

  DOI：

  10.1021/jm000087z
• 作为产物：
  描述：

  2-氨基茚满盐酸盐 在 硼烷 、 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 N-Indan-2-yl-N-propyl-propionamide
  参考文献：
  名称：

  Thiazoloindans and Thiazolobenzopyrans:  A Novel Class of Orally Active Central Dopamine (Partial) Agonists

  摘要：

  The 2-aminothiazole moiety has proven its value in medicinal chemistry as a stable and lipophilic bioisosteric replacement of a phenol group. This approach has provided dopamine (DA) agonists with good oral availability. To further explore its use in the development of DA agonists, we have combined the 2-aminothiazole moiety with 2-aminoindans and 3-aminobenzopyrans, which are known templates for DA agonists. In this study we have synthesized 6-amino-3-(N,N-di-n-propylamino)-3,4-dihydro-2H-thiazole[5,4-f]-[1]benzopyran (12) and 6-amino-2-(N,N-di-n-propylamino)thiazolo[4,5-f]indan (20) and several analogues (13, 17, and 21). The affinity of the thiazolobenzopyrans and thiazoloindans for DA receptors was evaluated, which revealed compound 20 to have high affinity for DA DQ receptors. In addition, the compounds were screened for their potential to inhibit lipid peroxidation, to determine their radical scavenging properties. Compounds 12, 20, and 21 were subjected to further pharmacological evaluation in a functional assay to determine intrinsic activity. Compound 20 was also studied with microdialysis (to determine effects on DA turnover in striatum) and in unilaterally 6-OH-DA lesioned rats (to determine their potential as DA agonists). These studies selected compound 20 (GMC 1111) as particularly interesting. Compound 20 caused a rotation activation in unilaterally B-OH-DA lesioned rats and an increase in DA turnover in rat striatum. This dual agonist/antagonist action is best accounted for by its partial agonism at striatal DA D-2 receptors. Interestingly, 20 displayed long-lasting activity and excellent oral availability in B-OH-DA lesioned rats, making this compound potentially useful for the treatment of Parkinson's disease.

  DOI：

  10.1021/jm000087z

文献信息

• Indoletetralins having dopaminergic activity
  申请人：Pharmacia & Upjohn Company

  公开号：US05639778A1

  公开（公告）日：1997-06-17

  A compound of formula (I) and pharmaceutically acceptable salts thereof, where Z is R.sub.3 and X and Y form (a), or X is R.sub.3 and Y and Z form (a) or (b); R.sub.1 and R.sub.2 are independently hydrogen, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, --CH.sub.2 --C.sub.3-7 cycloalkyl, phenyl (optionally substituted with halogen or C.sub.1-6 alkyl), -thiophenyl (optionally substituted with halogen or C.sub.1-6 alkyl), or C.sub.1-6 alkyl phenyl; R.sub.3 are independently hydrogen, halogen, --O--C.sub.1-6 alkyl or C.sub.1-6 alkyl; R.sub.4 is a valence bond, CH.sub.2 or oxygen; R.sub.5 and R.sub.6 are independently hydrogen, sulfur, --S--C.sub.1-6 alkyl, halogen, CON(R.sub.3).sub.2, --COCF.sub.3, --CO--C.sub.1-6 alkyl, --CO phenyl, oxygen, --CHO, CN except that when Y and Z form (b), R.sub.1 and R.sub.2 are hydrogen or a C.sub.1-6 alkyl and R.sub.3 is hydrogen, then at least one of R.sub.5 and R.sub.6 must be other than hydrogen. These compounds and derivatives thereof exhibit dopamine-receptor stimulating activity in mammals. ##STR1##

  式(I)的化合物及其药学上可接受的盐，其中Z为R.sub.3，而X和Y形成(a)，或者X为R.sub.3，而Y和Z形成(a)或(b)；R.sub.1和R.sub.2独立地为氢、C.sub.1-6烷基、C.sub.3-7环烷基、--CH.sub.2 --C.sub.3-7环烷基、苯基（可选地取代卤素或C.sub.1-6烷基）、-噻吩基（可选地取代卤素或C.sub.1-6烷基）或C.sub.1-6烷基苯基；R.sub.3独立地为氢、卤素、--O--C.sub.1-6烷基或C.sub.1-6烷基；R.sub.4为价键、CH.sub.2或氧；R.sub.5和R.sub.6独立地为氢、硫、--S--C.sub.1-6烷基、卤素、CON（R.sub.3）.sub.2、--COCF.sub.3、--CO--C.sub.1-6烷基、--CO苯基、氧、--CHO、CN，但当Y和Z形成(b)时，R.sub.1和R.sub.2为氢或C.sub.1-6烷基，R.sub.3为氢，则R.sub.5和R.sub.6中至少有一个不能为氢。这些化合物及其衍生物在哺乳动物中表现出多巴胺受体刺激活性。##STR1##
• 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。
• INDOLETETRALINS HAVING DOPAMINERGIC ACTIVITY
  申请人：THE UPJOHN COMPANY

  公开号：EP0690843A1

  公开（公告）日：1996-01-10
• Formyl- or cyano- substituted indole derivatives having dopaminergic activity
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP0690843B1

  公开（公告）日：2000-08-30
• 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