3-(5,6-dimethyl-3-thia-1,4,7,8a-tetraaza-as-indacen-8-yl)benzamide | 1581780-54-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(5,6-dimethyl-3-thia-1,4,7,8a-tetraaza-as-indacen-8-yl)benzamide
• 英文别名: 3-(5,6-Dimethyl-3-thia-1,4,7,8a-tetraaza-as-indacen-8-yl)-benzamide；3-(8,10-dimethyl-5-thia-1,3,7,11-tetrazatricyclo[7.3.0.02,6]dodeca-2(6),3,7,9,11-pentaen-12-yl)benzamide
• CAS: 1581780-54-2
• 化学式: C₁₆H₁₃N₅OS
• 分子量: 323.378
• InChiKey: UKUKUXZDSNHMBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-噻唑-5-基-乙酰胺 在 N-溴代丁二酰亚胺(NBS) 、 copper(l) iodide 、 四磷十氧化物 、 (1R,2R)-(-)-N,N'-二甲基-1,2-环己二胺 、 溴 、 caesium carbonate 、 三氯氧磷 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 49.0h， 生成 3-(5,6-dimethyl-3-thia-1,4,7,8a-tetraaza-as-indacen-8-yl)benzamide
  参考文献：
  名称：

  新型，有效，选择性和脑渗透性磷酸二酯酶10A抑制剂。

  摘要：

  在本文中，我们报道了一系列新的磷酸二酯酶10A抑制剂的发现。优化HTS命中率（17）会产生有效的，选择性的和脑渗透剂23和26。二者均表现出低得多的体内清除率和减小的分布体积（大鼠PK），因此具有以比参考化合物WEB-3更低的有效剂量抑制体内PDE10A靶标的潜力。

  DOI：

  10.1016/j.bmcl.2018.12.029

文献信息

• [EN] NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A<br/>[FR] NOUVEAUX COMPOSÉS INHIBITEURS DE PHOSPHODIESTÉRASE DE TYPE 10A
  申请人：ABBOTT GMBH & CO KG

  公开号：WO2014041175A1

  公开（公告）日：2014-03-20

  The present invention relates to compounds of the formula I, the N-oxides, tautomers, the prodrugs and the pharmaceutically acceptable salts thereof. where in formula I the variables X, Y, Q1, Q2 have the following meanings: X is C-R3 or N; Q1 is S or O and Q2 is C-R4 or N and Q2 is connected to X via a double bond while Q1 is connected to X via a single bond; or Q2 is S or O and Q1 is C-R4 or N and Q1 is connected to X via a double bond while Q2 is connected to X via a single bond; Y is C-R5 or N; where in formula I the variables R1, R2, R3, R4 and R5 are as defined in the claims The compounds of the formula I, the N-oxides, tautomers, the prodrugs and the pharmaceutically acceptable salts thereof are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders.

  本发明涉及公式I的化合物，其N-氧化物、互变异构体、前药和其药学上可接受的盐。在公式I中，变量X、Y、Q1、Q2具有以下含义：X为C-R3或N；Q1为S或O，Q2为C-R4或N，Q2通过双键与X连接，而Q1通过单键与X连接；或者Q2为S或O，Q1为C-R4或N，Q1通过双键与X连接，而Q2通过单键与X连接；Y为C-R5或N；在公式I中，变量R1、R2、R3、R4和R5的定义如索权中所述。公式I的化合物、N-氧化物、互变异构体、前药和其药学上可接受的盐是磷酸二酯酶10A的抑制剂，用于制备药物，并因此适用于治疗或控制神经系统疾病和精神疾病，缓解与这些疾病相关的症状，并降低这些疾病的风险。
• NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A
  申请人：AbbVie Inc.

