4-bromo-2-hydrazinylbenzoic acid | 1232133-69-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-bromo-2-hydrazinylbenzoic acid
• 英文别名: 4-bromo-2-hydrazineylbenzoic acid
• CAS: 1232133-69-5
• 化学式: C₇H₇BrN₂O₂
• 分子量: 231.049
• InChiKey: DRQGPUIZIISGCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-bromo-2-hydrazinylbenzoic acid 在 ammonium hydroxide 、 1-羟基苯并三唑 、 1,2-二氯乙烷 作用下， 以 四氢呋喃 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 2.5h， 生成 ethyl 5-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate
  参考文献：
  名称：

  Small Molecule Reversible Inhibitors of Bruton’s Tyrosine Kinase (BTK): Structure–Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177)

  摘要：

  Bruton's tyrosine,kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous auto-immune diseases. This article will detail the structure-activity relationships (SARs) leading to a novel second generation series of potent and, selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oXo-3,4-dihydroquinazdlin-3-yl)phenyl]-9H-carbazole-1-carboxarnide 6 (BMS-935177) was selected:to advance into clinical development.

  DOI：

  10.1021/acs.jmedchem.6b00722
• 作为产物：
  描述：

  2-氨基-4-溴苯甲酸 在 盐酸 、 sodium nitrite 、 tin(II) chloride dihdyrate 作用下， 以 水 为溶剂， 反应 17.0h， 以15 g的产率得到4-bromo-2-hydrazinylbenzoic acid
  参考文献：
  名称：

  [EN] KINASE INHIBITORS
  [FR] INHIBITEURS DE KINASE

  摘要：

  本文披露了蛋白激酶抑制剂，特别是Bruton氏酪氨酸激酶（BTK）抑制剂，包括它们的制剂、制备过程以及利用这些蛋白激酶抑制剂治疗或预防与激酶功能相关的疾病、疾病和症状的用途。具体来说，本发明涉及选择性BTK抑制剂。

  公开号：

  WO2021207549A1

文献信息

• [EN] KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE
  申请人：GB005 INC

  公开号：WO2021207549A1

  公开（公告）日：2021-10-14

  Disclosed herein are protein kinase inhibitors, in particular Bruton's tyrosine kinase (BTK) inhibitors, pharmaceutical compositions comprising them, processes for preparing them and uses of such protein kinase inhibitors to treat or prevent diseases, disorders and conditions associated with kinase function. In particular, the present invention relates to selective BTK inhibitors.

  本文披露了蛋白激酶抑制剂，特别是Bruton氏酪氨酸激酶（BTK）抑制剂，包括它们的制剂、制备过程以及利用这些蛋白激酶抑制剂治疗或预防与激酶功能相关的疾病、疾病和症状的用途。具体来说，本发明涉及选择性BTK抑制剂。
• Conversion of carbazole carboxamide based reversible inhibitors of Bruton’s tyrosine kinase (BTK) into potent, selective irreversible inhibitors in the carbazole, tetrahydrocarbazole, and a new 2,3-dimethylindole series
  作者：Qingjie Liu、Douglas G. Batt、Charu Chaudhry、Jonathan S. Lippy、Mark A. Pattoli、Neha Surti、Songmei Xu、Percy H. Carter、James R. Burke、Joseph A. Tino

  DOI：10.1016/j.bmcl.2018.07.041

  日期：2018.10

  Incorporation of a suitably-placed electrophilic group transformed a series of reversible BTK inhibitors based on carbazole-1-carboxamide and tetrahydrocarbazole-1-carboxamide into potent, irreversible inhibitors. Removal of one ring from the core of these compounds provided a potent irreversible series of 2,3-dimethylindole-7-carboxamides having excellent potency and improved selectivity, with the

  适当放置的亲电基团的引入将基于咔唑-1-甲酰胺和四氢咔唑-1-甲酰胺的一系列可逆BTK抑制剂转化为有效的不可逆抑制剂。从这些化合物的核心上除去一个环，提供了一系列有效的不可逆的2,3-二甲基吲哚-7-羧酰胺，具有优异的效能和改进的选择性，并具有降低亲脂性和分子量的其他优点。
• SUBSTITUTED PYRAZOLOQUINAZOLINONES AND PYRROLOQUINAZOLINONES AS ALLOSTERIC MODULATORS OF GROUP II METABOTROPIC GLUTAMATE RECEPTORS
  申请人：Domain Therapeutics

  公开号：US20150105381A1

  公开（公告）日：2015-04-16

  The present invention relates to the pyrazoloquinazolinone and pyrroloquinazolinone derivatives of the general formula (I), as well as pharmaceutical compositions containing them, and their use in the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals, in particular their use in the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders.

  本发明涉及一般式(I)的吡唑喹唑酮和吡咯喹唑酮衍生物，以及包含它们的制药组合物，以及它们在治疗和/或预防与改变谷氨酸能信号和/或功能相关的疾病和/或在哺乳动物中可以受到谷氨酸水平或信号改变影响的疾病中的应用，特别是在治疗和/或预防急性和慢性神经和/或精神障碍方面的应用。
• Substituted pyrazoloquinazolinones and pyrroloquinazolinones as allosteric modulators of group II metabotropic glutamate receptors
  申请人：DOMAIN THERAPEUTICS

  公开号：US10221179B2

  公开（公告）日：2019-03-05

  The present invention provides pyrazoloquinazolinone and pyrroloquinazolinone derivatives of the general formula (I) and pharmaceutical compositions containing them. Moreover, the compounds of formula (I) and the compositions containing them are provided for use in the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. These pyrazoloquinazolinone and pyrroloquinazolinone derivatives of the general formula (I) can act as modulators of nervous system receptors sensitive to glutamate, in particular as modulators of metabotropic glutamate receptors (mGluRs), which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders.

  本发明提供了通式（I）的吡唑喹唑啉酮和吡咯喹唑啉酮衍生物以及含有它们的药物组合物。此外，本发明还提供了通式（I）的化合物和含有它们的组合物，用于治疗和/或预防与谷氨酸能信号传导和/或功能改变有关的疾病，和/或可受哺乳动物体内谷氨酸水平或信号传导改变影响的疾病。这些通式（I）的吡唑并喹唑啉酮和吡咯并喹唑啉酮衍生物可作为对谷氨酸敏感的神经系统受体的调节剂，特别是作为代谢型谷氨酸受体（mGluRs）的调节剂，这使它们特别适用于治疗和/或预防急性和慢性神经和/或精神疾病。
• Bacterial translation inhibitors, 1-acylindazol-3-ols as anthranilic acid mimics
  作者：Cory Stiff、David R. Graber、Atli Thorarensen、Brian D. Wakefield、Keith R. Marotti、Earline P. Melchior、Michael T. Sweeney、Fusen Han、Douglas C. Rohrer、Gary E. Zurenko、Donna L. Romero

  DOI：10.1016/j.bmcl.2007.08.041

  日期：2008.12

  The discovery and initial optimization of a novel anthranilic acid derived class of antibacterial agents has been described in a recent series of papers. This paper describes the discovery of 1-acylindazol-3-ols as a novel bioisostere of an anthranilic acid. The synthesis and structure-activity relationships of the indazol bioisosteres are described herein. (C) 2008 Published by Elsevier Ltd.