2-氨基-4-乙基-5-甲基噻吩-3-羧酸甲酯 | 4815-25-2

• 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-氨基-4-乙基-5-甲基噻吩-3-羧酸甲酯
• 中文别名: 2-氨基-4-乙基-5-甲基-3-噻吩羧酸甲酯
• 英文名称: methyl 2-amino-4-ethyl-5-methylthiophene-3-carboxylate
• CAS: 4815-25-2
• 化学式: C₉H₁₃NO₂S
• mdl: MFCD00781744
• 分子量: 199.274
• InChiKey: ODDNCALHGKYZJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H312,H315,H319,H332,H335
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  2-氨基-4-乙基-5-甲基噻吩-3-羧酸甲酯 在 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 、 水 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 27.0h， 生成 n-propyl 4-ethyl-5-methyl-2-[((4-methylphenyl)carbonyl)-amino]thiophene-3-carboxylate
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of 2-(Acylamino)thiophene Derivatives as Metabolically Stable, Orally Effective, Positive Allosteric Modulators of the GABA_B Receptor

  摘要：

  Two recently reported hit compounds, COR627 and COR628, underpinned the development of a series of 2-(acylamino)thiophene derivatives. Some of these compounds displayed significant activity in vitro as positive allosteric modulators of the GABA(B) receptor by potentiating GTP gamma S stimulation induced by GABA at 2.5 and 25 mu M while failing to exhibit intrinsic agonist activity. Compounds were also found to be effective in vivo, potentiating baclofen-induced sedation/hypnosis in DBA mice when administered either intraperitoneally or intragastrically. Although displaying a lower potency in vitro than the reference compound GS39783, the new compounds 6, 10, and 11 exhibited a higher efficacy in vivo: combination of these compounds with a per se nonsedative dose of baclofen resulted in shorter onset and longer duration of the loss of righting reflex in mice. Test compounds showed cytotoxic effects at concentrations comparable to or higher than those of GS39783 or BHF177.

  DOI：

  10.1021/jm400144w
• 作为产物：
  描述：

  3-戊酮 、 氰乙酸甲酯 在 吗啉 、 1,2,3,4,5,6,7,8-八硫杂环辛烷 作用下， 以 甲醇 为溶剂， 生成 2-氨基-4-乙基-5-甲基噻吩-3-羧酸甲酯
  参考文献：
  名称：

  新型2-（1-金刚烷基羧酰胺基）噻吩衍生物的合成。选择性大麻素2型（CB2）受体激动剂可作为治疗皮肤炎性疾病的潜在药物

  摘要：

  合成了一组基于噻吩骨架的CB2R配体，并在体外分析中进行了评估。在噻吩环的5-位或4-和5-位带有3-羧酸根和2-（金刚烷-1-基）羧酰胺基以及非极性烷基/芳基取代基的化合物8c-i，k，l具有在低纳摩尔浓度下具有高CB2R亲和力，良好的受体选择性和激动性功能活性。在过敏性接触性皮炎的实验模型中对全受体激动剂8g（在受体亲和力和选择性之间取得了最佳平衡）进行了体外测试，结果证明能够以10μM的浓度阻断HaCaT细胞中MCP-2的释放。

  DOI：

  10.1016/j.ejmech.2018.09.070

文献信息

• The GABAB receptor positive allosteric modulator COR659: In vitro metabolism, in vivo pharmacokinetics in rats, synthesis and pharmacological characterization of metabolically protected derivatives
  作者：Francesca Ferlenghi、Paola Maccioni、Claudia Mugnaini、Antonella Brizzi、Federica Fara、Rafaela Mostallino、M Paola Castelli、Giancarlo Colombo、Marco Mor、Federica Vacondio、Federico Corelli

  DOI：10.1016/j.ejps.2020.105544

  日期：2020.12

  vivo. M1, cleavage product of the methyl ester group at C-3, revealed in vitro an unusual mechanism of metabolism by a NADPH-dependent route and, in vivo, it maintained high and persistent levels in plasma, which could represent a potential pharmacokinetic and toxicological issue. In the novel set of COR659 analogues, those bearing branched alkyl substituents on the ester group, showed an improved in vitro

  我们报告了一项对COR659（1）的体外I期代谢研究，COR659是一种2-酰基氨基噻吩衍生物，能够抑制大鼠酒精和巧克力的自我给药，可能是通过对GABA B受体的正变构调节和对大麻素的拮抗作用/反向激动作用CB 1受体。鉴于已将噻吩环C-3处的甲基酯基团鉴定为代谢弱点，我们还报告了化学优化项目，旨在平衡一组3取代COR659类似物在体内和体外的代谢稳定性与代谢稳定性。 高效液相色谱串联和高分辨率质谱用于表征大鼠COR659的体外代谢和体内药代动力学。体外[ 35 S] GTP γ S结合于刺激的GABA测定乙和CB 1点用酒精和巧克力自身给药实验的受体，结合在大鼠中，采用以评估这种新颖的组类似物的药理学特性，使用COR659作为参考化合物。 在肝微粒体温育中发现了COR659的八种代谢物；通过与合成参考标准品比较确定了其中的两个（M1，M2）。M2是噻吩环C-5处甲基的氧化产物，在体外是主
• Heterobicyclic metalloprotease inhibitors
  申请人：Gege Christian

  公开号：US20080261968A1

  公开（公告）日：2008-10-23

  The present invention relates generally to azabicyclic containing pharmaceutical agents, and in particular, to azabicyclic metalloprotease inhibiting compounds. More particularly, the present invention provides a new class of azabicyclic MMP-3, MMP-8 and/or MMP-13 inhibiting compounds, which exhibit an increased potency and selectivity in relation to currently known MMP-13, MMP-8 and MMP-3 inhibitors.

  本发明涉及含有杂环的药物，特别是含有杂环的金属蛋白酶抑制剂。更具体地说，本发明提供了一种新型的杂环MMP-3、MMP-8和/或MMP-13抑制剂，其在与当前已知的MMP-13、MMP-8和MMP-3抑制剂相比具有更高的效力和选择性。
• Discovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of Cyclin D1-CDK4: Synthesis, biological evaluation, and structure–activity relationships
  作者：Takao Horiuchi、Jun Chiba、Kouichi Uoto、Tsunehiko Soga

  DOI：10.1016/j.bmcl.2008.11.090

  日期：2009.1

  The synthesis and evaluation of new analogues of thieno[2,3-d]pyrimidin-4-yl hydrazones are described. 2-Pyrdinecarboxaldehyde [6-(tert-butyl)thieno[2,3-d]pyrimidine-4-yl]hydrazone derivatives have been identified as cyclin-dependent kinase 4 (CDK4) inhibitors. The potency, selectivity pro. le, and structure-activity relationship of this series of compounds are discussed. (C) 2008 Elsevier Ltd. All rights reserved.
• Zhang, Haiqing; Yang, Guichun; Chen, Jianian, Journal of Chemical Research, 2004, # 5, p. 360 - 361
  作者：Zhang, Haiqing、Yang, Guichun、Chen, Jianian、Chen, Zuxing

  DOI：——

  日期：——
• SUGIYAMA, MITSUO;SAKAMOTO, TOSHIAKI;TABATA, KEIICHI;ENDO, KAZUO;ITO, KEII+, CHEM. AND PHARM. BULL., 37,(1987) N, C. 2091-2102
  作者：SUGIYAMA, MITSUO、SAKAMOTO, TOSHIAKI、TABATA, KEIICHI、ENDO, KAZUO、ITO, KEII+

  DOI：——

  日期：——