N-(4-methoxybenzyl)-11-oxo-10-propyl-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide 5-oxide | 1596117-46-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: N-(4-methoxybenzyl)-11-oxo-10-propyl-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide 5-oxide
• 英文别名: N-[(4-methoxyphenyl)methyl]-6,11-dioxo-5-propylbenzo[b][1,4]benzothiazepine-3-carboxamide
• CAS: 1596117-46-2
• 化学式: C₂₅H₂₄N₂O₄S
• 分子量: 448.543
• InChiKey: WXTCFMURJMFQKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  94.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  11-氧代-10,11-二氢二苯并[B,F][1,4]硫氮杂-8-羧酸 在 4-二甲氨基吡啶 、 双氧水 、 sodium hydride 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.5h， 生成 N-(4-methoxybenzyl)-11-oxo-10-propyl-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide 5-oxide
  参考文献：
  名称：

  Discovery, Optimization, and Characterization of Novel D₂ Dopamine Receptor Selective Antagonists

  摘要：

  The D2 dopamine receptor (D2 DAR) is one of the most validated drug targets for neuropsychiatric and endocrine disorders. However, clinically approved drugs targeting 02 DAR display poor selectivity between the D2 and other receptors, especially the D3 DAR This lack of selectivity may lead to undesirable side effects. Here we describe the chemical and pharmacological characterization of a novel 02 DAR antagonist series with excellent D2 versus D1, D3, D4, and D5 receptor selectivity. The final probe 65 was obtained through a quantitative high-throughput screening campaign, followed by medicinal chemistry optimization, to yield a selective molecule with good in vitro physical properties, metabolic stability, and in vivo pharmacokinetics. The optimized molecule may be a useful in vivo probe for studying D2 DAR signal modulation and could also serve as a lead compound for the development of D2 DAR-selective druglike molecules for the treatment of multiple neuropsychiatric and endocrine disorders.

  DOI：

  10.1021/jm500126s

文献信息

• [EN] 11-OXO-10,11-DIHYDRODIBENZO[B,F][1,4]THIAZEPINE S-OXIDE DERIVATIVES AND THEIR USE AS DOPAMINE D2 RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS DE 11-OXO-10,11-DIHYDRODIBENZO[B,F][1,4]THIAZÉPINE S-OXYDE ET LEUR UTILISATION COMME ANTAGONISTES DU RÉCEPTEUR D2 DE LA DOPAMINE
  申请人：US HEALTH

  公开号：WO2015017412A1

  公开（公告）日：2015-02-05

  The disclosure includes compounds and pharmaceutically acceptable salts of Formula (I). Certain compounds and salts of Formula (I) are selective inhibitors of the Dopamine D2 receptor. The variables R1-R4, n, and L are defined herein. The disclosure also provides methods of synthesizing compounds of Formula (I) and pharmaceutical compositions containing compounds of Formula (I). Additionally the disclosure provides methods or treating patients suffering from central nervous system disorders, including Tourette's syndrome, bipolar disorder, hyperprolactinemia, tardive dyskinesia, Huntington's chorea, psychosis, depression, or schizophrenia.

  该披露包括公式（I）的化合物和药用盐。公式（I）的某些化合物和盐是多巴胺D2受体的选择性抑制剂。变量R1-R4、n和L在此有定义。该披露还提供了合成公式（I）化合物的方法和含有公式（I）化合物的药物组合物。此外，该披露提供了治疗患有中枢神经系统疾病的患者的方法，包括抽动症、躁郁症、高泌乳素血症、迟发性运动障碍、亨廷顿舞蹈症、精神病、抑郁症或精神分裂症。
• 11-OXO-10,11-DIHYDRODIBENZO[B,F][1,4]THIAZEPINE S-OXIDE DERIVATIVES AND THEIR USE AS DOPAMINE D2 RECEPTOR ANTAGONISTS
  申请人：THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN

  公开号：US20160176831A1

  公开（公告）日：2016-06-23

  The disclosure includes compounds and pharmaceutically acceptable salts of Formula (I). Certain compounds and salts of Formula (I) are selective inhibitors of the Dopamine D 2 receptor. The variables R 1 -R 4 , n, and L are defined herein. The disclosure also provides methods of synthesizing compounds of Formula (I) and pharmaceutical compositions containing compounds of Formula (I). Additionally the disclosure provides methods or treating patients suffering from central nervous system disorders, including Tourette's syndrome, bipolar disorder, hyperprolactinemia, tardive dyskinesia, Huntington's chorea, psychosis, depression, or schizophrenia.

  本公开涵盖公式（I）的化合物和药物可接受的盐。公式（I）的某些化合物和盐是多巴胺D2受体的选择性抑制剂。变量R1-R4，n和L在此定义。本公开还提供了合成公式（I）化合物和含有公式（I）化合物的制药组合物的方法。此外，本公开还提供了治疗患有中枢神经系统疾病的患者的方法，包括抽动症、躁郁症、高催乳素血症、迟发性运动障碍、亨廷顿舞蹈病、精神病、抑郁症或精神分裂症。
• US9550742B2
  申请人：——

  公开号：US9550742B2

  公开（公告）日：2017-01-24
• Discovery, Optimization, and Characterization of Novel D₂ Dopamine Receptor Selective Antagonists
  作者：Jingbo Xiao、R. Benjamin Free、Elena Barnaeva、Jennie L. Conroy、Trevor Doyle、Brittney Miller、Marthe Bryant-Genevier、Mercedes K. Taylor、Xin Hu、Andrés E. Dulcey、Noel Southall、Marc Ferrer、Steve Titus、Wei Zheng、David R. Sibley、Juan J. Marugan

  DOI：10.1021/jm500126s

  日期：2014.4.24

  The D2 dopamine receptor (D2 DAR) is one of the most validated drug targets for neuropsychiatric and endocrine disorders. However, clinically approved drugs targeting 02 DAR display poor selectivity between the D2 and other receptors, especially the D3 DAR This lack of selectivity may lead to undesirable side effects. Here we describe the chemical and pharmacological characterization of a novel 02 DAR antagonist series with excellent D2 versus D1, D3, D4, and D5 receptor selectivity. The final probe 65 was obtained through a quantitative high-throughput screening campaign, followed by medicinal chemistry optimization, to yield a selective molecule with good in vitro physical properties, metabolic stability, and in vivo pharmacokinetics. The optimized molecule may be a useful in vivo probe for studying D2 DAR signal modulation and could also serve as a lead compound for the development of D2 DAR-selective druglike molecules for the treatment of multiple neuropsychiatric and endocrine disorders.