4-cyano-5-[(2-ethylbutanoyl)amino]-3-methylthiophene-2-carboxylic acid | 691008-14-7

• 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: 4-cyano-5-[(2-ethylbutanoyl)amino]-3-methylthiophene-2-carboxylic acid
• 英文别名: 4-Cyano-5-(2-ethylbutanoylamino)-3-methylthiophene-2-carboxylic acid
• CAS: 691008-14-7
• 化学式: C₁₃H₁₆N₂O₃S
• 分子量: 280.348
• InChiKey: BOZHDNVILIFXOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-cyano-5-[(2-ethylbutanoyl)amino]-3-methylthiophene-2-carboxylic acid 在 甲醇 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 肼 作用下， 以 甲醇 为溶剂， 生成 N-[3-Cyano-5-(hydrazinocarbonyl)-4-methylthien-2-yl]-2-ethylbutanamide
  参考文献：
  名称：

  Discovery and investigation of a novel class of thiophene-derived antagonists of the human glucagon receptor

  摘要：

  A novel class of antagonists of the human glucagon receptor (bGCGR) has been discovered. Systematic modification of the lead compound identified substituents that were essential for activity and those that were amenable to further optimization. This SAR exploration resulted in the synthesis of 13, which exhibited good potency as an hGCGR functional antagonist (IC50 = 34 nM) and moderate bioavailability (36% in mice). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.003
• 作为产物：
  描述：

  2-乙基丁酰氯 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 4-cyano-5-[(2-ethylbutanoyl)amino]-3-methylthiophene-2-carboxylic acid
  参考文献：
  名称：

  Discovery and investigation of a novel class of thiophene-derived antagonists of the human glucagon receptor

  摘要：

  A novel class of antagonists of the human glucagon receptor (bGCGR) has been discovered. Systematic modification of the lead compound identified substituents that were essential for activity and those that were amenable to further optimization. This SAR exploration resulted in the synthesis of 13, which exhibited good potency as an hGCGR functional antagonist (IC50 = 34 nM) and moderate bioavailability (36% in mice). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.003

文献信息

• Cyanothiophene derivatives, compositions containing such compounds and methods of use
  申请人：——

  公开号：US20040097552A1

  公开（公告）日：2004-05-20

  The present invention addresses substituted cyanothiophene derivatives of the formula I: 1 as well as compositions containing such compounds and methods of treatment. The compounds in the present invention are glucagon antagonists. The compounds block the action of glucagon at its receptor and thereby decrease the levels of plasma glucose providing a treatment of diabetes.

  本发明涉及式I的取代氰基噻吩衍生物，以及含有这种化合物的组合物和治疗方法。本发明中的化合物是胰高血糖素拮抗剂。这些化合物阻断了胰高血糖素在其受体上的作用，从而降低血浆葡萄糖水平，提供糖尿病的治疗。
• Direct observation (NMR) of the efficacy of glucagon receptor antagonists in murine liver expressing the human glucagon receptor
  作者：Sheila M. Cohen、Joseph L. Duffy、Corin Miller、Brian A. Kirk、Mari Rios Candelore、Victor D.H. Ding、Gregory Kaczorowski、Laurie M. Tota、Jeffrey G. Werrmann、Michael Wright、Emma R. Parmee、James R. Tata、Bei B. Zhang

  DOI：10.1016/j.bmc.2005.10.008

  日期：2006.3

  The demonstration of pharmacodynamic efficacy of novel chemical entities represents a formidable challenge in the early exploration of synthetic lead classes. Here, we demonstrate a technique to validate the biological efficacy of novel antagonists of the human glucagon receptor (hGCGR) in the surgically removed perfused liver to the optimization of the pharmacokinetic properties of the compounds. The technique involves the direct observation by (CNMR)-C-13 of the biosynthesis of [C-13]glycogen from [13 C]pyruvate via the gluconeogenic pathway. The rapid breakdown of [13C]glycogen (glycogenolysis) following the addition of if 50 pM exogenous glucagon is then monitored in real time in the perfused liver by C-13 NMR. The concentration-dependent inhibition of glucagon-mediated glycogenolysis is demonstrated for both the peptidyl glucagon receptor antagonist 1 and structurally diverse synthetic antagonists 2-7. Perfused livers were obtained from a transgenic mouse strain that exclusively expresses the functional human glucagon receptor, conferring human relevance to the activity observed with glucagon receptor antagonists. This technique does not provide adequate quantitative precision for the comparative ranking of active compounds, but does afford physiological evidence of efficacy in the early development of a chemical series of antagonists. (c) 2005 Elsevier Ltd. All rights reserved.
• US7196106B2
  申请人：——

  公开号：US7196106B2

  公开（公告）日：2007-03-27