benzo[d]thiazol-2-yl(4-hydroxyphenyl)methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: benzo[d]thiazol-2-yl(4-hydroxyphenyl)methanone
• 英文别名: benzothiazol-2-yl-(4-hydroxy-phenyl)methanone；2-(4-Hydroxybenzoyl)benzothiazole；1,3-benzothiazol-2-yl-(4-hydroxyphenyl)methanone
• 化学式: C₁₄H₉NO₂S
• 分子量: 255.297
• InChiKey: AFSAQBCWILOUKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzo[d]thiazol-2-yl(4-hydroxyphenyl)methanone 在 caesium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 8.0h， 生成 benzo[d]thiazol-2-yl(4-(3-morpholinopyrazin-2-yloxy)phenyl)methanone
  参考文献：
  名称：

  Design, Optimization, and Biological Evaluation of Novel Keto-Benzimidazoles as Potent and Selective Inhibitors of Phosphodiesterase 10A (PDE10A)

  摘要：

  Our development of PDE10A inhibitors began with an HTS screening hit (1) that exhibited both high p-glycoprotein (P-gp) efflux ratios in rat and human and poor metabolic stability. On the basis of cocrystal structure of 1 in human PDE10A enzyme, we designed a novel keto-benzimidazole 26 with comparable PDE10A potency devoid of efflux liabilities. On target in vivo coverage of PDE10A in rat brain was assessed using our previously reported LC-MS/MS receptor occupancy (RO) technology. Compound 26 achieved 55% RO of PDE10A at 30 mg/kg po and covered PDE10A receptors in rat brain in a dose-dependent manner. Cocrystal structure of 26 in PDE10A confirmed the binding mode of the novel scaffold. Further optimization resulted in the identification of keto-benzimidazole 34, which showed an increased in vivo efficacy of 57% RO in rats at 10 mg/kg po and an improved in vivo rat clearance and oral bioavailability.

  DOI：

  10.1021/jm401234w
• 作为产物：
  描述：

  benzothiazol-2-yl-(4-benzyloxy-phenyl)methanone 在 二甲基硫 、 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 以72%的产率得到benzo[d]thiazol-2-yl(4-hydroxyphenyl)methanone
  参考文献：
  名称：

  [EN] PYRAZINE COMPOUNDS AS PHOSPHODIESTERASE 10 INHIBITORS
  [FR] COMPOSES DE PYRAZINE COMME INHIBITEURS DE PHOSPHODIESTERASE 10

  摘要：

  吡嗪化合物、含有它们的组合物以及制备这些化合物的方法。还提供了通过抑制PDE10治疗可治疗的疾病或病症的方法，例如肥胖、非胰岛素依赖型糖尿病、精神分裂症、双相情感障碍、强迫症等。

  公开号：

  WO2010057121A1

文献信息

• I2 promoted domino oxidative cyclization for one-pot synthesis of 2-acylbenzothiazoles via metal-free sp3 C–H functionalization
  作者：Yan-Ping Zhu、Mi Lian、Feng-Cheng Jia、Mei-Cai Liu、Jing-Jing Yuan、Qing-He Gao、An-Xin Wu

  DOI：10.1039/c2cc34561g

  日期：——

  An I(2) promoted domino protocol was developed to construct 2-acylbenzothiazoles from simple and readily available aromatic ketones/unsaturated methyl ketones and o-aminobenzenethiols. The reaction proceeded smoothly under metal-free and peroxide-free conditions.

  一个I（2）促进多米诺协议被开发，构建从简单的2 acylbenzothiazoles和容易获得的芳族酮/不饱和的甲基酮和邻 - aminobenzenethiols。该反应的金属和无过氧化物的条件下顺利进行。
• A Novel Self-Sequence Reaction Network Involving a Set of Six Reactions in One Pot: The Synthesis of Substituted Benzothiazoles from Aromatic Ketones and Anilines
  作者：Wei-Jian Xue、Ya-Qiong Guo、Fang-Fang Gao、Hong-Zheng Li、An-Xin Wu

  DOI：10.1021/ol400029t

  日期：2013.2.15

  and readily available aromatic ketones and anilines as starting materials resulted in the construction of 2-acylbenzothiazoles via a novel self-sequence reaction network, which assembles six reactions in one pot. The reaction network not only supplied a novel method for constructing complex molecules but also provided a typical example for logical self-organization synthesis.

