5,6-difluoro-2-(methylthio)benzothiazole | 1163123-55-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 5,6-difluoro-2-(methylthio)benzothiazole
• 英文别名: 5,6-difluoro-2-methylsulfanyl-benzothiazole；5,6-Difluoro-2-(methylsulfanyl)-1,3-benzothiazole；5,6-difluoro-2-methylsulfanyl-1,3-benzothiazole
• CAS: 1163123-55-4
• 化学式: C₈H₅F₂NS₂
• 分子量: 217.263
• InChiKey: RZYQYRYPIDQSSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  66.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5,6-difluoro-2-(methylthio)benzothiazole 在 Oxone 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 以50.6%的产率得到rac-5,6-difluoro-2-methanesulfinyl-benzothiazole
  参考文献：
  名称：

  HETEROARYL DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS

  摘要：

  本发明涉及以下公式的化合物，其中Ar，Het，R1和n的定义如本文所述，并且涉及适用于药物的酸盐、光学纯对映体、拉氏体或其二对映异构体混合物。公式I的化合物是促进睡眠激素受体拮抗剂，可用于治疗睡眠呼吸暂停症、嗜睡症、失眠、睡眠障碍、时差综合症、昼夜节律紊乱和与神经系统疾病相关的睡眠障碍。

  公开号：

  US20090163485A1
• 作为产物：
  描述：

  2,4,5-三氟苯胺 在 ammonium hydroxide 、 sodium hypochlorite 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.75h， 生成 5,6-difluoro-2-(methylthio)benzothiazole
  参考文献：
  名称：

  Water Networks Contribute to Enthalpy/Entropy Compensation in Protein–Ligand Binding

  摘要：

  The mechanism (or mechanisms) of enthalpy-entropy (HIS) compensation in protein ligand binding remains controversial, and there are still no predictive models (theoretical or experimental) in which hypotheses of ligand binding can be readily tested. Here we describe a particularly well-defined system of protein and ligands-human carbonic anhydrase (HCA) and a series of benzothiazole sulfonamide ligands with different patterns of fluorination-that we use to define enthalpy/entropy (HIS) compensation in this system thermodynamically and structurally. The binding affinities of these ligands (with the exception of one ligand, in which the deviation is understood) to HCA are, despite differences in fluorination pattern, indistinguishable; they nonetheless reflect significant and compensating changes in enthalpy and entropy of binding. Analysis reveals that differences in the structure and thermodynamic properties of the waters surrounding the bound ligands are an important contributor to the observed H/S compensation. These results support the hypothesis that the molecules of water filling the active site of a protein, and surrounding the ligand, are as important as the contact interactions between the protein and the ligand for biomolecular recognition, and in determining the thermodynamics of binding.

  DOI：

  10.1021/ja4075776

文献信息

• Heteroaryl derivatives as orexin receptor antagonists
  申请人：Hoffmann-La Roche Inc.

  公开号：US07897627B2

  公开（公告）日：2011-03-01

  The present invention relates to compounds of formula wherein Ar, Het, R1 and n are as defined herein and to pharmaceutically suitable acid addition salts, optically pure enantiomers, racemates or diastereomeric mixtures thereof. Compounds of formula I are orexin receptor antagonists and are useful in the treatment of sleep apnea, narcolepsy, insomnia, parasomnia, jet lag syndrome, circadian rhythms disorder and sleep disorders associated with neurological diseases.

  本发明涉及式I的化合物，其中Ar，Het，R1和n的定义如本文所述，以及药学上适宜的酸盐加成物，光学纯对映体，外消旋体或其间异构体混合物。式I的化合物是促进睡眠的受体拮抗剂，可用于治疗睡眠呼吸暂停症，嗜睡症，失眠症，睡眠障碍，时差综合症，昼夜节律紊乱和与神经系统疾病相关的睡眠障碍。
• Novel KCNQ2/Q3 Agonists as Potential Therapeutics for Epilepsy and Neuropathic Pain
  作者：Paul C. Fritch、Grant McNaughton-Smith、George S. Amato、James F. Burns、C. Wesley Eargle、Rosemarie Roeloffs、William Harrison、Leslie Jones、Alan D. Wickenden

