(S)-2-(5-(2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)thiophene-2-carboxamido)pentanedioic acid

• 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: (S)-2-(5-(2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)thiophene-2-carboxamido)pentanedioic acid
• 英文别名: (2S)-2-[[5-[2-(2-amino-4-oxo-3,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]thiophene-2-carbonyl]amino]pentanedioic acid
• 化学式: C₁₈H₁₉N₅O₆S
• 分子量: 433.445
• InChiKey: CTSPVOIVQCLQLX-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  215
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  methyl 5-(4-oxobutyl)thiophene-2-carboxylate 在 N-甲基吗啉 、 盐酸 、 甲醇 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 、 5,5-二溴-2,2-二甲基-4,6-二酮-1,3-二氧杂环己烷 、 sodium acetate 、 sodium hydroxide 作用下， 以 甲醇 、 乙醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 59.0h， 生成 (S)-2-(5-(2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)thiophene-2-carboxamido)pentanedioic acid
  参考文献：
  名称：

  Novel 5-Substituted Pyrrolo[2,3-d]pyrimidines as Dual Inhibitors of Glycinamide Ribonucleotide Formyltransferase and 5-Aminoimidazole-4-carboxamide Ribonucleotide Formyltransferase and as Potential Antitumor Agents

  摘要：

  A new series of 5-substituted thiopheneyl pyrrolo[2,3-d]pyrimidines 6-11 with varying chain lengths (n = 1-6) were designed and synthesized as hybrids of the clinically used anticancer drug pemetrexed (PMX) and our 6-substituted thiopheneyl pyrrolo[2,3-d]pyrimidines 2c and 2d with folate receptor (FR) a and proton-coupled folate transporter (PCFT) uptake specificity over the reduced folate carrier (RFC) and inhibition of de novo purine nucleotide biosynthesis at glycinamide ribonucleotide formyltransferase (GARFTase). Compounds 6-11 inhibited KB human tumor cells in the order 9 = 10 > 8 > 7 > 6 = 11. Compounds 8-10 were variously transported by FRa, PCFT, and RFC and, unlike PMX, inhibited de novo purine nucleotide rather than thymidylate biosynthesis. The antiproliferative effects of 8 and 9 appeared to be due to their dual inhibitions of both GARFTase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase. Our studies identify a unique structure-activity relationship for transport and dual target inhibition.

  DOI：

  10.1021/jm501787c

文献信息

• Pyrrolopyrimidines, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0418924A2

  公开（公告）日：1991-03-27

  A compound of the formula (I): wherein the ring Ⓐ is a pyrrole ring which may be hydrogenated, X is an amino group, a hydroxyl group or a mercapto group, Y is a hydrogen atom or a hydroxyl group, -COOR¹ and -COOR² may be the same or different and are a carboxyl group which may be esterified, -Ⓑ- is a divalent heterocyclic group or a lower alkylene group each of which may be substituted, and Z is a straight C₂₋₄ divalent group which may be substituted, or its salt, a method for the production of the same and an antitumor agent containing the same.

  式(I)的化合物： 其中环 Ⓐ是可以氢化的吡咯环，X 是氨基、羟基或巯基，Y 是氢原子或羟基，-COOR¹ 和 -COOR² 可以相同或不同，是可以酯化的羧基、-Ⓑ-是二价杂环基团或低级亚烷基，每个基团均可被取代，Z是可被取代的直C₂₋₄二价基团或其盐，以及生产这种物质的方法和含有这种物质的抗肿瘤剂。
• US5354754A
  申请人：——

  公开号：US5354754A

  公开（公告）日：1994-10-11
• Novel 5-Substituted Pyrrolo[2,3-<i>d</i>]pyrimidines as Dual Inhibitors of Glycinamide Ribonucleotide Formyltransferase and 5-Aminoimidazole-4-carboxamide Ribonucleotide Formyltransferase and as Potential Antitumor Agents
  作者：Yiqiang Wang、Shermaine Mitchell-Ryan、Sudhir Raghavan、Christina George、Steven Orr、Zhanjun Hou、Larry H. Matherly、Aleem Gangjee

  DOI：10.1021/jm501787c

  日期：2015.2.12

  A new series of 5-substituted thiopheneyl pyrrolo[2,3-d]pyrimidines 6-11 with varying chain lengths (n = 1-6) were designed and synthesized as hybrids of the clinically used anticancer drug pemetrexed (PMX) and our 6-substituted thiopheneyl pyrrolo[2,3-d]pyrimidines 2c and 2d with folate receptor (FR) a and proton-coupled folate transporter (PCFT) uptake specificity over the reduced folate carrier (RFC) and inhibition of de novo purine nucleotide biosynthesis at glycinamide ribonucleotide formyltransferase (GARFTase). Compounds 6-11 inhibited KB human tumor cells in the order 9 = 10 > 8 > 7 > 6 = 11. Compounds 8-10 were variously transported by FRa, PCFT, and RFC and, unlike PMX, inhibited de novo purine nucleotide rather than thymidylate biosynthesis. The antiproliferative effects of 8 and 9 appeared to be due to their dual inhibitions of both GARFTase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase. Our studies identify a unique structure-activity relationship for transport and dual target inhibition.