10-methyl-11-oxo-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxylic acid | 656816-30-7

• 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: 10-methyl-11-oxo-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxylic acid
• 英文别名: 5-methyl-6-oxobenzo[b][1,4]benzothiazepine-3-carboxylic acid
• CAS: 656816-30-7
• 化学式: C₁₅H₁₁NO₃S
• mdl: MFCD03450564
• 分子量: 285.323
• InChiKey: YPKRTLLXHVVFNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  82.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  10-methyl-11-oxo-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxylic acid 在 4-二甲氨基吡啶 、 双氧水 、 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 8.0h， 生成 10-methyl-11-oxo-N-phenyl-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
• 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 sodium hydride 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 10-methyl-11-oxo-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxylic acid
  参考文献：
  名称：

  [EN] 11-OXO-10,11-DIHYDRODIBENZO[B,F][1,4]THIAZEPINE S-OXIDE DERIVATIVES AND THEIR USE AS DOPAMINE D2 RECEPTOR ANTAGONISTS
  [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

  摘要：

  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。

  公开号：

  WO2015017412A1

文献信息

• [EN] HEPATITIS B CORE PROTEIN ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES DES PROTÉINES DU NOYAU DE L'HÉPATITE B
  申请人：UNIV INDIANA RES & TECH CORP

  公开号：WO2015138895A1

  公开（公告）日：2015-09-17

  ABSTRACT The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.

  摘要 本公开提供了部分具有对乙型肝炎病毒Cp具有变构效应的化合物。本文还提供了治疗病毒感染（如乙型肝炎）的方法，包括向需要的患者施用所述化合物。
• 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。
• Hepatitis B core protein allosteric modulators
  申请人：Indiana University Research and Technology Corporation

  公开号：US10183936B2

  公开（公告）日：2019-01-22

  The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.

  本公开内容部分提供了对乙型肝炎病毒 Cp 具有异生效应特性的化合物。本文还提供了治疗病毒感染（如乙型肝炎）的方法，包括向有需要的患者施用所公开的化合物。
• HEPATITIS B CORE PROTEIN ALLOSTERIC MODULATORS
  申请人：Indiana University Research and Technology Corporation

  公开号：EP3116316B1

  公开（公告）日：2019-07-10
• US9550742B2
  申请人：——

  公开号：US9550742B2

  公开（公告）日：2017-01-24