403652-18-6

Upstream product

• 115962-35-1 (3S)-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinole-3-carboxylic acid 

Relevant academic research and scientific papers

Synthesis and opioid activity of N,N-Dimethyl-Dmt-Tic-NH-CH(R)-R′ analogues: Acquisition of potent δ antagonism

N,N-Dimethylation of the H-Dmt-Tic-NH-CH(R)-R′ series of compounds produced no significant affect on the high δ-opioid receptor affinity (Ki=0.035-0.454 nM), but dramatically decreased that for the μ-opioid receptor. The effect of N-methylation was independent of the length of the linker (R); however, the bioactivities were affected by the chemical composition of the third aromatic group (R′): phenyl (Ph) (5′-8′) elicited a greater reduction in μ-affinity (40-70-fold) compared to analogues containing 1H-benzimidazole-2-yl (Bid) (9-fold). The major consequences of N,N-dimethylation on in vitro bioactivity were: (i) a loss of δ-agonism coupled with the appearance of potent δ antagonism (4′-7′) (pA2=8.14-9.47), while 1 exhibited only a 160-fold decreased δ agonism (1′) and the δ antagonism of 8 enhanced >10-fold (pA2=10.62, 8′); and (ii) a consistent loss of μ-affinity resulted in enhanced δ-opioid receptor selectivity. With the exception of compound 1′, the change in the hydrophobic environment at the N-terminus and formation of a tertiary amine by N,N-dimethylation in analogues of the Dmt-Tic pharmacophore produced potent δ-selective antagonists.

Evaluation of the Dmt-Tic pharmacophore: Conversion of a potent δ-opioid receptor antagonist into a potent δ agonist and ligands with mixed properties

Analogues of the 2′,6′-dimethyl-L-tyrosine (Dmt)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) pharmacophore were prepared to test the hypothesis that a "spacer" and a third aromatic center in opioid peptides are required to convert a δ-antagonis