  使用简单易得的芳香族酮和苯胺作为起始原料，可以通过一个新颖的自序反应网络构建2-酰基苯并噻唑，该网络在一个罐中组装六个反应。该反应网络不仅为构建复杂分子提供了一种新颖的方法，而且为逻辑自组织合成提供了一个典型的例子。
• Pyrazine compounds as phosphodiesterase 10 inhibitors
  申请人：Amgen Inc.

  公开号：US08053438B2

  公开（公告）日：2011-11-08

  Pyrazine compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

  本文提供了吡嗪化合物及含有它们的组合物以及制备这些化合物的方法。此外，本文还提供了治疗PDE10抑制剂可治疗的疾病或疾病的方法，例如肥胖症、非胰岛素依赖性糖尿病、精神分裂症、躁郁症、强迫症等。
• PYRAZINE COMPOUNDS AS PHOSPHODIESTERASE 10 INHIBITORS
  申请人：Allen Jennifer R.

  公开号：US20110160182A1

  公开（公告）日：2011-06-30

  Pyrazine compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

  本发明提供了吡嗪化合物、含有它们的组合物以及制备这些化合物的方法。本发明还提供了治疗通过抑制PDE10可治疗的疾病或疾病的方法，例如肥胖症、非胰岛素依赖性糖尿病、精神分裂症、双相障碍、强迫症等。
• Benzothiazole derivatives
  申请人：NIPPON ZOKI PHARMACEUTICAL CO., LTD.

  公开号：EP0735029A1

  公开（公告）日：1996-10-02

  The object of the present invention is to provide novel benzothiazole derivatives and pharmaceutically acceptable salts thereof, which have a lipid lowering activity and are useful as a medicine. The compounds of the present invention and pharmaceutically acceptable salts thereof are represented by the following formula (I): wherein R1 is halogen, alkyl, trifluoromethyl, acetamide or -OX1; X1 is hydrogen, alkyl or acyl; R2 is hydrogen, halogen, alkyl, hydroxyalkyl, trifluoromethyl, nitro, amino which may be substituted with alkyl or acyl, carboxy which may be esterified with alkyl, or -OX2; X2 is hydrogen, alkyl, acyl, carboxyalkyl which may be esterified with alkyl; or n is an integer from 1 to 3 which means a number of substituent R2; and plural R2 may be the same or different when n is 2 or 3; with the proviso that R1 is a group other than chloride when R2 is hydrogen. The benzothiazole derivatives of the present invention have excellent pharmacological activities which significantly decrease cholesterol, triglyceride and low-density lipoprotein in blood. Therefore, they are novel compounds which are very useful as medicines such as a remedy for hyperlipemia.

  本发明的目的是提供新型苯并噻唑衍生物及其药学上可接受的盐类，它们具有降血脂活性并可用作药物。 本发明的化合物及其药学上可接受的盐由下式（I）表示： 其中 R1 是卤素、烷基、三氟甲基、乙酰胺或-OX1； X1 是氢、烷基或酰基； R2 是氢、卤素、烷基、羟烷基、三氟甲基、硝基、可被烷基或酰基取代的氨基、可被烷基酯化的羧基或-OX2； X2 是氢、烷基、酰基、可与烷基酯化的羧基； 或 n 是 1 至 3 的整数，表示取代基 R2 的数目； 当 n 为 2 或 3 时，多个 R2 可以相同或不同；但当 R2 为氢时，R1 为氯以外的基团。 本发明的苯并噻唑衍生物具有良好的药理活性，可显著降低血液中的胆固醇、甘油三酯和低密度脂蛋白。因此，它们是非常有用的新型化合物，可用作药物，如治疗高脂血症。