SC4 | 1364692-88-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: SC4
• 英文别名: 5-{[6-chloro-5-(2'-hydroxy[1,1'-biphenyl]-4-yl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy}-2-methylbenzoic acid；5-[[6-chloro-5-[4-(2-hydroxyphenyl)phenyl]-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2-methylbenzoic acid
• CAS: 1364692-88-5
• 化学式: C₂₆H₁₈ClN₃O₄
• 分子量: 471.9
• InChiKey: MEZQZPGDJJEQPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-羟基-2-甲基苯甲酸甲酯 在 bis-triphenylphosphine-palladium(II) chloride 、 四丁基氟化铵 、 potassium carbonate 、 caesium carbonate 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.75h， 生成 SC4
  参考文献：
  名称：

  Structural Determinants for Small-Molecule Activation of Skeletal Muscle AMPK α2β2γ1 by the Glucose Importagog SC4

  摘要：

  The AMP-activated protein kinase (AMPK) alpha beta gamma het-erotrimer regulates cellular energy homeostasis with tissue-specific isoform distribution. Smallmolecule activation of skeletal muscle alpha 2 beta 2 AMPK complexes may prove a valuable treatment strategy for type 2 diabetes and insulin resistance. Herein, we report the small-molecule SC4 is a potent, direct AMPK activator that preferentially activates alpha 2 complexes and stimulates skeletal muscle glucose uptake. In parallel with the term secretagog, we propose "importagog" to define a substance that induces or augments cellular uptake of another substance. Three-dimensional structures of the glucose importagog SC4 bound to activated alpha 2 beta 2 gamma 1 and alpha 2 beta 1 gamma 1 complexes reveal binding determinants, in particular a key interaction between the SC4 imidazopyridine 4'-nitrogen and beta 2-Asp111, which provide a design paradigm for beta 2-AMPK therapeutics. The alpha 2 beta 2 gamma 1/SC4 structure reveals an interaction between a beta 2 N-terminal alpha helix and the alpha 2 autoinhibitory domain. Our results provide a structurefunction guide to accelerate development of potent, but importantly tissue-specific, beta 2-AMPK therapeutics.

  DOI：

  10.1016/j.chembiol.2018.03.008

文献信息

• HETERO RING-FUSED IMIDAZOLE DERIVATIVE HAVING AMPK ACTIVATING EFFECT
  申请人：Tonogaki Keisuke

  公开号：US20130184240A1

  公开（公告）日：2013-07-18

  Disclosed is a compound which is useful as an AMPK activator. A compound represented by the formula: its pharmaceutically acceptable salt, or a solvate thereof, wherein a group represented by the formula: is a group represented by the formula: R 1 is each independently halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or the like; m is an integer of 0 to 3; R 2 is hydrogen, or substituted or unsubstituted alkyl; X is —O—; and Y is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

  揭示了一种作为AMPK激活剂有用的化合物。一种由以下公式表示的化合物：其药学上可接受的盐，或其溶剂化合物，其中由以下公式表示的基团：是由以下公式表示的基团：R1是各自独立的卤素、羟基、氰基、硝基、羧基、取代或未取代的烷基、取代或未取代的烯烃基或类似物；m是0到3的整数；R2是氢，或取代或未取代的烷基；X是—O—；Y是取代或未取代的芳基，或取代或未取代的杂环芳基。
• US9133186B2
  申请人：——

  公开号：US9133186B2

  公开（公告）日：2015-09-15
• Structural Determinants for Small-Molecule Activation of Skeletal Muscle AMPK α2β2γ1 by the Glucose Importagog SC4
  作者：Kevin R.W. Ngoei、Christopher G. Langendorf、Naomi X.Y. Ling、Ashfaqul Hoque、Swapna Varghese、Michelle A. Camerino、Scott R. Walker、Ylva E. Bozikis、Toby A. Dite、Ashley J. Ovens、William J. Smiles、Roxane Jacobs、He Huang、Michael W. Parker、John W. Scott、Mark H. Rider、Richard C. Foitzik、Bruce E. Kemp、Jonathan B. Baell、Jonathan S. Oakhill

  DOI：10.1016/j.chembiol.2018.03.008

  日期：2018.6

  The AMP-activated protein kinase (AMPK) alpha beta gamma het-erotrimer regulates cellular energy homeostasis with tissue-specific isoform distribution. Smallmolecule activation of skeletal muscle alpha 2 beta 2 AMPK complexes may prove a valuable treatment strategy for type 2 diabetes and insulin resistance. Herein, we report the small-molecule SC4 is a potent, direct AMPK activator that preferentially activates alpha 2 complexes and stimulates skeletal muscle glucose uptake. In parallel with the term secretagog, we propose "importagog" to define a substance that induces or augments cellular uptake of another substance. Three-dimensional structures of the glucose importagog SC4 bound to activated alpha 2 beta 2 gamma 1 and alpha 2 beta 1 gamma 1 complexes reveal binding determinants, in particular a key interaction between the SC4 imidazopyridine 4'-nitrogen and beta 2-Asp111, which provide a design paradigm for beta 2-AMPK therapeutics. The alpha 2 beta 2 gamma 1/SC4 structure reveals an interaction between a beta 2 N-terminal alpha helix and the alpha 2 autoinhibitory domain. Our results provide a structurefunction guide to accelerate development of potent, but importantly tissue-specific, beta 2-AMPK therapeutics.