methyl 3-amino-4-(2-methoxyphenyl)-2-thiophene carboxylate | 679425-84-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: methyl 3-amino-4-(2-methoxyphenyl)-2-thiophene carboxylate
• 英文别名: methyl 3-amino-4-(2-methoxyphenyl)thiophene-2-carboxylate；methyl 3-amino-4-(2-methoxyphenyl)-2-thiophenecarboxylate
• CAS: 679425-84-4
• 化学式: C₁₃H₁₃NO₃S
• 分子量: 263.317
• InChiKey: OIFNCEWJVSHUMD-UHFFFAOYSA-N

物化性质

• 熔点：
  110-111 °C
• 沸点：
  381.7±42.0 °C(Predicted)
• 密度：
  1.263±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  89.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-amino-4-(2-methoxyphenyl)-2-thiophene carboxylate 在 4-氯吡啶盐酸盐 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.75h， 生成 4-(2-methoxyphenyl)-3-(pyrrol-1-yl)thien-2-ylpyrrolidine carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel Thienopyrrolizinones as Antitubulin Agents

  摘要：

  Herein, we describe the structure-activity relationship study of a new 3-aryl-8H-thieno[2,3-b]pyrrolizin-8-one series of antitubulin agents. The pharmacological results from the National Cancer Institute in vitro human disease oriented tumor cell line screening allowed us to identify compound 1d (NSC 676693) as a very efficient antitumoral drug in all cancer cell lines tested. This prompted us to define the structural requirements essential for this antiproliferative activity. Among all analogues synthesized in this study, compound 1o was the most promising, being 10-fold more potent than compound 1d. Its activity over a panel of nine tumoral cell lines was in the nanomolar range for all of the histological types tested, and surprisingly, the resistant KB-A1 cell line was also sensitive to this compound. Moreover, a flow cytometric study showed that L1210 cells treated by the most potent compounds were arrested in the G(2)/M phases of the cell cycle with a significant percentage of cells having reinitiated a cycle of DNA synthesis without cell division. This interesting pharmacological profile, resulting from inhibition of tubulin polymerization, encouraged us to perform preliminary in vivo studies that led to a new prodrug chemical approach.

  DOI：

  10.1021/jm030961z
• 作为产物：
  描述：

  邻甲氧基苯乙腈 在 sodium methylate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 3-amino-4-(2-methoxyphenyl)-2-thiophene carboxylate
  参考文献：
  名称：

  N 3-烷基-噻吩并嘧啶-4-酮作为mGluR1拮抗剂的合成及生物评价

  摘要：

  代谢型谷氨酸受体亚型1（mGluR1）是治疗神经性疼痛的潜在靶标，并且已经进行了很多努力来发现mGluR1拮抗剂。在这项研究中，通过将各种烷基和芳基分别引入到噻吩并嘧啶-4-酮核心结构的N 3和7位上，制备了一系列N 3-烷基噻吩并嘧啶-4-酮及其抑制作用。对mGluR1的活性进行了生物学评估。结构-活性关系研究表明，N 3处的反式-4-甲基环己基，环庚基和环辛基 位和2位的2-氟苯基最有效地增强噻吩并嘧啶4-1衍生物对mGluR1的抑制活性。在合成的化合物中，3-环辛基-7-苯基噻吩并嘧啶丁-4-和3-环庚基-7-（2-氟苯基）噻吩并嘧啶丁4-1表现出最强的抑制活性，IC 50值分别为115和107 nM。 。

  DOI：

  10.1002/bkcs.10283

文献信息

• THIENOPYRIMIDINONE DERIVATIVES AS mGluR1 ANTAGONISTS
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY

  公开号：US20140228565A1

  公开（公告）日：2014-08-14

  Disclosed are thienopyrimidinone derivatives as antagonists that act on metabotropic glutamate receptor subtype 1. The thienopyrimidinone derivatives show pharmacological activity against metabotropic glutamate receptor-related diseases, including pain, such as neuropathic pain and migraine, psychiatric diseases, such as anxiety disorder and schizophrenia, urinary incontinence, and neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Also disclosed are methods for preparing the thienopyrimidinone derivatives, and pharmaceutical compositions containing the thienopyrimidinone derivatives as active ingredients.

