5-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)-3-吡啶磺酰胺 | 1083326-26-4

• 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: 5-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)-3-吡啶磺酰胺
• 中文别名: 5-(4,4,5,5-四甲基-1,3,2-二氧杂环戊硼烷-2-基)吡啶-3-磺酰胺
• 英文名称: pyridine-3-sulfonamide-5-ylboronic acid pinacol ester
• 英文别名: 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinesulfonamide；5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamide
• CAS: 1083326-26-4
• 化学式: C₁₁H₁₇BN₂O₄S
• 分子量: 284.144
• InChiKey: KQVRJGOWCXXVIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.03
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  99.9
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2935009090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  储存温度为2-8°C，并需保存在惰性气体中。

反应信息

• 作为反应物：
  描述：

  5-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)-3-吡啶磺酰胺 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 C₁₄H₁₅N₅O₄S₂
  参考文献：
  名称：

  Discovery of 5-(2-amino-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-N-(tert-butyl)pyridine-3-sulfonamide (CZC24758), as a potent, orally bioavailable and selective inhibitor of PI3K for the treatment of inflammatory disease

  摘要：

  Herein, we disclose the discovery of a series of 7-substituted triazolopyridines which culminated in the identification of 14 (CZC24758), a potent, orally bioavailable small-molecule inhibitor of PI3K gamma, an attractive drug target for inflammatory and autoimmune disorders. Compound 14 has excellent selectivity across the kinome, demonstrates good potency in cell based assays and furthermore exhibits in vivo efficacy in a collagen induced arthritis model in mouse after oral dosing. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.090
• 作为产物：
  描述：

  3-吡啶磺酸 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 五氯化磷 、 potassium acetate 、 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.75h， 生成 5-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)-3-吡啶磺酰胺
  参考文献：
  名称：

  [EN] QUINAZOLINES AS POTASSIUM ION CHANNEL INHIBITORS
  [FR] QUINAZOLINES COMME INHIBITEURS DES CANAUX IONIQUES POTASSIQUES

  摘要：

  其中A、X、Y、Z、R1和R24如所述的(I)式化合物。这些化合物作为钾通道功能的抑制剂以及用于治疗和预防心律不齐、IKur相关疾病和其他由离子通道功能介导的疾病是有用的。

  公开号：

  WO2011028741A1

文献信息

• Quinazolines as potassium ion channel inhibitors
  申请人：Johnson James A.

  公开号：US08575184B2

  公开（公告）日：2013-11-05

  A compound of formula (I) wherein A, X, Y, Z, R1 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

  化合物的化学式为(I)，其中A、X、Y、Z、R1和R24的描述见本文。这些化合物可用作钾通道功能的抑制剂，用于治疗和预防心律失常、IKur相关疾病和其他离子通道功能介导的疾病。
• NAPHTHYRIDINE, DERIVATIVES AS P13 KINASE INHIBITORS
  申请人：Adams Nicholas D.

  公开号：US20100179143A1

  公开（公告）日：2010-07-15

  Invented is a method of inhibiting the activity/function of PI3 kinases using naphthyridine derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of naphthyridine derivatives.

  本发明涉及使用萘啶衍生物抑制PI3激酶的活性/功能的方法。本发明还涉及通过给予萘啶衍生物治疗自身免疫性疾病、炎症性疾病、心血管疾病、神经退行性疾病、过敏、哮喘、胰腺炎、多器官衰竭、肾脏疾病、血小板聚集、癌症、精子运动能力、移植排斥、移植物排斥和肺部损伤等一种或多种疾病状态的方法。
• Selective <i>I</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
  作者：Prashantha Gunaga、John Lloyd、Somanadham Mummadi、Abhisek Banerjee、Naveen Kumar Dhondi、James Hennan、Veena Subray、Ramya Jayaram、Nagendra Rajugowda、Kommuri Umamaheshwar Reddy、Duraimurugan Kumaraguru、Umasankar Mandal、Dasthagiri Beldona、Ashok Kumar Adisechen、Navnath Yadav、Jayakumar Warrier、James A. Johnson、Harinath Sale、Siva Prasad Putlur、Ajay Saxena、Anjaneya Chimalakonda、Sandhya Mandlekar、MaryLee Conder、Dezhi Xing、Arun Kumar Gupta、Anuradha Gupta、Richard Rampulla、Arvind Mathur、Paul Levesque、Ruth R. Wexler、Heather J. Finlay

  DOI：10.1021/acs.jmedchem.6b01889

  日期：2017.5.11

  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.
• WO2008/150827
  申请人：——

  公开号：——

  公开（公告）日：——
• Identification, Characterization, and Optimization of 2,8-Disubstituted-1,5-naphthyridines as Novel <i>Plasmodium falciparum</i> Phosphatidylinositol-4-kinase Inhibitors with in Vivo Efficacy in a Humanized Mouse Model of Malaria
  作者：Nishanth Kandepedu、Diego Gonzàlez Cabrera、Srinivas Eedubilli、Dale Taylor、Christel Brunschwig、Liezl Gibhard、Mathew Njoroge、Nina Lawrence、Tanya Paquet、Charles J. Eyermann、Thomas Spangenberg、Gregory S. Basarab、Leslie J. Street、Kelly Chibale

  DOI：10.1021/acs.jmedchem.8b00648

  日期：2018.7.12

  A novel 2,8-disubstituted-1,5-naphthyridine hit compound stemming from the open access Medicines for Malaria Venture Pathogen Box formed a basis for a hit-to-lead medicinal chemistry program. Structure-activity relationship investigations resulted in compounds with potent antiplasmodial activity against both chloroquine sensitive (NF54) and multidrug resistant (K1) strains of the human malaria parasite Plasmodium falciparum. In the humanized P. falciparum mouse efficacy model, one of the frontrunner compounds showed in vivo efficacy at an oral dose of 4 X 50 mg.g(-1). In vitro mode-of-action studies revealed Plasmodium falciparum phosphatidylinositol-4-kinase as the target.