6-iodo-4(3H)-oxo-2-pivaloylamino-7H-pyrrolo<2,3-d>pyrimidine | 143682-15-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 6-iodo-4(3H)-oxo-2-pivaloylamino-7H-pyrrolo<2,3-d>pyrimidine
• 英文别名: 2-pivaloyl-8-iodo-7-deazaguanidine；N-(6-iodo-4-oxo-3,7-dihydropyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropanamide
• CAS: 143682-15-9
• 化学式: C₁₁H₁₃IN₄O₂
• 分子量: 360.154
• InChiKey: XSNKTBDFEUCIJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  86.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-iodo-4(3H)-oxo-2-pivaloylamino-7H-pyrrolo<2,3-d>pyrimidine 在 platinum(IV) oxide copper(l) iodide 、 四(三苯基膦)钯 、 氢气 、 sodium hydride 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、399.9 kPa 条件下， 反应 27.5h， 生成 4-{2-[2-(2,2-Dimethyl-propionylamino)-4-oxo-7-(toluene-4-sulfonyl)-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl]-ethyl}-benzoic acid methyl ester
  参考文献：
  名称：

  Synthesis of N-{4-[2-(2-Amino-5,6-dihydro-4(3H)-oxo-7H-pyrrolo[2,3-d]pyrimidin-6-yl)- ethyl]benzoyl}-l-glutamic Acid:  A Ring-Contracted Analogue of 5,10-Dideaza-5,6,7,8-tetrahydrofolic Acid

  摘要：

  This paper describes the synthesis of N-(4-[2-(2-amino-5,6-dihydro-4(3H)-oxo-7H-pyrrolo[2,3-d]-pyrimidin-6-yl)ethyl]benzoyl) -L-glutamic acid (4), which can be viewed as a ring-contracted analogue of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF, 1) in which the C-7 methylene group of the latter has been excised and C-6 joined to N-8. This compound exhibits significant activity as an inhibitor of the growth of human (CCRF-CEM) lymphoblastic leukemic cells in vitro and apparently acts by blocking de novo purine biosynthesis through inhibition of glycinamide ribonucleotide formyltransferase (GAR FTase).

  DOI：

  10.1021/jo951471k
• 作为产物：
  描述：

  N-(4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)pivalamide 在 mercury(II) diacetate 、 碘 、 溶剂黄146 作用下， 生成 2-pivaloylamino-4(3H)-oxo-5-iodo-7H-pyrrolo<2,3-d>pyrimidine 、 6-iodo-4(3H)-oxo-2-pivaloylamino-7H-pyrrolo<2,3-d>pyrimidine
  参考文献：
  名称：

  Taylor, Edward C.; Young, Wendy B.; Chaudhari, Rajendra, Heterocycles, 1993, vol. 36, # 8, p. 1897 - 1908

  摘要：

  DOI：

文献信息

• 2-amino-4-oxo-6-substituted-pyrrolo[2,3-<i>d</i>]pynmidines as potential inhibitors of thymidylate synthase
  作者：Aleem Gangjee、Jianming Yu、Roy L. Kisliuk

  DOI：10.1002/jhet.5570390433

  日期：2002.7

  in the synthesis and evaluation of nonclassical inhibitors, which could enter cells via passive diffusion and are not substrates for folypolyglutamate synthetase. A series of eight nonclassical 6-substituted 2-amino-4-oxo-pyrrolo[2,3-d]pyrimidines 2a-2h were designed as potential inhibitors of thymidylate synthase. The synthesis of the target compounds 2a-2h was achieved via regioselective iodination

