(2S,5S,8S,11S,14R,19R,22S,25R,28S,34S)-N-[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-19-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-5-(2-amino-2-oxoethyl)-11,25-dibenzyl-34-[3-(diaminomethylideneamino)propyl]-22-(1H-imidazol-5-ylmethyl)-8-methyl-2-(naphthalen-2-ylmethyl)-3,6,9,12,20,23,26,32,36-nonaoxo-16,17,30-trithia-1,4,7,10,13,21,24,27,35-nonazabicyclo[26.4.4]hexatriacontane-14-carboxamide

• 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: (2S,5S,8S,11S,14R,19R,22S,25R,28S,34S)-N-[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-19-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-5-(2-amino-2-oxoethyl)-11,25-dibenzyl-34-[3-(diaminomethylideneamino)propyl]-22-(1H-imidazol-5-ylmethyl)-8-methyl-2-(naphthalen-2-ylmethyl)-3,6,9,12,20,23,26,32,36-nonaoxo-16,17,30-trithia-1,4,7,10,13,21,24,27,35-nonazabicyclo[26.4.4]hexatriacontane-14-carboxamide
• 化学式: C₇₉H₉₅N₁₉O₁₅S₃
• 分子量: 1646.94
• InChiKey: KIRVLPVFDKQTQF-QLFNPVIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  116
• 可旋转键数：
  23
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  633
• 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 (2S,5S,8S,11S,14R,19R,22S,25R,28S,34S)-N-[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-19-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-5-(2-amino-2-oxoethyl)-11,25-dibenzyl-34-[3-(diaminomethylideneamino)propyl]-22-(1H-imidazol-5-ylmethyl)-8-methyl-2-(naphthalen-2-ylmethyl)-3,6,9,12,20,23,26,32,36-nonaoxo-16,17,30-trithia-1,4,7,10,13,21,24,27,35-nonazabicyclo[26.4.4]hexatriacontane-14-carboxamide
  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

文献信息

• 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)
  作者：Anamika Singh、Marvin Dirain、Rachel Witek、James R. Rocca、Arthur S. Edison、Carrie Haskell-Luevano

  DOI：10.1021/jm301253y

  日期：2013.4.11

  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.