5-amino-2-(N,N-di-n-propylamino)indan | 162743-13-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 5-amino-2-(N,N-di-n-propylamino)indan
• 英文别名: (R)-(-)-5-amino-2-N,N-dipropylaminoindane；N,N-Dipropyl-indan-2,5-diamine；2-N,2-N-dipropyl-2,3-dihydro-1H-indene-2,5-diamine
• CAS: 162743-13-7
• 化学式: C₁₅H₂₄N₂
• 分子量: 232.369
• InChiKey: QVYJMZBUSHMHKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  potassium thioacyanate 、 5-amino-2-(N,N-di-n-propylamino)indan 在 溴 、 溶剂黄146 作用下， 反应 1.5h， 以41%的产率得到2-amino-6-(N,N-di-n-propylamino)thiazolo[4,5-f]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 10percent Pd/C 硫酸 、 硼烷 、 硝酸 、 甲酸铵 、 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 硝基甲烷 、 二氯甲烷 、 乙酸乙酯 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

文献信息

• [EN] NEW 2-AMINOTHIAZOL-FUSED 2-AMINOINDANS AND 2-AMINOTETRALINS AND THEIR USE<br/>[FR] NOUVEAUX 2-AMINOINDANES ET 2-AMINOTETRALINES CONDENSES AU 2-AMINOTHIAZOL ET LEUR UTILISATION
  申请人：WIKSTROEM HAKAN VILHELM

  公开号：WO2000001680A1

  公开（公告）日：2000-01-13

  The invention relates to 2-aminothiazol-fused 2-aminoindans and 2-aminotetralins having general formula (1): wherein R1 and R2, which may be identical or different, are selected from the group consisting of a hydrogen atom, alkyl or haloalkyl groups of 1 to 7 carbon atoms, (alkyl)cycloalkyl groups of 3 to 7 carbon atoms, alkenyl or alkynyl groups of 3 to 6 carbon atoms, arylalkyl having 1 to 3 carbon atoms in the alkyl moiety, whilst the aryl nucleus may be substituted; and n and m are 1 or 2; and the enantiomers and the acid addition salts thereof, pharmaceutical compositions containing them and their use in the preparation of medicaments having an effect on the dopaminergic system of the central nervous system and/or the circulation.

  本发明涉及具有一般式（1）的2-氨基噻唑并2-氨基茚和2-氨基四氢萘，其中R1和R2可以相同也可以不同，选自氢原子，1至7个碳原子的烷基或卤代烷基，3至7个碳原子的（烷基）环烷基，3至6个碳原子的烯基或炔基，1至3个碳原子的芳基烷基，而芳基核可以被取代；n和m为1或2；以及其对映体和酸加成盐，含有它们的制药组合物以及它们在制备对中枢神经系统和/或循环的多巴胺能作用的药物方面的用途。
• 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##
• 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
• NEW 2-AMINOTHIAZOL-FUSED 2-AMINOINDANS AND 2-AMINOTETRALINS AND THEIR USE
  申请人：WIKSTRÖM, Hakan Vilhelm

  公开号：EP1091946A1

  公开（公告）日：2001-04-18