4-溴-2-氯-5-硝基吡啶 | 1261767-18-3

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 中文名称: 4-溴-2-氯-5-硝基吡啶
• 英文名称: 4-bromo-2-chloro-5-nitropyridine
• CAS: 1261767-18-3
• 化学式: C₅H₂BrClN₂O₂
• mdl: MFCD17014986
• 分子量: 237.44
• InChiKey: DVBAUHSXNQFCQQ-UHFFFAOYSA-N

物化性质

• 沸点：
  273.4±35.0 °C(Predicted)
• 密度：
  1.936±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  58.7
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 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：

  4-溴-2-氯-5-硝基吡啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 生成 1-methyl-4-(5-nitro-4-phenylpyridin-2-yl)piperazine
  参考文献：
  名称：

  发现新型 TrkA 变构抑制剂：基于结构的虚拟筛选、生物学评估和初步 SAR 研究

  摘要：

  原肌球蛋白受体激酶 A (TrkA) 是治疗多种肿瘤类型和慢性疼痛的潜在治疗靶点。然而，大多数报道的 TrkA 抑制剂是缺乏亚型选择性的 ATP 竞争性泛 Trks 抑制剂。选择性 TrkA 抑制剂可提供有价值的治疗益处。在这里，我们描述了通过基于结构的虚拟筛选发现新型 TrkA 变构抑制剂。选择了一个有希望的命中（D5261， TrkA 细胞 IC 50  = 3.32 μM）进行进一步研究。计算了 TrkA 和D5261之间的结合自由能。此外，对D5261的初步构效关系 (SAR) 研究进行了调查。结果表明D5261可作为开发 TrkA 变构抑制剂的起点。

  DOI：

  10.1016/j.ejmech.2021.114022

文献信息

• [EN] HETEROCYCLIC CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES HÉTÉROCYCLIQUES DES RÉCEPTEURS CGRP
  申请人：MERCK SHARP & DOHME

  公开号：WO2016022644A1

  公开（公告）日：2016-02-11

  The present invention is directed to heterocyclic compounds which are antagonists of CGRP receptors and may be useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及杂环化合物，其为CGRP受体拮抗剂，可能在治疗或预防涉及CGRP的疾病（如偏头痛）方面有用。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的疾病中使用这些化合物和组合物。
• 1,4-DIHYDROBENZO[D]PYRAZOLO[3,4-F][1,3]DIAZEPINE DERIVATIVES AND RELATED COMPOUNDS AS LRRK2, NUAK1 AND/OR TYK2 KINASE MODULATORS FOR THE TREATMENT OF E.G. AUTOIMMUNE DISEASE
  申请人：Origenis GmbH

  公开号：EP4028017A1

  公开（公告）日：2022-07-20
• [EN] 1,4-DIHYDROBENZO[D]PYRAZOLO[3,4-F][1,3]DIAZEPINE DERIVATIVES AND RELATED COMPOUNDS AS LRRK2, NUAK1 AND/OR TYK2 KINASE MODULATORS FOR THE TREATMENT OF E.G. AUTOIMMUNE DISEASE<br/>[FR] DÉRIVÉS DE 1,4-DIHYDROBENZO[D]PYRAZOLO[3,4-F][1,3]DIAZÉPINE ET COMPOSÉS APPARENTÉS UTILISÉS EN TANT QUE MODULATEURS DE KINASES LRRK2, NUAK1 ET/OU TYK2 POUR LE TRAITEMENT, PAR EXEMPLE DE MALADIES AUTO-IMMUNES
  申请人：ORIGENIS GMBH

  公开号：WO2021048618A1

  公开（公告）日：2021-03-18

  The present invention relates to compounds of formula (I) that are capable of modulating, e.g., inhibiting or activating, one or more kinases, especially LRRK2 and/or NUAK1 and/or TYK2 or mutants thereof. The compounds are useful for treating diseases, such as 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. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 40 to 146; examples 1 to 63; compounds 1 to 248; tables 1 to 3). Preferred compounds are e.g. 1,4-dihydrobenzo[d]pyrazolo[3,4-f] [1,3]diazepine derivatives and related compounds. An exemplary compound is e.g. 5-(2,6-difluorophenyl)-8-methoxy-1,4- dihydrobenzo[d]pyrazolo[3,4-f][1,3]diazepine (example 49). (Formula (II):
• [EN] 1,4-DIHYDROBENZO[D]PYRAZOLO[3,4-F][1,3]DIAZEPINE DERIVATIVES AND RELATED COMPOUNDS AS LRRK2, NUAK1 AND/OR TYK2 KINASE MODULATORS FOR THE TREATMENT OF E.G. AUTOIMMUNE DISEASE<br/>[FR] DÉRIVÉS DE 1,4-DIHYDROBENZO[D]PYRAZOLO[3,4-F][1,3]DIAZÉPINE ET COMPOSÉS APPARENTÉS UTILISÉS EN TANT QUE MODULATEURS DE KINASES LRRK2, NUAK1 ET/OU TYK2 POUR LE TRAITEMENT PAR EXEMPLE DE MALADIES AUTO-IMMUNES
  申请人：ORIGENIS GMBH

  公开号：WO2021048620A1

  公开（公告）日：2021-03-18

  The present invention relates to compounds of formula (I) that are capable of modulating, e.g., inhibiting or activating, one or more kinases, especially LRRK2 and/or NUAK1 and/or TYK2 or mutants thereof. The compounds are useful for treating diseases, such as 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. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 40 to 146; examples 1 to 63; compounds 1 to 248; tables 1 to 3). Preferred compounds are e.g. 1,4-dihydrobenzo[d]pyrazolo[3,4-f] [1,3]diazepine derivatives and related compounds. An exemplary compound is e.g. 5-(2,6-difluorophenyl)-8-methoxy-1,4- dihydrobenzo[d]pyrazolo[3,4-f][1,3]diazepine (example 49). (Formula (II)).
• Discovery of novel TrkA allosteric inhibitors: Structure-based virtual screening, biological evaluation and preliminary SAR studies
  作者：Jing Guo、Shuang Xiang、Jie Wang、Yang Zhou、Zuqin Wang、Zhang Zhang、Ke Ding、Xiaoyun Lu

  DOI：10.1016/j.ejmech.2021.114022

  日期：2022.1

  numerous tumor types and chronic pain. However, most of the reported TrkA inhibitors are ATP competitive pan-Trks inhibitors that lack subtype selectivity. A selective TrkA inhibitor may provide valuable therapeutic benefits. Here, we described the discovery of novel TrkA allosteric inhibitors by structure-based virtual screening. A promising hit (D5261, TrkA cell IC50 = 3.32 μM) was selected for further

  原肌球蛋白受体激酶 A (TrkA) 是治疗多种肿瘤类型和慢性疼痛的潜在治疗靶点。然而，大多数报道的 TrkA 抑制剂是缺乏亚型选择性的 ATP 竞争性泛 Trks 抑制剂。选择性 TrkA 抑制剂可提供有价值的治疗益处。在这里，我们描述了通过基于结构的虚拟筛选发现新型 TrkA 变构抑制剂。选择了一个有希望的命中（D5261， TrkA 细胞 IC 50  = 3.32 μM）进行进一步研究。计算了 TrkA 和D5261之间的结合自由能。此外，对D5261的初步构效关系 (SAR) 研究进行了调查。结果表明D5261可作为开发 TrkA 变构抑制剂的起点。