6-氨基-1,2-苯并异恶唑 | 828300-70-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并异恶唑
• 中文名称: 6-氨基-1,2-苯并异恶唑
• 中文别名: 6-氨基苯并异恶唑；6-氨基-1,2-苯异噁唑
• 英文名称: 6-aminobenzisoxazole
• 英文别名: benzo[d]isoxazol-6-yl-amine；6-aminobenzoisoxazole；6-Amino-1,2-benzisoxazole；1,2-benzoxazol-6-amine
• CAS: 828300-70-5
• 化学式: C₇H₆N₂O
• mdl: MFCD06659641
• 分子量: 134.137
• InChiKey: PWLPLUATWXICAC-UHFFFAOYSA-N

物化性质

• 沸点：
  311.6±15.0 °C(Predicted)
• 密度：
  1.317±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  52
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  6-氨基-1,2-苯并异恶唑 、 6,8-二溴咪唑并[1,2-a]吡嗪 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 16.0h， 生成 benzo[d]isoxazol-6-yl-(6-bromo-imidazo[1,2-a]pyrazin-8-yl)-amine
  参考文献：
  名称：

  [EN] CERTAIN HETEROCYCLIC SUBSTITUTED IMIDAZO[1,2-A]PYRAZIN-8-YLAMINES AND METHODS OF INHIBITION OF BRUTON'S TYROSINE KINASE BY SUCH COMPOUNDS
  [FR] CERTAINES IMIDAZO[1,2-A]PYRAZIN-8-YLAMINES SUBSTITUEES HETEROCYCLIQUES ET METHODES D'INHIBITION DE LA TYROSINE KINASE DE BRUTON UTILISANT CES COMPOSES

  摘要：

  公式(I)的化合物及其所有药物可接受的形态在此描述。公式I中所示的变量R1、R2、R3、Z2和Q在此定义。提供含有公式I的一个或多个化合物，或此类化合物的药物可接受的形态，以及一个或多个药物可接受的载体、辅料或稀释剂的药物组合物。还提供了治疗对抑制酪氨酸激酶活性有反应的某些疾病患者的方法。在某些实施例中，这些疾病对抑制Btk活性和/或B细胞增殖有反应。这些方法包括向患者给药公式I的化合物，以减少疾病的迹象或症状。这些疾病包括癌症、自身免疫和/或炎症性疾病，或急性炎症反应。因此，治疗方法包括给药足够量的本处提供的化合物或盐，以减少这些疾病的症状或减缓这些疾病的进展。其他实施例包括治疗其他动物的方法，包括家畜和驯养的伴侣动物，这些动物患有一种对抑制激酶活性有反应的疾病。治疗方法包括将公式I的化合物作为单一活性剂给药，或将公式I的化合物与一个或多个其他治疗剂组合给药。一种用于确定样本中Btk存在的方法，包括在允许检测Btk活性的条件下将样本与公式I的化合物或其形态接触，检测样本中的Btk活性水平，并据此确定样本中Btk的存在或不存在。

  公开号：

  WO2005005429A1
• 作为产物：
  描述：

  6-硝基-1,2-苯异噁唑 在 盐酸 、 四氯化锡 、 tin(ll) chloride 作用下， 反应 5.0h， 以55%的产率得到6-氨基-1,2-苯并异恶唑
  参考文献：
  名称：

  Toward bifunctional antibody catalysis

  摘要：

  Antibodies that catalyze the deprotonation of unactivated benzisoxazoles to give the corresponding salicylonitriles were prepared using as antigen a 2-aminobenzimidazolium derivative coupled to a carrier protein via its benzene ring. The hapten was designed to induce an antibody binding site with both a base and an acid, in position to initiate proton transfer and stabilize developing negative charge at the phenoxide leaving group, respectively. Consistent with this design, the catalysts exhibit bell-shaped pH-rate profiles, while chemical modification identified several functional groups that could participate in bifunctional catalysis. One of the antibodies, 13G5, is particularly notable in catalyzing the elimination of 6-glutaramidebenzisoxazole with a > 10(5)-fold rate acceleration over background and an effective molarity of > 10(4) M for its catalytic base. These properties compare favorably to the efficiencies achieved by the best previously characterized antibodies with substantially more reactive substrates. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.05.071

文献信息

• [EN] PIPERIDINE/CYCLOHEXANE CARBOXAMIDE DERIVATIVES FOR USE AS VANILLOID RECEPTOR MODULATORS<br/>[FR] DERIVES CARBOXAMIDES DE PIPERIDINE/CYCLOHEXANE DESTINES A ETRE UTILISES COMME MODULATEURS DU RECEPTEUR VANILLOIDE
  申请人：GLAXO GROUP LTD

  公开号：WO2005016915A1

  公开（公告）日：2005-02-24

  Certain compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, P, P', X, m and n are as defined in the specification, a process for preparing such compounds, a pharmaceutical composition comprising such compounds and the use of such compounds in medicine, as vanilloid receptor modulators.

