Bioorganic & Medicinal ChemistryJanuary 17, 2026Uriel Matthew Enriquez, Natalie M González Velázquez, Mohammad Mosharraf Hossain et al.
Antibodies against small psychoactive molecules have been developed for applications ranging from substance detection and overdose protection to mechanistic understanding of the actions of complex substance mixtures. In this study, we describe the design, synthesis, formulation, and animal testing of an initial immunogenic bioconjugate, as well as subsequent isolation of enantiospecific...
N-Benzyl substitution of phenethylamine 5-HT2A receptor agonists has dramatic effects on binding affinity, receptor selectivity and agonist activity. In this paper we examine how affinity for the 5-HT2A/2C receptors are influenced by N-benzyl substitution of 4-bromo-2,5-dimethoxyphenethylamine derivatives. Special attention is given to the 2' and 3'-position of the N-benzyl as such compounds...
Ajulemic acid, a side-chain analog of Δ(8)-THC-11-oic acid, was designed as a potent therapeutic agent free of the psychotropic adverse effects typical of most cannabinoids. Subsequent studies of ajulemic acid have yielded widely divergent findings on the occurrence of these adverse effects. To help resolve these discrepancies, we have prepared highly purified ajulemic acid using a different...
Modification of the furan ring of salvinorin A (1), the main active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. Conversion of the furan ring to an aldehyde at the C-12 position (5) has allowed for the synthesis of analogues with new carbon-carbon bonds at that position. Previous methods for forming these bonds, such as...
A series of C1, C2, C3 and N6 analogs of nantenine (2) was synthesized and evaluated in 5-HT(2A) and α(1A) receptor functional assays. Alkyl substitution of the C1 and N6 methyl groups of nantenine provided selective 5-HT(2A) and α(1A) antagonists, respectively. The C2 alkyloxy analogs studied were generally selective for α(1A) versus 5-HT(2A). The C3 bromo analog 15 is one of the most potent...
In an effort to find novel agents which selectively target the kappa opioid receptor (KOPR), we modified the furan ring of the highly potent and selective KOPR agonist salvinorin A. Introduction of small substituents at C-16 was well tolerated. 12-epi-Salvinorin A, synthesized in four steps from salvinorin A, was a selective partial agonist at the KOPR. No clear SAR patterns were observed for...
Bioactivity-guided fractionation of the leaves of Salvia divinorum has resulted in the isolation of three new neoclerodane diterpenoids: divinatorin D (1), divinatorin E (2), and salvinorin G (3), together with 10 known terpenoids, divinatorin C (4), hardwickiic acid (5), salvinorin-A (6), -B (7), -C (8), -D (9), -E (10), and -F (11), presqualene alcohol (12), and (E)-phytol (13). The...
Synthesis of 7-heteroaryl-2-azabicyclo[2.2.2]oct-7-enes by cycloaddition and subsequent cross-coupling reaction is described. Binding affinity of these novel compounds towards the characteristic receptorial targets of ibogaine is illustrated.