928232-30-8

Upstream product

• 99953-00-1 (S)-N-Boc-2,6-dimethyltyrosine 
• 147-85-3 L-proline 

Downstream Products

• 943726-86-1 N^α-tert-butyloxycarbonyl-2',6'-methyl-L-tyrosyl-L-prolyl-2'-ethyl-6'-methyl-L-phenylalanyl-L-phenylalanylamide 
• 943726-77-0 N^α-tert-butyloxycarbonyl-2',6'-dimethyl-L-tyrosyl-L-prolyl-2'-methyl-L-phenylalanyl-L-phenylalanylamide 
• 943726-79-2 N^α-tert-butyloxycarbonyl-2',6'-dimethyl-L-tyrosyl-L-prolyl-3',5'-dimethyl-L-phenylalanyl-L-phenylalanylamide 
• 943726-80-5 N^α-tert-butyloxycarbonyl-2',6'-dimethyl-L-tyrosyl-L-prolyl-2',6'-dimethyl-L-phenylalanyl-L-phenylalanylamide 
• 943726-82-7 N^α-tert-butyloxycarbonyl-2',6'-dimethyl-L-tyrosyl-L-prolyl-2',6'-dimethyl-L-tyrosyl-L-phenylalanylamide 
• 943726-84-9 N^α-tert-butyloxycarbonyl-2',6'-dimethyl-L-tyrosyl-L-prolyl-2',4',6'-trimethyl-L-phenylalanyl-L-phenylalanylamide 
• 943726-88-3 N^α-tert-butyloxycarbonyl-2',6'-dimethyl-L-tyrosyl-L-prolyl-2'-isopropyl-6'-methyl-L-phenylalanyl-L-phenylalanylamide 

Relevant academic research and scientific papers

Endomorphin-1 analogs containing α-methyl-β-Amino acids exhibit potent analgesic activity after peripheral administration

This study describes the design and synthesis of endomorphin-1 analogs containing C-Terminal aromatic α-methyl-β-Amino acids and an N-Terminal native tyrosine or 2,6-dimethyl-Tyrosine. We show that, in comparison with the parent peptide, these analogs exhibit improved bioactivity and blood-brain barrier penetration after intravenous administration, and have a lower tendency to induce constipation and sedation than morphine.

Transformation of μ-opioid receptor agonists into biologically potent μ-opioid receptor antagonists

N-Allylation (-CH2-CH{double bond, long}CH2) of [Dmt1]endomorphins yielded the following: (i) [N-allyl-Dmt1]endomorphin-2 (Dmt = 2′,6′-dimethyl-l-tyrosine) (12) and [N-allyl-Dmt1]endomorphin-1 (15) (Kiμ = 0.45 and 0.26 nM, respectively) became μ-antagonists (pA2 = 8.59 and 8.18, respectively) with weak δ-antagonism (pA2 = 6.32 and 7.32, respectively); (ii) intracerebroventricularly administered 12 inhibited morphine-induced CNS-mediated antinociception in mice [AD50 (0.148 ng/mouse) was 16-fold more potent than naloxone], but not spinal antinociception, and (iii) 15 reversed the alcohol-elevated frequency in spontaneous inhibitory post-synaptic currents (IPSC) in hippocampal CA1 pyramidal cells in rat brain slices (P = 0.0055). Similarly, N-allylation of the potent μ-opioidmimetic agonists, 1,6-bis-[H-Dmt-NH]-hexane and 3,6-bis-[Dmt-NH-propyl]-2(1H)-pyrazinone, converted them into μ-antagonists (pA2 = 7.23 and 7.17 for the N-allyl-derivatives 17 and 19, respectively), and exhibited weak δ-antagonism. Thus, N-allylation of Dmt containing opioid peptides or opioidmimetics continues to provide a facile means to convert selective μ-opioid agonists into potent μ-opioid antagonists.