4,5,7,8-tetrahydro-1,2,3a,6-tetraaza-azulene-6-carboxylic acid tert-butyl ester | 1274804-51-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并二氮卓类
• 英文名称: 4,5,7,8-tetrahydro-1,2,3a,6-tetraaza-azulene-6-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 8,9-dihydro-5H-[1,2,4]triazolo[4,3-D][1,4]diazepine-7(6H)-carboxylate；tert-butyl 5,6,8,9-tetrahydro-[1,2,4]triazolo[4,3-d][1,4]diazepine-7-carboxylate
• CAS: 1274804-51-1
• 化学式: C₁₁H₁₈N₄O₂
• 分子量: 238.29
• InChiKey: KZIKIXQLGMNAHH-UHFFFAOYSA-N

物化性质

• 沸点：
  392.2±52.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  60.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,5,7,8-tetrahydro-1,2,3a,6-tetraaza-azulene-6-carboxylic acid tert-butyl ester 在 copper(l) iodide 、 溴 、 (1S,2S)-(+)-N,N'-二甲基环己烷-1,2-二胺 、 caesium carbonate 、 sodium hydroxide 作用下， 以 水 、 甲苯 为溶剂， 反应 32.0h， 生成 (R)-tert-butyl 3-(4-((4-(dimethylamino)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenylsulfonamido)-8,9-dihydro-5H-[1,2,4]triazolo[4,3-d][1,4]diazepine-7(6H)-carboxylate
  参考文献：
  名称：

  The Role of the Acidity of N-Heteroaryl Sulfonamides as Inhibitors of Bcl-2 Family Protein–Protein Interactions

  摘要：

  Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263.

  DOI：

  10.1021/ml300321d
• 作为产物：
  描述：

  肼羧酸 、 1-Boc-1,4-二氮杂-5-环庚酮 在 trimethoxonium tetrafluoroborate 作用下， 以 二氯甲烷 为溶剂， 反应 32.0h， 以61%的产率得到4,5,7,8-tetrahydro-1,2,3a,6-tetraaza-azulene-6-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  The Role of the Acidity of N-Heteroaryl Sulfonamides as Inhibitors of Bcl-2 Family Protein–Protein Interactions

  摘要：

  Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263.

  DOI：

  10.1021/ml300321d

文献信息

• [EN] SULFONAMIDES AS INHIBITORS OF BCL-2 FAMILY PROTEINS FOR THE TREATMENT OF CANCER<br/>[FR] SULFAMIDES UTILISÉS COMME INHIBITEURS DES PROTÉINES DE LA FAMILLE DE BCL-2 DANS LE TRAITEMENT DU CANCER
  申请人：NOVARTIS AG

  公开号：WO2011029842A1

  公开（公告）日：2011-03-17

  The present invention includes novel compound and methods of treating a disease or disorder by antagonizing Bcl-2 family proteins, particularly compounds of Formula (I) or pharmaceutically acceptable salt thereof, as well as methods of treating a disease, disorder, or syndrome associated with Bcl-2 inhibition, particularly hyperproliferative diseases. The present invention also includes pharmaceutical compositions including compounds of formula (I) and pharmaceutically acceptable salts thereof.

  本发明涉及一种新型化合物和通过拮抗Bcl-2家族蛋白治疗疾病或紊乱的方法，特别是公式(I)的化合物或其药用盐，以及治疗与Bcl-2抑制相关的疾病、紊乱或综合征的方法，特别是高增殖性疾病。本发明还包括包括公式(I)的化合物和其药用盐的药物组合物。
• SULFONAMIDE COMPOUNDS
  申请人：Miller-Moslin Karen

  公开号：US20120165298A1

  公开（公告）日：2012-06-28

  The present invention includes novel compound and methods of treating a disease or disorder by antagonizing Bcl-2 family proteins, particularly compounds of formula (I): or pharmaceutically acceptable salt thereof, as well as methods of treating a disease, disorder, or syndrome associated with Bcl-2 inhibition, particularly hyperproliferative diseases. The present invention also includes pharmaceutical compositions including compounds of formula I and pharmaceutically acceptable salts thereof.

  本发明涉及一种新型化合物和通过拮抗Bcl-2家族蛋白治疗疾病或障碍的方法，特别是公式(I)的化合物或其药学上可接受的盐，以及治疗与Bcl-2抑制相关的疾病、障碍或综合症的方法，特别是过度增殖性疾病。本发明还包括包含公式I的化合物和其药学上可接受的盐的制药组合物。
• Sulfonamides as inhibitors of Bcl-2 family proteins for the treatments of cancer
  申请人：Miller-Moslin Karen

  公开号：US08809352B2

  公开（公告）日：2014-08-19

  The present invention includes novel compound and methods of treating a disease or disorder by antagonizing Bcl-2 family proteins, particularly compounds of formula (I): or pharmaceutically acceptable salt thereof, as well as methods of treating a disease, disorder, or syndrome associated with Bcl-2 inhibition, particularly hyperproliferative diseases. The present invention also includes pharmaceutical compositions including compounds of formula I and pharmaceutically acceptable salts thereof.

  本发明涉及新型化合物及其通过拮抗Bcl-2家族蛋白治疗疾病或疾病的方法，特别是公式(I)的化合物或其药学上可接受的盐，以及治疗与Bcl-2抑制相关的疾病、疾病或综合征的方法，特别是增殖过度性疾病。本发明还包括包括公式I的化合物及其药学上可接受的盐的制药组合物。
• SULFONAMIDES AS INHIBITORS OF BCL-2 FAMILY PROTEINS FOR THE TREATMENT OF CANCER
  申请人：Novartis AG

  公开号：EP2475661A1

  公开（公告）日：2012-07-18
• US8809352B2
  申请人：——

  公开号：US8809352B2

  公开（公告）日：2014-08-19