(S)-2-[(3-bromothiophene-2-carbonyl)amino]pentanedioic acid diethyl ester | 1286279-52-4

• 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-[(3-bromothiophene-2-carbonyl)amino]pentanedioic acid diethyl ester
• 英文别名: diethyl (2S)-2-[(3-bromothiophene-2-carbonyl)amino]pentanedioate
• CAS: 1286279-52-4
• 化学式: C₁₄H₁₈BrNO₅S
• 分子量: 392.271
• InChiKey: WFUJOWAXWDTMDU-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-[(3-bromothiophene-2-carbonyl)amino]pentanedioic acid diethyl ester 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 (S)-2-({3-[4-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]-pyrimidin-6-yl)but-1-ynyl]thiophene-2-carbonyl}amino)-pentanedioic acid
  参考文献：
  名称：

  Synthesis and Biological Activity of 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Inhibitors of de Novo Purine Biosynthesis with Selectivity for Cellular Uptake by High Affinity Folate Receptors and the Proton-Coupled Folate Transporter over the Reduced Folate Carrier

  摘要：

  We previously reported the selective transport of classical 2-amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidines with a thienoyl-for-benzoyl-substituted side chain and a three- (3a) and four-carbon (313) bridge. Compound 3a was more potent than 3b against tumor cells. While 3b was completely selective for transport by folate receptors (FRs) and the proton-coupled folate transporter (PCFT) over the reduced folate carrier (RFC), 3a was not. To determine if decreasing the distance between the bicyclic scaffold and L-glutamate in 3b would preserve transport selectivity and potency against human tumor cells, 3b regioisomers with [1,3] (7 and 8) and [1,2] (4, 5, and 6) substitutions on the thienoyl ring and with acetylenic insertions in the four-atom bridge were synthesized and evaluated. Compounds 7 and 8 were potent nanomolar inhibitors of KB and IGROV1 human tumor cells with complete selectivity for FR alpha and PCFT over RFC.

  DOI：

  10.1021/jm201688n
• 作为产物：
  描述：

  3-溴噻吩-2-甲酸 、 L-谷氨酸二乙酯盐酸盐 在 N-甲基吗啉 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.5h， 以91%的产率得到(S)-2-[(3-bromothiophene-2-carbonyl)amino]pentanedioic acid diethyl ester
  参考文献：
  名称：

  Synthesis and Biological Activity of 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Inhibitors of de Novo Purine Biosynthesis with Selectivity for Cellular Uptake by High Affinity Folate Receptors and the Proton-Coupled Folate Transporter over the Reduced Folate Carrier

  摘要：

  We previously reported the selective transport of classical 2-amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidines with a thienoyl-for-benzoyl-substituted side chain and a three- (3a) and four-carbon (313) bridge. Compound 3a was more potent than 3b against tumor cells. While 3b was completely selective for transport by folate receptors (FRs) and the proton-coupled folate transporter (PCFT) over the reduced folate carrier (RFC), 3a was not. To determine if decreasing the distance between the bicyclic scaffold and L-glutamate in 3b would preserve transport selectivity and potency against human tumor cells, 3b regioisomers with [1,3] (7 and 8) and [1,2] (4, 5, and 6) substitutions on the thienoyl ring and with acetylenic insertions in the four-atom bridge were synthesized and evaluated. Compounds 7 and 8 were potent nanomolar inhibitors of KB and IGROV1 human tumor cells with complete selectivity for FR alpha and PCFT over RFC.

  DOI：

  10.1021/jm201688n

文献信息

• SELECTIVE PROTON COUPLED FOLATE TRANSPORTER AND FOLATE RECEPTOR, AND GARFTASE AND/OR OTHER FOLATE METABOLIZING ENZYMES INHIBITOR COMPOUNDS AND METHODS OF USING THE SAME
  申请人：Gangjee Aleem

  公开号：US20110082158A1

  公开（公告）日：2011-04-07

  Fused cyclic pyrimidine compounds, including tautomers thereof, and pharmaceutically acceptable salts, prodrugs, solvates and hydrates thereof, are disclosed having the general Formula II: These compounds are useful in methods for treating cancer, selectively targeting cancerous cells via the proton coupled folate transporter, folate receptor alpha, and/or folate receptor beta pathways, inhibiting GARFTase and/or other folate metabolizing enzymes in cancerous cells, and selectively targeting activated macrophages in a patient having an autoimmune disease, such as rheumatoid arthritis.

  本发明公开了融合的环状嘧啶化合物（包括其互变异构体）及其药学上可接受的盐、前药、溶剂化物和水合物，其具有通用式II：这些化合物在治疗癌症的方法中有用，通过质子耦合叶酸转运体、叶酸受体α和/或叶酸受体β途径选择性地靶向癌细胞，抑制癌细胞中的GARFT酶和/或其他叶酸代谢酶，并选择性地靶向患有自身免疫疾病（如类风湿性关节炎）的患者中的活化巨噬细胞。
• Synthesis and Biological Activity of 6-Substituted Pyrrolo[2,3-<i>d</i>]pyrimidine Thienoyl Regioisomers as Inhibitors of de Novo Purine Biosynthesis with Selectivity for Cellular Uptake by High Affinity Folate Receptors and the Proton-Coupled Folate Transporter over the Reduced Folate Carrier
  作者：Lei Wang、Christina Cherian、Sita Kugel Desmoulin、Shermaine Mitchell-Ryan、Zhanjun Hou、Larry H. Matherly、Aleem Gangjee

  DOI：10.1021/jm201688n

  日期：2012.2.23

  We previously reported the selective transport of classical 2-amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidines with a thienoyl-for-benzoyl-substituted side chain and a three- (3a) and four-carbon (313) bridge. Compound 3a was more potent than 3b against tumor cells. While 3b was completely selective for transport by folate receptors (FRs) and the proton-coupled folate transporter (PCFT) over the reduced folate carrier (RFC), 3a was not. To determine if decreasing the distance between the bicyclic scaffold and L-glutamate in 3b would preserve transport selectivity and potency against human tumor cells, 3b regioisomers with [1,3] (7 and 8) and [1,2] (4, 5, and 6) substitutions on the thienoyl ring and with acetylenic insertions in the four-atom bridge were synthesized and evaluated. Compounds 7 and 8 were potent nanomolar inhibitors of KB and IGROV1 human tumor cells with complete selectivity for FR alpha and PCFT over RFC.