The cyclopropylmethyl group in classical δ opioid receptor (DOR) antagonist NTI, BNTX, and NTB was replaced with various electron-withdrawing groups to develop DOR inverse agonists. N-Benzyl NTB derivative SYK-657 was a potent DOR full inverse agonist and its potency was over 10-fold potent than that of a reference compound ICI-174,864. Intraperitoneal administration of SYK-657 induced the short-term memory improving effect in mice without abnormal behaviors.
The profound impact of the central metal on the morphological properties of metalloporphyrins bearing 3,4,5-tri((S)-dihydrocitronellyloxy)phenyl groups at the diagonal meso-positions is disclosed. Systematic comparison of the free-base porphyrin 1H 2 with metalloporphyrins 1Ms incorporating Ni(II), Cu(II), and Zn(II) as the central metal found the counterintuitive antifreezing effect of the central metal; 1H 2 crystallizes immediately after the removal of the solvent, while the central metal retards nucleation. We interpret that the miscibility of the elastic alkyl chains and the porphyrin segment is crucial in imparting fluidity to 1M and smooth nucleation in the context of classical nucleation theory, while the full rationalization of the thermal behaviors requires the existence of the nuclei precursor according to the two-step nucleation model. The morphological behaviors of 1Ms are highly susceptible to only marginal differences in the chemical structure, presumably due to the relatively large discrete size of the porphyrin ring, approximately 1 nm. The somewhat counterintuitive antifreezing effect of the central metal is interpreted to arise from the increased viscosity due to the enhanced molecular interactions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.