1384967-96-7

Upstream product

• 1346683-43-9 dimethyl (2-oxo-2-(1H-pyrrol-1-yl)ethyl)phosphonate 
• 155396-71-7 tert-butyl N-(phenyl(phenylsulfonyl)methyl)carbamate 
• 54582-33-1 1,1'-carbonyldiimidazole 

Downstream Products

• 1186668-56-3 methyl (S)-2-{[(tert-butoxycarbonyl)amino](phenyl)methyl}acrylate 
• 1402733-03-2 C₂₅H₂₉N₃O₄ 
• 1402733-11-2 C₃₉H₄₅N₅O₇ 
• 1402732-84-6 C₂₄H₂₉N₃O₄ 
• 1402732-96-0 C₃₈H₄₅N₅O₇ 
• 1385032-37-0 C₃₃H₃₇N₅O₅ 
• 1385032-38-1 C₃₄H₃₇N₅O₅ 
• 186371-25-5 (S)-2-(((tert-butoxycarbonyl)amino)(phenyl)methyl)acrylic acid 
• 1427063-22-6 C₄₀H₄₆N₆O₇ 
• 1427063-20-4 C₄₀H₄₆N₆O₇ 
• 1427063-06-6 C₃₅H₃₈N₆O₅ 
• 1427063-04-4 C₃₅H₃₈N₆O₅ 

Relevant academic research and scientific papers

Design, synthesis, and pharmacological characterization of novel endomorphin-1 analogues as extremely potent μ-opioid agonists

Recently we reported the synthesis and structure-activity study of endomorphin-1 (EM-1) analogues containing novel, unnatural α-methylene- β-aminopropanoic acids (Map). In the present study, we describe new EM-1 analogues containing Dmt1, (R/S)-βPro2, and (ph)Map4/(2-furyl)Map4. All of the analogues showed a high affinity for the μ-opioid receptor (MOR) and increased stability in mouse brain homogenates. Of the new compounds, Dmt1-(R)-βPro 2-Trp3-(2-furyl)Map4 (analogue 12) displayed the highest affinity toward MOR, in the picomolar range (Ki μ = 3.72 pM). Forskolin-induced cAMP accumulation assays indicated that this analogue displayed an extremely high agonistic potency, in the subpicomolar range (EC50 = 0.0421 pM, Emax = 99.5%). This compound also displayed stronger in vivo antinociceptive activity after iv administration when compared to morphine in the tail-flick test, which indicates that this analogue was able to cross the blood-brain barrier.

A new class of highly potent and selective endomorphin-1 analogues containing α-methylene-β-aminopropanoic acids (map)

A new class of endomorphin-1 (EM-1) analogues were synthesized by introduction of novel unnatural α-methylene-β-amino acids (Map) at position 3 or/and position 4. Their binding and functional activity, metabolic stability, and antinociceptive activity were determined and compared. Most of these analogues showed high affinities for the μ-opioid receptor and an increased stability in mouse brain homogenates compared with EM-1. Examination of cAMP accumulation and ERK1/2 phosphorylation in HEK293 cells confirmed the agonist properties of these analogues. Among these new analogues, H-Tyr-Pro-Trp-(2-furyl)Map-NH2 (analogue 12) exhibited the highest binding potency (Kiμ = 0.221 nM) and efficacy (EC 50 = 0.0334 nM, Emax = 97.14%). This analogue also displayed enhanced antinociceptive activity in vivo in comparison to EM-1. Molecular modeling approaches were then carried out to demonstrate the interaction pattern of these analogues with the opioid receptors. We found that, compared to EM-1, the incorporation of our synthesized Map at position 4 would bring the analogue to a closer binding mode with the μ-opioid receptor.