5-amino-2-N-n-propylaminoindan | 254885-64-8

• 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-propylaminoindan
• 英文别名: N2-propyl-2,3-dihydro-1H-indene-2,5-diamine；2-N-propyl-2,3-dihydro-1H-indene-2,5-diamine
• CAS: 254885-64-8
• 化学式: C₁₂H₁₈N₂
• 分子量: 190.288
• InChiKey: AYDKYQQSHWQNSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  potassium thioacyanate 、 5-amino-2-N-n-propylaminoindan 在 溴 、 溶剂黄146 作用下， 反应 1.5h， 以46%的产率得到N*6*-Propyl-6,7-dihydro-5H-1-thia-3-aza-s-indacene-2,6-diamine
  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 、 ammonium formate 、 碳酸氢钠 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 硝基甲烷 、 乙酸乙酯 为溶剂， 反应 2.75h， 生成 5-amino-2-N-n-propylaminoindan
  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

• 2-aminothiazol-fused 2-aminoindans and 2-aminotetralins and their use
  申请人：——

  公开号：US06291494B1

  公开（公告）日：2001-09-18

  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, while 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.

  该发明涉及具有通式（1）的2-氨基噻唑融合的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，选自包括氢原子、1到7个碳原子的烷基或卤代烷基基团、3到7个碳原子的（烷基）环烷基基团、3到6个碳原子的烯基或炔基基团、烷基中含有1到3个碳原子的芳基烷基，而芳基核可能被取代；n和m为1或2；以及其对映异构体和酸盐，含有它们的制剂和它们在制备对中枢神经系统和/或循环的多巴胺系统产生影响的药物中的用途。
• [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。
• 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
• US6291494B1
  申请人：——

  公开号：US6291494B1

  公开（公告）日：2001-09-18
• Thiazoloindans and Thiazolobenzopyrans:  A Novel Class of Orally Active Central Dopamine (Partial) Agonists
  作者：L. Alexander van Vliet、Nienke Rodenhuis、Håkan Wikström、Thomas A. Pugsley、Kevin A. Serpa、Leonard T. Meltzer、Thomas G. Heffner、Lawrence D. Wise、Mary E. Lajiness、Rita M. Huff、Kjell Svensson、Guido R. M. M. Haenen、Aalt Bast

  DOI：10.1021/jm000087z

  日期：2000.9.1

  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.