  DOI：10.1021/jm901497b

  日期：2010.1.28

  Current drugs for the treatment of seizure disorders, although effective in many patients, still suffer from a number of failures and are not effective in some forms of resistant epilepsies. Historically, many of these drugs have multiple mechanisms of action including calcium and sodium channel blockade as well as GABAergic activity and thus a number of associated side effects. Modulation of the M-current through opening of KCNQ channels has been proposed as a way to attenuate neuroexcitability and have a therapeutic benefit for the treatment Of seizure disorders. Therefore, as part Of our program to identify new treatments for epilepsy, we set out to identify agonists of KCNQ channels. High throughput screening of our corporate collection led to the identification of 1, adamantane-1-carboxylic acid (3-methyl-3H-benzothiazol-2-ylidine) hydrazide, a potent KCNQ2/Q3 agonist. Herein, we describe the syntheses and structure-activity relationships of analogues of I its well as their in vivo activity in animal models of epilepsy and neuropathic pain.
• US7897627B2
  申请人：——

  公开号：US7897627B2

  公开（公告）日：2011-03-01
• [EN] HETEROARYL DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS HÉTÉROARYLES EN TANT QU'ANTAGONISTES DU RÉCEPTEUR À OREXINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009080533A1

  公开（公告）日：2009-07-02

  The present invention relates to compounds of Formula (I), wherein Ar is an unsubstituted or substituted aryl or heteroaryl group, wherein the aryl and the heteroaryl group may be substituted by one or more substituents R2; R2 is hydroxy, halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, C(O)-lower alkyl, nitro, NR,R,,, cyano, S-lower alkyl, SO2-lower alkyl, cycloalkyl, heterocycloalkyl, phenyloxy, benzyloxy, phenyl, NH-phenyl or heteroaryl, wherein the phenyl and heteroaryl group is unsubstituted or substituted by one or more substituents selected from lower alkyl or halogen; R,/R,, are independently from each other hydrogen or lower alkyl; R1 is hydrogen or lower alkyl; Het is a heteroaryl group, unsubstituted or substituted by one or more substituents selected from R3; R3 is hydroxy, halogen, =O, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, phenyl, lower alkoxy substituted by halogen, nitro, cyano, SO2-lower alkyl, cycloalkyl or heterocycloalkyl; n is 1 or 2; or to pharmaceutically suitable acid addition salts, optically pure enantiomers, racemates or diastereomeric mixtures thereof. It has been found that the compounds of formula (I) are orexin receptor antagonists and the related compounds may be useful in the treatment of sleep apnea, narcolepsy, insomnia, parasomnia, jet lag syndrome, circadian rhythms disorder or sleep disorders associated with neurological diseases.
• Water Networks Contribute to Enthalpy/Entropy Compensation in Protein–Ligand Binding
  作者：Benjamin Breiten、Matthew R. Lockett、Woody Sherman、Shuji Fujita、Mohammad Al-Sayah、Heiko Lange、Carleen M. Bowers、Annie Heroux、Goran Krilov、George M. Whitesides

  DOI：10.1021/ja4075776

  日期：2013.10.16

  The mechanism (or mechanisms) of enthalpy-entropy (HIS) compensation in protein ligand binding remains controversial, and there are still no predictive models (theoretical or experimental) in which hypotheses of ligand binding can be readily tested. Here we describe a particularly well-defined system of protein and ligands-human carbonic anhydrase (HCA) and a series of benzothiazole sulfonamide ligands with different patterns of fluorination-that we use to define enthalpy/entropy (HIS) compensation in this system thermodynamically and structurally. The binding affinities of these ligands (with the exception of one ligand, in which the deviation is understood) to HCA are, despite differences in fluorination pattern, indistinguishable; they nonetheless reflect significant and compensating changes in enthalpy and entropy of binding. Analysis reveals that differences in the structure and thermodynamic properties of the waters surrounding the bound ligands are an important contributor to the observed H/S compensation. These results support the hypothesis that the molecules of water filling the active site of a protein, and surrounding the ligand, are as important as the contact interactions between the protein and the ligand for biomolecular recognition, and in determining the thermodynamics of binding.