2-chloro-5-hydrazinobenzoic acid hydrochloride | 184163-49-3

• 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: 2-chloro-5-hydrazinobenzoic acid hydrochloride
• 英文别名: 2-chloro-5-hydrazinylbenzoic acid;hydrochloride
• CAS: 184163-49-3
• 化学式: C₇H₇ClN₂O₂*ClH
• mdl: MFCD08087438
• 分子量: 223.059
• InChiKey: LYSZNCNDYFXUJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.16
• 重原子数：
  13
• 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：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-5-hydrazinobenzoic acid hydrochloride 在 sodium acetate 、 溶剂黄146 、 三乙胺 作用下， 反应 3.0h， 生成 (E)-5-(4-((5-(4-azidophenyl)furan-2-yl)methylene)-5-oxo-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-chlorobenzoic acid
  参考文献：
  名称：

  Inhibition of the FAD containing ER oxidoreductin 1 (Ero1) protein by EN-460 as a strategy for treatment of multiple myeloma

  摘要：

  Multiple myeloma (MM) cells demonstrate high basal endoplasmic reticulum (ER) stress and are typically exquisitely sensitive to agents such as proteasome inhibitors that activate the unfolded protein response. The flavin adenosine dinucleotide (FAD) containing endoplasmic reticulum oxidoreductin enzyme (Ero1L) catalyzes de-novo disulfide bridge formation of ER resident proteins and contributes to proper protein folding. Here we show that increased Ero1L expression is prognostic of poor outcomes for MM patients relapsing on therapy. We propose that targeting protein folding via inhibition of Ero1L may represent a novel therapeutic strategy for the treatment of MM. In this report we show that treatment of MM cells with EN-460, a known inhibitor of ERO1L, was sufficient to inhibit cell proliferation and induce apoptosis. Furthermore, we show that cell death correlated in part with induction of ER stress. We also show that EN460 inhibited the enzyme activity of Ero1L, with an IC50 of 22.13 mu M, consistent with previous reports. However, EN-460 was also found to inhibit other FAD-containing enzymes including MAO-A (IC50 = 7.91 mu M), MAO-B (IC50 = 30.59 mu M) and LSD1 (IC50 = 4.16 mu M), suggesting overlap in inhibitor activity and the potential need to develop more specific inhibitors to enable pharmacological validation of ERO1L as a target for the treatment of MM. We additionally prepared and characterized azide-tagged derivatives of EN-460 as possible functional probe compounds (e.g., for photo-affinity labeling) for future target-engagement studies and further development of structure-activity relationships.

  DOI：

  10.1016/j.bmc.2019.02.016
• 作为产物：
  描述：

  3-carboxy-4-chlorobenzene-1-diazonium chloride 在 盐酸 、 tin(ll) chloride 作用下， 以 水 为溶剂， 反应 1.0h， 以71%的产率得到2-chloro-5-hydrazinobenzoic acid hydrochloride
  参考文献：
  名称：

  Dihydrodipyrazolopyridinylbenzamide and -sulfonamide inhibitors of B7-1

  摘要：

  本发明提供了一种化合物I的公式以及其用于免疫治疗移植排斥或自身免疫疾病的用途。

  公开号：

  US20040024008A1

文献信息

• Synthesis and Structure–Affinity Relationship of Small Molecules for Imaging Human CD80 by Positron Emission Tomography
  作者：Marco F. Taddio、Linjing Mu、Claudia A. Castro Jaramillo、Tanja Bollmann、Dominik M. Schmid、Lukas P. Muskalla、Tim Gruene、Aristeidis Chiotellis、Simon M. Ametamey、Roger Schibli、Stefanie D. Krämer

  DOI：10.1021/acs.jmedchem.9b00858

  日期：2019.9.12

  tracer for imaging CD80 by positron emission tomography (PET). Novel CD80 ligands were synthesized and tested by SPR for affinity to human CD80 (hCD80) and displacement of endogenous ligands. Several compounds bound with one-digit nanomolar affinity to hCD80 and displaced CTLA-4 and CD28 at nanomolar concentrations. A structure-affinity relationship study revealed relevant moieties for strong affinity to

  共刺激分子CD80是免疫激活的早期标记。它在活化的抗原呈递细胞上调。我们旨在开发一种通过正电子发射断层扫描（PET）对CD80成像的示踪剂。合成了新型CD80配体，并通过SPR测试了对人CD80（hCD80）的亲和力和内源性配体的置换。几种化合物以1纳摩尔的亲和力与hCD80结合，并以纳摩尔浓度取代了CTLA-4和CD28。结构亲和关系研究揭示了与hCD80的强亲和力相关的部分，以及进一步修饰的位置。铅化合物MT107（7f）被碳11放射性标记。在体外，[11C] MT107显示出与hCD80阳性组织的特异性结合和高血浆蛋白结合。在体内，[11C] MT107积累在肝脏，胆囊，和肠道，但很少出现在hCD80阳性异种移植物中。高血浆蛋白结合和广泛的胆汁排泄可能导致不利的体内性能。
• Substituted 1-phenyl-3-pyrazolecarboxamides active on neurotensin
  申请人：Sanofi

  公开号：US05723483A1

  公开（公告）日：1998-03-03

  The invention relates to new substituted 1-phenyl-3-pyrazolecarboxamides having a great affinity for human neurotensin receptors, to a process for preparing them and to pharmaceutical compositions containing them as active principles. More particularly, this invention relates to the discovery that the affinity for neurotensin receptors, especially human neurotensin receptors, is increased by substituting the phenyl group of 1-phenyl-3-pyrazolecarboxamide compounds with particular groups.