  某些式（I）化合物，或其药学上可接受的盐或溶剂合物，其中R1、R2、P、P'、X、m和n如说明书中所定义，制备此类化合物的方法，包含此类化合物的药物组合物，以及此类化合物在医学中作为香草素受体调节剂的用途。
• [EN] NOVEL KINASE INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2014060113A1

  公开（公告）日：2014-04-24

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种具有公式（I）的新化合物，能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体。这些化合物在治疗多种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和激素相关疾病。
• [EN] PYRAZOLO[4,3-D]PYRIMIDINES AS KINASE INHIBITORS<br/>[FR] PYRAZOLO[4,3-D]PYRIMIDINES UTILES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2014060112A1

  公开（公告）日：2014-04-24

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及具有式（I）的新化合物，其能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体。这些化合物可用于治疗多种疾病。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和激素相关疾病。
• Certain heterocyclic substituted imidazo[1,2-A]pyrazin-8-ylamines and methods of inhibition of bruton's tyrosine kinase by such compounds
  申请人：Currie S. Kevin

  公开号：US20050101604A1

  公开（公告）日：2005-05-12

  Compounds of Formula I and all pharmaceutically acceptable forms thereof, are described herein. The variables R 1 , R 2 , R 3 , Z 2 , and Q, shown in Formula I are defined herein. Pharmaceutical compositions containing one or more compounds of Formula I, or a pharmaceutically acceptable form of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein. Methods of treating patients suffering from certain diseases responsive to inhibition of tyrosine kinase activity are also given. In certain embodiments the diseases are responsive to inhibition of Btk activity and/or B-cell proliferation. Such methods comprise administering to such patients an amount of a compound of Formula I effective to reduce signs or symptoms of the disease. These diseases include cancer, an autoimmune and/or inflammatory disease, or an acute inflammatory reaction. Thus methods of treatment include administering a sufficient amount of a compound or salt as provided herein to decrease the symptoms or slow the progression of these diseases. Other embodiments include methods of treating other animals, including livestock and domesticated companion animals, suffering from a disease responsive to inhibition of kinase activity. Methods of treatment include administering a compound of Formula I as a single active agent or administering a compound of Formula I in combination with one or more other therapeutic agent. A method for determining the presence of Btk in a sample, comprising contacting the sample with a compound or form thereof of Formula I under conditions that permit detection of Btk activity, detecting a level of Btk activity in the sample, and therefrom determining the presence or absence of Btk in the sample.

  本文描述了公式I的化合物及其所有药学上可接受的形式。公式I中所示的变量R1、R2、R3、Z2和Q在此定义。本文提供了含有一个或多个公式I化合物或其药学上可接受的形式以及一个或多个药学上可接受的载体、辅料或稀释剂的制药组合物。本文还提供了治疗对酪氨酸激酶活性抑制具有响应的某些疾病的方法。在某些实施例中，这些疾病对Btk活性和/或B细胞增殖的抑制具有响应。这些方法包括向这些患者施用足够量的公式I化合物，以减少疾病的体征或症状。这些疾病包括癌症、自身免疫和/或炎症性疾病或急性炎症反应。因此，治疗方法包括向患者施用足够量的公式或盐，以减轻这些疾病的症状或减缓其进展。其他实施例包括治疗其他动物，包括家畜和驯养的伴侣动物，患有对激酶活性抑制具有响应的疾病。治疗方法包括将公式I化合物作为单一活性剂或与一个或多个其他治疗剂联合使用。一种用于确定样品中Btk存在的方法，包括在允许检测Btk活性的条件下，将样品与公式I化合物或其形式接触，检测样品中Btk活性的水平，并据此确定样品中Btk的存在或不存在。
• Certain Heterocyclic Substituted Imidazo[1,2-A]Pyrazin-8-Ylamines And Methods Of Inhibition Of Bruton's Tyrosine Kinase By Such Compounds
  申请人：CURRIE Kevin S.

  公开号：US20080182849A1

  公开（公告）日：2008-07-31

  Compounds of Formula I and all pharmaceutically acceptable forms thereof, are described herein. The variables R 1 , R 2 , R 3 , Z 2 , and Q, shown in Formula I are defined herein. Pharmaceutical compositions containing one or more compounds of Formula I, or a pharmaceutically acceptable form of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein. Methods of treating patients suffering from certain diseases responsive to inhibition of tyrosine kinase activity are also given. In certain embodiments the diseases are responsive to inhibition of Btk activity and/or B-cell proliferation. Such methods comprise administering to such patients an amount of a compound of Formula I effective to reduce signs or symptoms of the disease. These diseases include cancer, an autoimmune and/or inflammatory disease, or an acute inflammatory reaction. Thus methods of treatment include administering a sufficient amount of a compound or salt as provided herein to decrease the symptoms or slow the progression of these diseases. Other embodiments include methods of treating other animals, including livestock aid domesticated companion animals, suffering from a disease responsive to inhibition of kinase activity. Methods of treatment include administering a compound of Formula I as a single active agent or administering a compound of Formula I in combination with one or more other therapeutic agent. A method for determining the presence of Btk in a sample, comprising contacting the sample with a compound or form thereof of Formula I under conditions that permit detection of Btk activity, detecting a level of Btk activity in the sample, and therefrom determining the presence or absence of Btk in the sample.

  本文描述了公式I的化合物及其所有药用可接受形式。公式I中所示的变量R1、R2、R3、Z2和Q在此定义。本文提供了含有一个或多个公式I化合物或药用可接受形式以及一个或多个药用可接受载体、辅料或稀释剂的制药组合物。本文还提供了治疗对酪氨酸激酶活性抑制有反应的某些疾病的方法。在某些实施例中，这些疾病对Btk活性和/或B细胞增殖的抑制有反应。这些方法包括向这些患者施用足够的公式I化合物的量，以减少疾病的症状或症候。这些疾病包括癌症、自身免疫和/或炎症性疾病或急性炎症反应。因此，治疗方法包括向患者施用足够的公式或盐，以减轻这些疾病的症状或减缓其进展。其他实施例包括治疗其他动物，包括家畜和驯养的伴侣动物，患有对激酶活性抑制有反应的疾病的方法。治疗方法包括将公式I化合物作为单一活性剂或与一个或多个其他治疗剂联合使用。一种用于确定样品中Btk存在的方法，包括将样品与公式I化合物或其形式接触，以便在允许检测Btk活性的条件下检测样品中的Btk活性，并从中确定样品中Btk的存在或不存在。