7-bromo-1-(trans-4-hydroxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one | 1441765-73-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 7-bromo-1-(trans-4-hydroxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one
• CAS: 1441765-73-6
• 化学式: C₁₂H₁₅BrN₄O₂
• 分子量: 327.181
• InChiKey: KIUMQGSWVKYGSO-ZKCHVHJHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  78.35
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  7-bromo-1-(trans-4-hydroxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 四(三苯基膦)钯 、 三(邻甲基苯基)磷 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 生成 1-((1r,4r)-4-hydroxycyclohexyl)-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyra1r,4rzin-2(1H)-one
  参考文献：
  名称：

  Optimization of a Series of Triazole Containing Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors and the Discovery of CC-115

  摘要：

  We report here the synthesis and structure activity relationship (SAR) of a novel series of triazole containing mammalian target of rapamycin (mTOR) kinase inhibitors. SAR studies examining the potency, selectivity, and PK parameters for a series of triazole containing 4,6- or 1,7-disubstituted-3,4-dihydropyrazino[2,3-b]pyrazine-2(1H)-ones resulted in the identification of triazole containing mTOR kinase inhibitors with improved PK properties. Potent compounds from this series were found to block both mTORC1(p56) and mTORC2(pAktS473) signaling in PC-3 cancer cells, in vitro and in vivo. When assessed in efficacy models, analogs exhibited dose-dependent efficacy in tumor xenograft models. This work resulted in the selection of CC-115 for clinical development.

  DOI：

  10.1021/acs.jmedchem.5b00627
• 作为产物：
  描述：

  ethyl 2-(6-chloropyrazin-2-ylamino)acetate 在 N-溴代丁二酰亚胺(NBS) 、 palladium(II) hydroxide 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 、 二甲基亚砜 为溶剂， 反应 124.5h， 生成 7-bromo-1-(trans-4-hydroxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one
  参考文献：
  名称：

  Discovery of Mammalian Target of Rapamycin (mTOR) Kinase Inhibitor CC-223

  摘要：

  We report here the synthesis and structure-activity relationship (SAR) of a novel series of mammalian target of rapamycin (mTOR) kinase inhibitors. A series of 4,6- or 1,7-disubstituted-3,4-dihydropyrazino[2,3-b]pyrazine-2(1H)-ones were optimized for in vivo efficacy. These efforts resulted in the identification of compounds with excellent mTOR kinase inhibitory potency, with exquisite kinase selectivity over the related lipid kinase PI3K. The improved PK properties of this series allowed for exploration of in vivo efficacy and ultimately the selection of CC-223 for clinical development.

  DOI：

  10.1021/acs.jmedchem.5b00626

文献信息

• PHARMACEUTICAL COMPOSITIONS OF 7-(6-(2-HYDROXYPROPAN-2-YL)PYRIDIN-3-YL)-1-((TRANS)-4-METHOXYCYCLOHEXYL)-3,4-DIHYDROPYRAZINO [2,3-B]PYRAZIN-2(1H)-ONE, A SOLID FORM THEREOF AND METHODS OF THEIR USE
  申请人：Signal Pharmaceuticals, LLC

  公开号：US20130142873A1

  公开（公告）日：2013-06-06

  Provided herein are compositions of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, solid forms, isotopologues and metabolites thereof, and methods of their use for the treatment of a disease, disorder, or condition.

  本文提供了7-(6-(2-羟基丙醇基)吡啶-3-基)-1-((反式)-4-甲氧基环己基)-3,4-二氢吡嗪[2,3-b]吡嗪-2(1H)-酮的组合物、固态形式、同位素及其代谢物，并且提供了它们用于治疗疾病、疾病或症状的方法。
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