  本发明涉及新的取代的1-苯基-3-吡唑甲酰胺类化合物，其具有极强的与人类神经针对素受体的亲和力，以及制备它们的方法和含有它们作为活性成分的制药组合物。更具体地说，本发明是发现通过用特定基团取代1-苯基-3-吡唑甲酰胺化合物的苯基，可以增加其与神经针对素受体，特别是人类神经针对素受体的亲和力。
• Hydrazine derivative compounds as intermediates for preparing
  申请人：Sanofi

  公开号：US05936123A1

  公开（公告）日：1999-08-10

  This invention relates to intermediate compounds which are useful for making substituted 1-phenyl-3-pyrazolecarboxamides. The compounds of the invention have the formula: ##STR1## in which: R'.sub.2 and R'.sub.3 each independently represent a hydrogen, a (C.sub.1 -C.sub.6)alkyl, a (C.sub.3 -C.sub.8)cycloalkyl, a (C.sub.3 -C.sub.8)cycloalkylmethyl; or R'.sub.2 and R'.sub.3 together constitute a trimethylene, tetramethylene or pentamethylene group; R.sub.y is at position 4 or at position 5 and represents a group chosen from: cyano, carboxyl, (C.sub.1 -C.sub.4)alkoxycarbonyl, benzyloxycarbonyl, sulpho, (C.sub.1 -C.sub.4)alkylsulphonylamino, (C.sub.1 -C.sub.4)alkylphenylsulphonylamino, carbamoyl, (C.sub.1 -C.sub.4)alkylcarboxamido; on condition that R'.sub.2 and R'.sub.3 do not simultaneously represent hydrogen and on condition that R'.sub.2 is other than methyl when R.sub.y is a sulpho group. The salts of the above compounds are also part of the invention.

  本发明涉及中间化合物，其用于制备取代的1-苯基-3-吡唑羧酰胺。本发明中的化合物具有以下结构式：##STR1## 其中：R'.sub.2和R'.sub.3各自独立地表示氢、(C.sub.1-C.sub.6)烷基、(C.sub.3-C.sub.8)环烷基、(C.sub.3-C.sub.8)环烷基甲基；或R'.sub.2和R'.sub.3共同构成三亚甲基、四亚甲基或五亚甲基基团；R.sub.y位于4位或5位，并表示从以下组中选择的一组：氰基、羧基、(C.sub.1-C.sub.4)烷氧羰基、苄氧羰基、磺酰基、(C.sub.1-C.sub.4)烷基磺酰氨基、(C.sub.1-C.sub.4)烷基苯基磺酰氨基、氨基甲酰基、(C.sub.1-C.sub.4)烷基羧酰胺；条件是R'.sub.2和R'.sub.3不能同时表示氢，并且当R.sub.y为磺酰基时，R'.sub.2不得为甲基。上述化合物的盐也是本发明的一部分。
• Structure–activity studies of a series of dipyrazolo[3,4- b :3′,4′- d ]pyridin-3-ones binding to the immune regulatory protein B7.1
  作者：Neal J. Green、Jason Xiang、Jing Chen、Lihren Chen、Audrey M. Davies、Dave Erbe、Steve Tam、James F. Tobin

  DOI：10.1016/s0968-0896(03)00183-4

  日期：2003.7

  The interaction of co-stimulatory molecules on T cells with 137 molecules on antigen presenting cells plays an important role in the activation of naive T cells. Consequently, agents that disrupt these interactions should have applications in treatment of transplant rejection as well as autoimmune diseases. To this end, specific small molecule inhibitors of human B7.1 were identified and characterized. Herein, we report the identification of potent small molecule inhibitors of the B7.1-CD28 interaction. In a high-throughput screen we identified several leads that prevented the interaction of B7.1 with CD28 with activities in the nanomolar to low micromolar range. One of these, the dihydrodipyrazolopyridinone 1, was subsequently shown to bind the V-like domain of human B7.1 at equimolar stoichiometry. With this as a starting point, we report here the synthesis and initial in vitro structure-activity relationships of a series of these compounds. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Discovery of Lead Compounds Targeting the Bacterial Sliding Clamp Using a Fragment-Based Approach
  作者：Zhou Yin、Louise R. Whittell、Yao Wang、Slobodan Jergic、Michael Liu、Elizabeth J. Harry、Nicholas E. Dixon、Jennifer L. Beck、Michael J. Kelso、Aaron J. Oakley

  DOI：10.1021/jm500122r

  日期：2014.3.27

  The bacterial sliding clamp (SC), also known as the DNA polymerase III β subunit, is an emerging antibacterial target that plays a central role in DNA replication, serving as a protein-protein interaction hub with a common binding pocket to recognize linear motifs in the partner proteins. Here, fragment-based screening using X-ray crystallography produced four hits bound in the linear-motif-binding pocket of the Escherichia coli SC. Compounds structurally related to the hits were identified that inhibited the E. coli SC and SC-mediated DNA replication in vitro. A tetrahydrocarbazole derivative emerged as a promising lead whose methyl and ethyl ester prodrug forms showed minimum inhibitory concentrations in the range of 21-43 μg/mL against representative Gram-negative and Gram-positive bacteria species. The work demonstrates the utility of a fragment-based approach for identifying bacterial sliding clamp inhibitors as lead compounds with broad-spectrum antibacterial activity.