2-噻吩羧酸,4-(4-羟基丁基)-,甲基酯 | 130073-86-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 中文名称: 2-噻吩羧酸,4-(4-羟基丁基)-,甲基酯
• 英文名称: 4-(4-hydroxybutyl)thiophene-2-carboxylic acid methyl ester
• 英文别名: methyl 4-(4-hydroxybutyl)thiophene-2-carboxylate；methyl 4-(4-hydroxybutyl)thien-2-ylcarboxylate；4-(4-Hydroxy-butyl)-thiophene-2-carboxylic acid methyl ester
• CAS: 130073-86-8
• 化学式: C₁₀H₁₄O₃S
• 分子量: 214.285
• InChiKey: WWRYNHDSHKCBOG-UHFFFAOYSA-N

物化性质

• 沸点：
  351.8±37.0 °C(Predicted)
• 密度：
  1.189±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  74.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-噻吩羧酸,4-(4-羟基丁基)-,甲基酯 在 N-甲基吗啉 、 sodium hydroxide 、 sodium methylate 、 sodium hydride 、 三乙胺 、 N-苯基磷氨基氯化苯 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 52.5h， 生成 N-<4-<4-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)butyl>-2-thienyl>-L-glutamic acid
  参考文献：
  名称：

  5,10-dideaza-5,6,7,8-四氢叶酸的无环类似物的合成和生物活性。

  摘要：

  N- [4- [4-（2,4-二氨基-1,6-二氢-6-氧代-5-嘧啶基）丁基]苯甲酰基] -L-谷氨酸的许多类似物的合成和生物学评价2）（7-DM-DDATHF），描述了新型叶酸抗代谢物5,10-二叠氮基四氢叶酸（DDATHF）的无环修饰。以前用于合成2、15和16的合成方法扩展到制备在苯甲酰基区域被噻吩和亚甲基取代的苯环（化合物27a-c）和谷氨酸区域被天冬氨酸修饰的类似物。用苯丙氨酸代替L-谷氨酸（化合物36、37）。2-氨基-4,6-二氧羰基衍生物33是由中间体30与（4-碘苯甲酰基）-L-谷氨酸二乙酯经钯催化的碳-碳偶合反应制得的，然后用碱还原和除去保护基。所有以上DDATHF的无环类似物对CCRF-CEM人淋巴母细胞白血病细胞的细胞培养细胞毒性研究均得出IC50值范围大于0.042（大于48 microM）。对分离的酶的抑制和细胞培养逆转研究表明了这些化合物的作用方式。化合物2

  DOI：

  10.1021/jm00084a016
• 作为产物：
  描述：

  4-溴噻吩-2-甲酸甲酯 在 copper(l) iodide 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 三苯基膦 、 palladium dichloride 作用下， 以 甲醇 、 乙腈 为溶剂， 100.0 ℃ 、379.22 kPa 条件下， 反应 10.0h， 生成 2-噻吩羧酸,4-(4-羟基丁基)-,甲基酯
  参考文献：
  名称：

  6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Targeted Antifolates for Folate Receptor α and the Proton-Coupled Folate Transporter in Human Tumors

  摘要：

  2-Amino-4-oxo-6-substituted-pyrrolo[2,3-d] pyrimidine antifolate thiophene regioisomers of AGF94 (4) with a thienoyl side chain and three-carbon bridge lengths [AGF150 (5) and AGF154 (7)] were synthesized as potential antitumor agents. These analogues inhibited proliferation of Chinese hamster ovary (CHO) sublines expressing folate receptors (FRs) alpha or beta (IC(50)s < 1 nM) or the proton-coupled folate transporter (PCFT) (IC50 < 7 nM). Compounds 5 and 7 inhibited KB, IGROV1, and SKOV3 human tumor cells at subnanomolar concentrations, reflecting both FR alpha and PCFT uptake. AGF152 (6) and AGF163 (8), 2,4-diamino-5-substituted-furo[2,3-d]pyrimidine thiophene regioisomers, also inhibited growth of FR-expressing CHO and KB cells. All four analogues inhibited glycinamide ribonucleotide formyltransferase (GARFTase). Crystal structures of human GARFTase complexed with 5 and 7 were reported. In severe combined immunodeficient mice bearing SKOV3 tumors, 7 was efficacious. The selectivity of these compounds for PCFT and for FR alpha and beta over the ubiquitously expressed reduced folate carrier is a paradigm for selective tumor targeting.

  DOI：

  10.1021/acs.jmedchem.5b00801

文献信息

• L-glutamic acid derivatives
  申请人：The Trustees of Princeton University

  公开号：US04920125A1

  公开（公告）日：1990-04-24

  Pyrimidin-5-yl derivatives of L-glutamic acid are anti-neoplastic agents. A typical embodiment is N-(4-[5-(2,6-diamino-4-hydroxypyrimidin-5-yl)-butyl]-thien-2-ylcarboxy)-L- glutamic acid.

  吡咯嗪-5-基L-谷氨酸衍生物是抗肿瘤药物。一个典型的实施例是N-(4-[5-(2,6-二氨基-4-羟基嘧啶-5-基)-丁基]-噻吩-2-基羧基)-L-谷氨酸。
• 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。
• TAYLOR, EDWARD C.;HARRINGTON, PHILIP M.;SHIH, CHUAN
  作者：TAYLOR, EDWARD C.、HARRINGTON, PHILIP M.、SHIH, CHUAN

  DOI：——

  日期：——
• US4920125A
  申请人：——

  公开号：US4920125A

  公开（公告）日：1990-04-24
• [EN] SELECTIVE PROTON COUPLED FOLATE TRANSPORTER AND FOLATE RECEPTOR, AND GARFTASE AND/OR OTHER FOLATE METABOLIZING ENZYMES INHIBITOR COMPOUNDS AND METHODS OF USING THE SAME<br/>[FR] TRANSPORTEUR SÉLECTIF DE FOLATES COUPLÉS AUX PROTONS ET RÉCEPTEUR DES FOLATES, ET GARFTASE ET/OU AUTRES COMPOSÉS INHIBITEURS D'ENZYMES MÉTABOLISANT LES FOLATES ET PROCÉDÉS D'UTILISATION DE CEUX-CI
  申请人：UNIV HOLY GHOST DUQUESNE

  公开号：WO2012051105A2

  公开（公告）日：2012-04-19

  The present invention provides selective proton coupled folate transporter and folate receptor, and glycinamide ribonucleotide formyltransferase enzyme and/or other folate metabolizing enzyme inhibitors having a fused cyclic pyrimidine compound, including tautomers thereof, and pharmaceutically acceptable salts, prodrugs, solvates and hydrates thereof. 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.