  披露了作为对代谢型谷氨酸受体亚型1起作用的拮抗剂的噻吩嘧啶酮衍生物。这些噻吩嘧啶酮衍生物显示出对代谢型谷氨酸受体相关疾病的药理活性，包括疼痛，如神经病性疼痛和偏头痛，精神疾病，如焦虑症和精神分裂症，尿失禁，以及神经退行性疾病，如帕金森病和阿尔茨海默病。还披露了制备这些噻吩嘧啶酮衍生物的方法，以及含有这些噻吩嘧啶酮衍生物作为活性成分的药物组合物。
• 8H-thieno-[2,3-b]pyrrolizin-8-one compounds
  申请人：Adir et Compagnie

  公开号：US06071945A1

  公开（公告）日：2000-06-06

  A compound selected from those of formula (I): ##STR1## wherein: R.sub.1 represents hydrogen, halogen, alkyl, nitro, hydroxy, alkoxy, trihaloalkyl, trihaloalkoxy or optionally substituted amino, R.sub.2 represents optionally substituted aryl or heteroaryl, R.sub.3 represents hydrogen, halogen, alkyl, nitro, hydroxy, alkoxy, trihaloalkyl, trihaloalkoxy or optionally substituted amino, their isomers and addition pharmaceutically-acceptable acid or base salts thereof and medicinal products containing the same are useful in the treatment of cancer.

  公式（I）中选择的化合物：##STR1## 其中：R.sub.1代表氢，卤素，烷基，硝基，羟基，烷氧基，三卤代烷基，三卤代烷氧基或可选取代氨基，R.sub.2代表可选取代的芳基或杂环基，R.sub.3代表氢，卤素，烷基，硝基，羟基，烷氧基，三卤代烷基，三卤代烷氧基或可选取代氨基，它们的异构体和药学上可接受的酸或碱盐以及含有它们的药物制品在癌症治疗中有用。
• Thienopyrimidinone derivatives as mGluR1 antagonists
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY

  公开号：US09260448B2

  公开（公告）日：2016-02-16

  Disclosed are thienopyrimidinone derivatives as antagonists that act on metabotropic glutamate receptor subtype 1. The thienopyrimidinone derivatives show pharmacological activity against metabotropic glutamate receptor-related diseases, including pain, such as neuropathic pain and migraine, psychiatric diseases, such as anxiety disorder and schizophrenia, urinary incontinence, and neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Also disclosed are methods for preparing the thienopyrimidinone derivatives, and pharmaceutical compositions containing the thienopyrimidinone derivatives as active ingredients.

  本发明涉及噻唑嘧啶酮衍生物，作为代谢型谷氨酸受体亚型1的拮抗剂。该噻唑嘧啶酮衍生物对代谢型谷氨酸受体相关疾病具有药理活性，包括疼痛，如神经病性疼痛和偏头痛，精神疾病，如焦虑症和精神分裂症，尿失禁以及神经退行性疾病，如帕金森病和阿尔茨海默病。本发明还涉及制备噻唑嘧啶酮衍生物的方法，以及含有该噻唑嘧啶酮衍生物作为活性成分的药物组合物。
• Novel thienopyrimidinones as mGluR1 antagonists
  作者：Youngjae Kim、Jeeyeon Kim、Sora Kim、Yooran Ki、Seon Hee Seo、Jinsung Tae、Min Kyung Ko、Hyun-Seo Jang、Eun Jeong Lim、Chiman Song、YoonJeong Cho、Hae-Young Koh、Youhoon Chong、Il Han Choo、Gyochang Keum、Sun-Joon Min、Hyunah Choo

  DOI：10.1016/j.ejmech.2014.08.027

  日期：2014.10

  There has been much attention to discover mGluR1 antagonists for treating various central nervous system diseases such as seizures and neuropathic pain. Thienopyrimidinone derivatives were designed, synthesized, and biologically evaluated against mGluR1. Among the synthesized compounds, 3-(4-methoxyphenyl)-7-(o-tolyl)thienopyrimidin-4-one 30 exhibited the most potent inhibitory activity with an IC50 value of 45 nM and good selectivity over mGluR5. Also, the selective mGluR1 antagonist 30 showed marginal hERG channel activity (IC50 = 9.87 mu M), good profiles to CYP isozymes, and a good pharmacokinetic profile. Overall, the compound 30 was identified as a selective mGluR1 antagonist with a good pharmacokinetic profile, which is probably devoid of cardiac side effect and drug drug interactions. Therefore, the compound 30 can be expected to be broadly used as mGluR1 antagonistic chemical probe in in vitro and in vivo study for investigating CNS diseases. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Design, synthesis and antiproliferative activity of tripentones: A new series of antitubulin agents
  作者：Vincent Lisowski、Cécile Enguehard、Jean-Charles Lancelot、Daniel-Henri Caignard、Stéphanie Lambel、Stéphane Leonce、Alain Pierre、Ghanem Atassi、Pierre Renard、Sylvain Rault

  DOI：10.1016/s0960-894x(01)00403-6

  日期：2001.8

  Structure-activity relationship studies of a new series of tripentones (thieno[2.3-h]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2.3-b]pyrrolizin-8-one 20 (leukemia L1210. IC50= 15 nM) was shown to be a potent inhibitor of tubulin polymerization. (C) 2001 Elsevier Science Ltd. All rights reserved.