Dmt-c(SCH₂CH₂S)[DCys-Aci-DPen]OH | 1343346-03-1

• 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: Dmt-c(SCH₂CH₂S)[DCys-Aci-DPen]OH
• 英文别名: 2',6'-dimethyltyrosine-c(SCH₂CH₂S)[DCys-(2-aminoindane-2-carboxylic acid)-D-penicillamine]OH；(6'S,12'S)-12'-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-5',5'-dimethyl-8',11'-dioxospiro[1,3-dihydroindene-2,9'-1,4-dithia-7,10-diazacyclotridecane]-6'-carboxylic acid
• CAS: 1343346-03-1
• 化学式: C₃₁H₄₀N₄O₆S₂
• 分子量: 628.814
• InChiKey: UGKRKUQKVQDHJB-GVAUOCQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  43
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  221
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  、 1,2-二溴乙烷 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 Dmt-c(SCH₂CH₂S)[DCys-Aci-DPen]OH
  参考文献：
  名称：

  Development and in Vitro Characterization of a Novel Bifunctional μ-Agonist/δ-Antagonist Opioid Tetrapeptide

  摘要：

  The development of tolerance to and dependence on opioid analgesics greatly reduces their long-term usefulness. Previous studies have demonstrated that co-administration of a mu-opioid receptor (MOB.) agonist and delta-opioid receptor (DOR) antagonist can decrease MOR agonist-induced, tolerance and dependence development after chronic exposure. Clinically, a single ligand displaying multiple efficacies (e.g., MOR agonism concurrently with DOR antagonism) would be of increased value over two drugs administered simultaneously. Guided by modeling of receptor-ligand complexes we have developed a series of potent non-selective opioid tetrapeptides that have differing efficacy at MOR and DOR In particular, our lead peptide (KSK-103) binds with equal affinity to MOR and DOR but acts as a MOR agonist with similar efficacy but greater potency than morphine and a DOR antagonist in cellular assays measuring both G protein stimulation and adenylyl cyclase inhibition.

  DOI：

  10.1021/cb200263q

文献信息

• COMPOUND AND METHOD FOR MODULATING OPIOID RECEPTOR ACTIVITY
  申请人：The Regents of The University of Michigan

  公开号：EP2723761B1

  公开（公告）日：2017-11-08
• US9045526B2
  申请人：——

  公开号：US9045526B2

  公开（公告）日：2015-06-02
• [EN] COMPOUND AND METHOD FOR MODULATING OPIOID RECEPTOR ACTIVITY<br/>[FR] COMPOSÉ ET PROCÉDÉ POUR MODULATION D'ACTIVITÉ DE RÉCEPTEUR DES OPIOÏDES
  申请人：UNIV MICHIGAN

  公开号：WO2012178063A1

  公开（公告）日：2012-12-27

  The invention provides a compound of formula (I), wherein R1 is H, C(NH)NH2, an amino acid, or a peptide; X is OH, NH2, NHR2, NR 2R 3, an amino acid, or a peptide; R 2 and R 3 are selected from alkyl, alkylenearyl, or alkyleneheteroaryl; each R4 and R5 is independently H or CH3; Z is 2-amino-2,3-dihydro-lH- indene-2-carboxylic acid; 2-amino-l,2,3,4-tetrahydronaphthalene-2-carboxylic acid; 6- amino-6,7,8,9-tetrahydro-5H-benzo[7]annulene 6-carboxylic acid; cyclohexylalanine; cyclohexylglycine; homophenylalanine; 1-naphthylalanine; 2-naphthylalanine; 1,2,3,4- tetrahydroisoquinoline-3-carboxylic acid; or octahydro-lH-indole-2-carboxylic acid; n is 0, 1, 2, 3, or 4; with the proviso that X is not NH2 when R1 is H, R4 is H, R5 is CH3, Z is Aci, and n is 2; or a pharmaceutically acceptable salt, ester or solvate thereof. A method of treating pain and a method for treating a mu-opioid receptor mediated disorder and/or a delta-opioid receptor mediated disorder also are provided.