An Immunconjugate Vaccine Alters Distribution and Reduces the Antinociceptive, Behavioral and Physiological Effects of Fentanyl in Male and Female Rats.

Fentanyl (FEN) is a potent synthetic opioid associated with increasing incidence of opioid use disorder (OUD) and fatal opioid overdose. Vaccine immunotherapy for FEN-associated disorders may be a viable therapeutic strategy. Here, we expand and confirm our previous study in mice showing immunological and antinociception efficacy of our FEN vaccine administered with the adjuvant dmLT.

Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge.

Fentanyl is a major contributor to the devastating increase in overdose deaths from substance use disorders (SUD). A vaccine targeting fentanyl could be a powerful immunotherapeutic. Here, we evaluated adjuvant and delivery strategies for conjugate antigen vaccination with fentanyl-based haptens.

Hypervalent Iodine Mediated Oxidative Cyclization of Acrylamide -Carbamates to 5,5-Disubstituted Oxazolidine-2,4-diones.

A metal-free oxidative cyclization of -Boc-acrylamides with (diacetoxyiodo)benzene in acetic acid produced 5,5-disubstituted oxazolidine-2,4-diones with the formation of a C-O bond in moderate to excellent yields. In addition, the reaction was diastereospecific with -Boc-2,3-dimethylacrylamides and proceeded with phenyl migration in the case of an -Boc-2-phenylacrylamide to generate a 5-acetoxy-5-benzyloxazolidine-2,4-dione.

Pyrimidinyl Biphenylureas: Identification of New Lead Compounds as Allosteric Modulators of the Cannabinoid Receptor CB.

The allosteric modulator 1-(4-chlorophenyl)-3-(3-(6-(pyrrolidin-1-yl)pyridin-2-yl)phenyl)urea (PSNCBAM-1, 2) bound the cannabinoid receptor 1 (CB) and antagonized G protein coupling. This compound demonstrated potent anorectic effects similar to the CB antagonist rimonabant that once was marketed for the treatment of obesity, suggesting a new chemical entity for the discovery of antiobesity drugs. To increase structural diversity of this class of CB ligands, we designed and synthesized two classes of novel analogues, in which the pyridine ring of 2 was replaced by a pyrimidine ring.