6-{4-[(3,4-dihydro-2H-chromen-2-ylmethyl)amino]butyl}-1H-imidazo[1,5-c][1,3]thiazole-5,7(6H,7aH)-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 6-{4-[(3,4-dihydro-2H-chromen-2-ylmethyl)amino]butyl}-1H-imidazo[1,5-c][1,3]thiazole-5,7(6H,7aH)-dione
• 英文别名: (+/-)-2-[4-[(chroman-2-yl)methylamine]butyl]-1,3-dioxoperhydroimidazo[1,5-c]-thiazol；(+/-)-2-[4-[(chroman-2-yl)methylamino]butyl]-1,3-dioxoperhydroimidazo[1,5-c]thiazole；6-[4-(3,4-dihydro-2H-chromen-2-ylmethylamino)butyl]-3,7a-dihydro-1H-imidazo[1,5-c][1,3]thiazole-5,7-dione
• 化学式: C₁₉H₂₅N₃O₃S
• 分子量: 375.492
• InChiKey: APPZMJDNMFQDTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  87.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-{4-[(3,4-dihydro-2H-chromen-2-ylmethyl)amino]butyl}-1H-imidazo[1,5-c][1,3]thiazole-5,7(6H,7aH)-dione 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 6-{4-[(3,4-dihydro-2H-chromen-2-ylmethyl)amino]butyl}-1H-imidazo[1,5-c][1,3]thiazole-5,7(6H,7aH)-dione hydrochloride
  参考文献：
  名称：

  New Serotonin 5-HT_1A Receptor Agonists with Neuroprotective Effect against Ischemic Cell Damage

  摘要：

  We report the synthesis of new compounds 4 35 based on structural modifications of different moieties of previously described lead UCM-2550. The new nonpiperazine derivatives, representing second-generation agonists, were assessed for binding affinity, selectivity, and functional activity at the 5-HT1A receptor (5-HT1AR). Computational beta(2)-based homology models of the ligand receptor complexes were used to explain the observed structure affinity relationships. Selected candidates were also evaluated for their potential in vitro and in vivo neuroprotective properties. Interestingly, compound 26 (2-{6-[(3,4:-dihydro-2H-chromen-2-ylmethyl)amino]hexyl}-tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione) has been characterized as a high-affinity and potent 5-HT1AR agonist (K-i, = 5.9 nM, EC50 = 21.8 nM) and exhibits neuroprotective effect in neurotoxicity assays in primary cell cultures from rat hippocampus and in the MCAO model of focal cerebral ischemia in rats.

  DOI：

  10.1021/jm2007886
• 作为产物：
  描述：

  l-perhydroimidazo<1,5-c>thiazole-5,7-dione 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 4.0h， 生成 6-{4-[(3,4-dihydro-2H-chromen-2-ylmethyl)amino]butyl}-1H-imidazo[1,5-c][1,3]thiazole-5,7(6H,7aH)-dione
  参考文献：
  名称：

  New Serotonin 5-HT_1A Receptor Agonists with Neuroprotective Effect against Ischemic Cell Damage

  摘要：

  We report the synthesis of new compounds 4 35 based on structural modifications of different moieties of previously described lead UCM-2550. The new nonpiperazine derivatives, representing second-generation agonists, were assessed for binding affinity, selectivity, and functional activity at the 5-HT1A receptor (5-HT1AR). Computational beta(2)-based homology models of the ligand receptor complexes were used to explain the observed structure affinity relationships. Selected candidates were also evaluated for their potential in vitro and in vivo neuroprotective properties. Interestingly, compound 26 (2-{6-[(3,4:-dihydro-2H-chromen-2-ylmethyl)amino]hexyl}-tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione) has been characterized as a high-affinity and potent 5-HT1AR agonist (K-i, = 5.9 nM, EC50 = 21.8 nM) and exhibits neuroprotective effect in neurotoxicity assays in primary cell cultures from rat hippocampus and in the MCAO model of focal cerebral ischemia in rats.

  DOI：

  10.1021/jm2007886

文献信息

• [EN] METHODS FOR PREVENTING AND/OR TREATING PAIN AND/OR MIGRAINE<br/>[FR] PROCÉDÉS POUR PRÉVENIR ET/OU TRAITER LA DOULEUR ET/OU LA MIGRAINE
  申请人：SCHWARZ PHARMA S L

  公开号：WO2008015538A2

  公开（公告）日：2008-02-07

  [EN] The present invention relates to methods for preventing and/or treating pain and/or migraine in a subject in need of such prevention and/or treatment. These methods comprise administering to the subject a diaza- and thiaza- cycloalkanedione compound, an isomer of the compound, or a hydrate, solvate, or salt of the compound or isomer.
  [FR] La présente invention concerne des procédés pour prévenir et/ou traiter la douleur et/ou la migraine chez un sujet ayant besoin d'une telle prévention et/ou d'un tel traitement. Ces procédés consistent à administrer au sujet un composé de diaza- et thiaza- cycloalcanedione, un isomère du composé, ou un hydrate, un solvate ou un sel du composé ou de l'isomère.