3-溴吡啶-4-磺酰氯 | 886371-33-1

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 3-溴吡啶-4-磺酰氯
• 中文别名: 3-溴-吡啶-4-磺酰氯
• 英文名称: 3-bromopyridine-4-sulfonyl chloride
• CAS: 886371-33-1
• 化学式: C₅H₃BrClNO₂S
• 分子量: 256.507
• InChiKey: ROJXVEVYKKTMKL-UHFFFAOYSA-N

物化性质

• 沸点：
  328.0±27.0 °C(Predicted)
• 密度：
  1.893±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-溴吡啶-4-磺酰氯 在 四(三苯基膦)钯 、 氨 、 六甲基二锡 、 lithium chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 36.0h， 生成 3-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridine-4-sulfonamide
  参考文献：
  名称：

  Selective I_Kur Inhibitors for the Potential Treatment of Atrial Fibrillation: Optimization of the Phenyl Quinazoline Series Leading to Clinical Candidate 5-[5-Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide

  摘要：

  We have recently disclosed 5-phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine 1 as a potent I-Kur current blocker with selectivity versus hERG, Na and Ca channels, and an acceptable preclinical PK profile. Upon further characterization in vivo, compound 1 demonstrated an unacceptable level of brain penetration. In an effort to reduce the level of brain penetration while maintaining the overall profile, SAR was developed at the C2' position for a series of close analogues by employing hydrogen bond donors. As a result, 5-[5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide (25) was identified as the lead compound in this series. Compound 25 showed robust effects in rabbit and canine pharmacodynamic models and an acceptable cross-species pharmacokinetic profile and was advanced as the clinical candidate. Further optimization of 25 to mitigate pH-dependent absorption resulted in identification of the corresponding phosphoramide prodrug (29) with an improved solubility and pharmacokinetic profile.

  DOI：

  10.1021/acs.jmedchem.6b01889
• 作为产物：
  描述：

  3,4-二溴吡啶 在 potassium tert-butylate 、 水 、 氯 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 3-溴吡啶-4-磺酰氯
  参考文献：
  名称：

  一种嘧啶-2,4-二胺衍生物及其制备方法和用途

  摘要：

  本发明提供一种嘧啶‑2,4‑二胺衍生物及其制备方法和用途，具体地，所述的嘧啶‑2,4‑二胺衍生物如式一所示。本发明提供的嘧啶‑2,4‑二胺衍生物对耐药的肿瘤细胞株具有很高的抑制活性，尤其对EGFR小分子抑制剂耐药的肿瘤细胞株，进一步地，本发明提供的嘧啶‑2,4‑二胺衍生物可以用于治疗晚期肿瘤，尤其是晚期肺癌，特别是小细胞肺癌和靶向药治疗抵抗的非小细胞肺癌。

  公开号：

  CN116444488A

文献信息

• N-SULFONYL THIAZOLYLPIPERAZINE DERIVATIVES AND RELATED N-SULFONYL HETEROCYCLIC DERIVATIVES FOR THE TREATMENT OF NEURO DEGENERATIVE DISEASES
  申请人：GRIFFIOEN Gerard

  公开号：US20100197703A1

  公开（公告）日：2010-08-05

  This invention provides thiazolylpiperazine derivatives, and N-sulfonyl heterocyclic derivatives including phenyl- and benzyl-thiazolylpiperidine derivatives, and pharmaceutically acceptable salts thereof, which are useful active ingredients for administration in a method for the treatment of an α-synucleopathy such as Parkinson's disease, diffuse Lewy body disease, traumatic brain injury, amyotrophic lateral sclerosis, Niemann-Pick disease, Hallervorden-Spatz syndrome, Down syndrome, neuroaxonal dystrophy, multiple system atrophy and Alzheimer's disease. This invention also provides methods for making such derivatives, and pharmaceutical compositions including such derivatives together with pharmaceutically acceptable excipients.

  该发明提供了噻唑基哌嗪衍生物，以及包括苯基和苄基噻唑基哌啶衍生物的N-磺酰杂环衍生物，以及其药学上可接受的盐，这些是用于治疗α-突触核蛋白病的有效活性成分，如帕金森病、弥漫性小体病、创伤性脑损伤、肌萎缩侧索硬化症、尼曼-匹克病、哈勒沃登-施帕茨综合征、唐氏综合征、神经轴突萎缩、多系统萎缩和阿尔茨海默病的治疗方法。该发明还提供了制备这些衍生物的方法，以及包括这些衍生物和药学上可接受的辅料的药物组合物。
• 一种嘧啶-2,4-二胺衍生物及其制备方法和用途
  申请人：上海立森印迹医药技术有限公司

  公开号：CN116444488A

  公开（公告）日：2023-07-18

  本发明提供一种嘧啶‑2,4‑二胺衍生物及其制备方法和用途，具体地，所述的嘧啶‑2,4‑二胺衍生物如式一所示。本发明提供的嘧啶‑2,4‑二胺衍生物对耐药的肿瘤细胞株具有很高的抑制活性，尤其对EGFR小分子抑制剂耐药的肿瘤细胞株，进一步地，本发明提供的嘧啶‑2,4‑二胺衍生物可以用于治疗晚期肿瘤，尤其是晚期肺癌，特别是小细胞肺癌和靶向药治疗抵抗的非小细胞肺癌。
• Design and Discovery of a Selective Small Molecule κ Opioid Antagonist (2-Methyl-<i>N</i>-((2′-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242)
  作者：Patrick R. Verhoest、Aarti Sawant Basak、Vinod Parikh、Matthew Hayward、Gregory W. Kauffman、Vanessa Paradis、Stanton F. McHardy、Stafford McLean、Sarah Grimwood、Anne W. Schmidt、Michelle Vanase-Frawley、Jodi Freeman、Jeffrey Van Deusen、Loretta Cox、Diane Wong、Spiros Liras

  DOI：10.1021/jm2006035

  日期：2011.8.25

  By use of parallel chemistry coupled with physicochemical property design, a series of selective kappa opioid antagonists have been discovered. The parallel chemistry strategy utilized key monomer building blocks to rapidly expand the desired SAR space. The potency and selectivity of the in vitro kappa antagonism were confirmed in the tail-flick analgesia model. This model was used to build an exposure-response relationship between the kappa K-i and the free brain drug levels. This strategy identified 2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242, which entered phase 1 clinical testing and has demonstrated target engagement in healthy volunteers.
• PHENYL- AND BENZYLTHIAZOLYLPIPERAZINE DERIVATIVES FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：reMYND NV

  公开号：EP2188272B1

  公开（公告）日：2016-02-24
• THIADIAZOLE DERIVATIVES FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：GRIFFIOEN Gerard

  公开号：US20090054410A1

  公开（公告）日：2009-02-26

  This invention provides specifically substituted 1,2,4-thiadiazole derivatives for use in the treatment of an α-synucleopathy such as Parkinson's disease, diffuse Lewy body disease, traumatic brain injury, amyotrophic lateral sclerosis, Niemann-Pick disease, Hallervorden-Spatz syndrome, Down syndrome, neuroaxonal dystrophy, multiple system atrophy and Alzheimer's disease. This invention also provides various methods for producing such substituted 1,2,4-thiadiazole derivatives.