  公开号：US20140107126A1

  公开（公告）日：2014-04-17

  The present invention relates to compounds of the formula I, the N-oxides, tautomers, the prodrugs and the pharmaceutically acceptable salts thereof. where in formula I the variables X, Y, Q 1 , Q 2 have the following meanings: X is C—R 3 or N; Q 1 is S or O and Q 2 is C—R 4 or N and Q 2 is connected to X via a double bond while Q 1 is connected to X via a single bond; or Q 2 is S or O and Q 1 is C—R 4 or N and Q 1 is connected to X via a double bond while Q 2 is connected to X via a single bond; Y is C—R 5 or N; where in formula I the variables R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the claims The compounds of the formula I, the N-oxides, tautomers, the prodrugs and the pharmaceutically acceptable salts thereof are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders.

  本发明涉及公式I的化合物，其N-氧化物、互变异构体、前药及其药学上可接受的盐。在公式I中，变量X、Y、Q1、Q2具有以下含义：X为C—R3或N；Q1为S或O，Q2为C—R4或N，而Q2通过双键与X连接，Q1通过单键与X连接；或者Q2为S或O，Q1为C—R4或N，而Q1通过双键与X连接，Q2通过单键与X连接；Y为C—R5或N。在公式I中，变量R1、R2、R3、R4和R5如权利要求所定义。公式I的化合物、N-氧化物、互变异构体、前药及其药学上可接受的盐是磷酸二酯酶10A的抑制剂，用于制造药物，因此适用于治疗或控制神经系统疾病和精神疾病，改善与此类疾病相关的症状并降低此类疾病的风险。
• Inhibitor compounds of phosphodiesterase type 10A
  申请人：Abbott GmbH & Co. KG

  公开号：US09388180B2

  公开（公告）日：2016-07-12

  The present invention relates to compounds of the formula I, the N-oxides, tautomers, the prodrugs and the pharmaceutically acceptable salts thereof. where in formula I the variables X, Y, Q1, Q2 have the following meanings: X is C—R3 or N; Q1 is S or O and Q2 is C—R4 or N and Q2 is connected to X via a double bond while Q1 is connected to X via a single bond; or Q2 is S or O and Q1 is C—R4 or N and Q1 is connected to X via a double bond while Q2 is connected to X via a single bond; Y is C—R5 or N; where in formula I the variables R1, R2, R3, R4 and R5 are as defined in the claims The compounds of the formula I, the N-oxides, tautomers, the prodrugs and the pharmaceutically acceptable salts thereof are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders.

  本发明涉及公式I的化合物，其N-氧化物、互变异构体、前药和其药学上可接受的盐，其中公式I中的变量X、Y、Q1、Q2具有以下含义：X为C—R3或N；Q1为S或O，Q2为C—R4或N，且Q2通过双键与X连接，而Q1通过单键与X连接；或者Q2为S或O，Q1为C—R4或N，且Q1通过双键与X连接，而Q2通过单键与X连接；Y为C—R5或N；在公式I中，变量R1、R2、R3、R4和R5如权利要求所定义。公式I的化合物、N-氧化物、互变异构体、前药和其药学上可接受的盐是磷酸二酯酶10A的抑制剂，可用于制造药物，因此适用于治疗或控制神经系统和精神系统疾病，改善与此类疾病相关的症状并降低此类疾病的风险。
• US9388180B2
  申请人：——

  公开号：US9388180B2

  公开（公告）日：2016-07-12
• Novel, potent, selective, and brain penetrant phosphodiesterase 10A inhibitors
  作者：Hervé Geneste、Karla Drescher、Clarissa Jakob、Loïc Laplanche、Michael Ochse、Maricel Torrent

  DOI：10.1016/j.bmcl.2018.12.029

  日期：2019.2

  Herein we report the discovery of a novel series of phosphodiesterase 10A inhibitors. Optimization of a HTS hit (17) resulted in potent, selective, and brain penetrant 23 and 26; both exhibited much lower clearance in vivo and decreased volume of distribution (rat PK) and have thus the potential to inhibit the PDE10A target in vivo at a lower efficacious dose than the reference compound WEB-3.

  在本文中，我们报道了一系列新的磷酸二酯酶10A抑制剂的发现。优化HTS命中率（17）会产生有效的，选择性的和脑渗透剂23和26。二者均表现出低得多的体内清除率和减小的分布体积（大鼠PK），因此具有以比参考化合物WEB-3更低的有效剂量抑制体内PDE10A靶标的潜力。