N-(5-nitro-2,3-dihydro-1H-inden-2-yl)-N-propylpropanamide | 162743-09-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: N-(5-nitro-2,3-dihydro-1H-inden-2-yl)-N-propylpropanamide
• CAS: 162743-09-1
• 化学式: C₁₅H₂₀N₂O₃
• 分子量: 276.335
• InChiKey: NKMOMPUDUKKVPA-UHFFFAOYSA-N

物化性质

• 沸点：
  433.1±45.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 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：
  66.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(5-nitro-2,3-dihydro-1H-inden-2-yl)-N-propylpropanamide 在 10percent Pd/C 硼烷 、 甲酸铵 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， 反应 3.75h， 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 硫酸 、 硼烷 、 硝酸 、 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 硝基甲烷 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 1.0h， 生成 N-(5-nitro-2,3-dihydro-1H-inden-2-yl)-N-propylpropanamide
  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：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
• US5639778A
  申请人：——

  公开号：US5639778A

  公开（公告）日：1997-06-17
• [EN] INDOLETETRALINS HAVING DOPAMINERGIC ACTIVITY<br/>[FR] INDOLETETRALINES A ACTIVITE DOPAMINERGIQUE
  申请人：THE UPJOHN COMPANY

  公开号：WO1994021608A1

  公开（公告）日：1994-09-29

  (EN) A compound of formula (I) and pharmaceutically acceptable salts thereof, where Z is R3 and X and Y form (a), or X is R3 and Y and Z form (a), (b) or (c); R1 and R2 are independently hydrogen, C1-6 alkyl, C3-7 cycloalkyl, -CH2-C3-7 cycloalkyl, phenyl (optionally substituted with halogen or C1-6 alkyl), -thiophenyl (optionally substituted with halogen or C1-6 alkyl), or C1-6 alkyl phenyl; R3 are independently hydrogen, halogen, -O-C1-6 alkyl or C1-6 alkyl; R4 is a valence bond, CH2 or oxygen; R5 and R6 are independently hydrogen, sulfur, -S-C1-6 alkyl, halogen, CON(R3)2, -COCF3, -CO-C1-6 alkyl, -CO phenyl, oxygen, -CHO, CN except that when Y and Z form (b), R1 and R2 are hydrogen or a C1-6 alkyl and R3 is hydrogen, then at least one of R5 and R6 must be other than hydrogen. These compounds and derivatives thereof exhibit dopamine-receptor stimulating activity in mammals which are useful for treating hyperprolactinemia, galactorrhea, amenorrhea, impotence, Parkinsonism, diabetes, acromegaly, hypertension and other central nervous system disorders which respond to dopamine-receptor stimulation.(FR) Composé de la formule (I) et sels pharmaceutiquement acceptables du composé; dans laquelle Z représente R3 et X et Y forment (a), ou X représente R3 et Y et Z forment (a), (b) ou (c); R1 et R2 représentent indépendamment hydrogène, C1-6 alkyle, C3-7 cycloalkyle, -CH2-C3-7 cycloalkyle, phényle (éventuellement substitué par halogène ou C1-6 alkyle), -thiophényle (éventuellement substitué par halogène ou C1-6 alkyle), ou C1-6 alkyle phényle; R3 représente indépendamment hydrogène, halogène, -O-C1-6 alkyle ou C1-6 alkyle; R4 représente une liaison de valence, CH2 ou oxygène; R5 et R6 représentent indépendamment hydrogène, soufre, -S-C1-6 alkyle, halogène, CON(R3)2, -COCF3, -CO-C1-6 alkyle, -CO phényle, oxygène, -CHO, CN, sauf que lorsque Y et Z forment (b), que R1 et R2 représentent hydrogène ou un C1-6 alkyle et que R3 représente hydrogène, R5 et/ou R6 ne doivent pas représenter hydrogène. Ces composés ainsi que leurs dérivés, présentent une activité de stimulation de récepteur de dopamine chez les mammifères, et conviennnent au traitement de l'hyperprolactinémie, la galactorrhée, l'aménorrhée, l'impuissance, la maladie de Parkinson, le diabète, l'acromégalie, l'hypertension et d'autres troubles du système nerveux central qui réagissent à la stimulation du récepteur de dopamine.
• 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.