  当用作抗肿瘤剂时，胸苷酸合酶的经典抗叶酸抑制剂通常具有许多潜在的缺点。这些包括由于细胞吸收所需的主动转运系统的改变而导致的吸收受损，以及通过对谷胱甘肽合成酶负责的长效非流出型聚谷氨酸酯的形成，这对正常细胞具有毒性。为了克服经典的胸苷酸合酶抑制剂的一些缺点，人们对非经典抑制剂的合成和评估有了相当大的兴趣，这些抑制剂可以通过被动扩散进入细胞，而不是草氨酸谷氨酸合成酶的底物。一系列八个非经典的6-取代的2-氨基-4-氧代-吡咯烷[2,3- d]嘧啶2a-2h被设计为胸苷酸合酶的潜在抑制剂。目标化合物2a-2h的合成是通过在5的6位上进行区域选择性碘化，钯催化与适当的苯乙炔的偶联，还原C8-C9三键，然后进行皂化来实现的。初步生物学结果表明，在测试浓度下，目标化合物均未显示出对大肠杆菌，干酪乳杆菌，大鼠或人胸苷酸合酶的胸苷酸合酶的抑制活性。目标化合物均未显示对大肠杆菌，干酪乳杆菌的二氢叶酸还原酶具有抑制活性，大鼠或人在3
• N2-Trimethylacetyl substituted and unsubstituted-N4-phenylsubstituted-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines: Design, cellular receptor tyrosine kinase inhibitory activities and in vivo evaluation as antiangiogenic, antimetastatic and antitumor agents
  作者：Aleem Gangjee、Ojas A. Namjoshi、Jianming Yu、Michael A. Ihnat、Jessica E. Thorpe、Lora C. Bailey-Downs

  DOI：10.1016/j.bmc.2012.12.045

  日期：2013.3

  Six novel N-4-phenylsubstituted-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines and their N-2-trimethylacetyl substituted analogs were synthesized as receptor tyrosine kinase (RTK) inhibitors. A microwave-mediated Sonogashira reaction was used as a key step for the synthesis of these compounds. Biological evaluation, in whole cell assays, showed that some analogs had remarkable inhibitory activity against a variety of RTKs and in particular cytotoxic activity against A431 tumor cells in culture. The inhibitory data against RTKs in this study demonstrated that variation of the 4-anilino substituents of these analogs dictates both potency and specificity of inhibitory activity against various RTKs. The study also supported the hypothesis that interaction of substituents on the 2-amino group with hydrophobic site-II provides an increase in potency. Compound 8 of this series was selected for evaluation in vivo in a B16-F10 syngeneic mouse tumor model and exhibited significant reduction in tumor growth rate, in tumor vascular density and in metastases to the lung compared to the control. (C) 2013 Elsevier Ltd. All rights reserved.
• Taylor, Edward C.; Young, Wendy B.; Chaudhari, Rajendra, Heterocycles, 1993, vol. 36, # 8, p. 1897 - 1908
  作者：Taylor, Edward C.、Young, Wendy B.、Chaudhari, Rajendra、Patel, Hemantkumar H.

  DOI：——

  日期：——
• Synthesis of <i>N</i>-{4-[2-(2-Amino-5,6-dihydro-4(3<i>H</i>)-oxo-7<i>H</i>-pyrrolo[2,3-<i>d</i>]pyrimidin-6-yl)- ethyl]benzoyl}-<scp>l</scp>-glutamic Acid:  A Ring-Contracted Analogue of 5,10-Dideaza-5,6,7,8-tetrahydrofolic Acid
  作者：Edward C. Taylor、Wendy B. Young、Carsten Spanka

  DOI：10.1021/jo951471k

  日期：1996.1.1

  This paper describes the synthesis of N-(4-[2-(2-amino-5,6-dihydro-4(3H)-oxo-7H-pyrrolo[2,3-d]-pyrimidin-6-yl)ethyl]benzoyl) -L-glutamic acid (4), which can be viewed as a ring-contracted analogue of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF, 1) in which the C-7 methylene group of the latter has been excised and C-6 joined to N-8. This compound exhibits significant activity as an inhibitor of the growth of human (CCRF-CEM) lymphoblastic leukemic cells in vitro and apparently acts by blocking de novo purine biosynthesis through inhibition of glycinamide ribonucleotide formyltransferase (GAR FTase).