(R)-tert-butyl 4-(4-(4-(dimethylamino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonamido)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate | 1274804-57-7

• 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: (R)-tert-butyl 4-(4-(4-(dimethylamino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonamido)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate
• 英文别名: tert-butyl 4-[[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylamino]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidine-7-carboxylate
• CAS: 1274804-57-7
• 化学式: C₃₁H₃₉F₃N₆O₆S₃
• 分子量: 744.88
• InChiKey: KGMXPKLXBDQNMD-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  49
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  193
• 氢给体数：
  2
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl 4-(4-(4-(dimethylamino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonamido)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以81%的产率得到4-((R)-3-dimethylamino-1-phenylsulfanylmethyl-propylamino)-N-(5,6,7,8-tetrahydro-pyrido[3,4-d]pyrimidin-4-yl)-3-(trifluoromethanesulfonyl)benzenesulfonamide
  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：

  4-羟基-5,8-二氢-6H-吡啶并[3,4-d]嘧啶-7-羧酸叔丁酯 在 四氯化碳 、 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 三苯基膦 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 1,4-二氧六环 、 1,2-二氯乙烷 为溶剂， 反应 3.0h， 生成 (R)-tert-butyl 4-(4-(4-(dimethylamino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonamido)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-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

文献信息

• 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 TREATMENT OF CANCER
  申请人：Novartis AG

  公开号：EP2475661B1

  公开（公告）日：2013-10-23
• US8809352B2
  申请人：——

  公开号：US8809352B2

  公开（公告）日：2014-08-19