(1S,4S,10S,13R,18R,21S,24S,27S,30S,38S)-13-[[(2S)-2-amino-1-hydroxy-3-(4-hydroxyphenyl)propylidene]amino]-21-benzyl-38-(3-carbamimidamidopropyl)-3,12,20,23,26,29,36-heptahydroxy-N-[(2S)-1-hydroxy-3-(4-hydroxyphenyl)-1-iminopropan-2-yl]-27-(2-hydroxy-2-iminoethyl)-10-(1H-imidazol-5-ylmethyl)-30-(1H-indol-3-ylmethyl)-24-methyl-9,32-dioxo-15,16,34-trithia-2,8,11,19,22,25,28,31,37-nonazatricyclo[29.4.4.04,8]nonatriaconta-2,11,19,22,25,28,36-heptaene-18-carboximidic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1S,4S,10S,13R,18R,21S,24S,27S,30S,38S)-13-[[(2S)-2-amino-1-hydroxy-3-(4-hydroxyphenyl)propylidene]amino]-21-benzyl-38-(3-carbamimidamidopropyl)-3,12,20,23,26,29,36-heptahydroxy-N-[(2S)-1-hydroxy-3-(4-hydroxyphenyl)-1-iminopropan-2-yl]-27-(2-hydroxy-2-iminoethyl)-10-(1H-imidazol-5-ylmethyl)-30-(1H-indol-3-ylmethyl)-24-methyl-9,32-dioxo-15,16,34-trithia-2,8,11,19,22,25,28,31,37-nonazatricyclo[29.4.4.04,8]nonatriaconta-2,11,19,22,25,28,36-heptaene-18-carboximidic acid
• 化学式: C₇₃H₉₂N₂₀O₁₅S₃
• 分子量: 1585.86
• InChiKey: VEILVGZVAAYSGV-LPUQDNEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  111
• 可旋转键数：
  21
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  640
• 氢给体数：
  18
• 氢受体数：
  21

反应信息

• 作为产物：
  描述：

  以 水 、 二甲基亚砜 为溶剂， 生成 (1S,4S,10S,13R,18R,21S,24S,27S,30S,38S)-13-[[(2S)-2-amino-1-hydroxy-3-(4-hydroxyphenyl)propylidene]amino]-21-benzyl-38-(3-carbamimidamidopropyl)-3,12,20,23,26,29,36-heptahydroxy-N-[(2S)-1-hydroxy-3-(4-hydroxyphenyl)-1-iminopropan-2-yl]-27-(2-hydroxy-2-iminoethyl)-10-(1H-imidazol-5-ylmethyl)-30-(1H-indol-3-ylmethyl)-24-methyl-9,32-dioxo-15,16,34-trithia-2,8,11,19,22,25,28,31,37-nonazatricyclo[29.4.4.04,8]nonatriaconta-2,11,19,22,25,28,36-heptaene-18-carboximidic acid
  参考文献：
  名称：

  Structure–Activity Relationships of Peptides Incorporating a Bioactive Reverse-Turn Heterocycle at the Melanocortin Receptors: Identification of a 5800-fold Mouse Melanocortin-3 Receptor (mMC3R) Selective Antagonist/Partial Agonist versus the Mouse Melanocortin-4 Receptor (mMC4R)

  摘要：

  The melanocortin-3 (MC3) and melanocortin-4 (MC4) receptors regulate energy homeostasis, food intake, and associated physiological conditions. The melanocortin-4 receptor (MC4R) has been studied extensively. Less is known about specific physiological roles of the melanocortin-3 receptor (MC3R). A major obstacle to this lack of knowledge is attributed to a limited number of identified MC3R selective ligands. We previously reported a spatial scanning approach of a 10-membered thioether-heterocycle ring incorporated into a chimeric peptide template that identified a lead nM MC4R ligand. Upon the basis of those results, 17 compounds were designed and synthesized that focused upon modification in the pharmacophore domain. Notable results include the identification of a 0.13 nM potent 5800-fold mMC3R selective antagonist/slight partial agonist versus a 760 nM mMC4R full agonist (ligand 11). Biophysical experiments (two-dimensional H-1 NMR and computer-assisted molecular modeling) of this ligand resulted in the identification of an inverse gamma-turn secondary structure in the ligand pharmacophore domain.

  DOI：

  10.1021/jm301253y