Chiu-Hong Lin

Synthesis and biological activity of C-5 modified derivatives of (+)-AJ76 and (+)-UH232: Increased dopamine D3 receptor preference and improved pharmacokinetic properties

Abstract A series of (+)-AJ76 and (+)-UH232 analogs with the C-5 methoxy group modified was synthesized and biologically evaluated. Compounds with a triflate or nitrile group were found to be behavioral stimulants with high metabolic stability. The triflate analogs also displayed a 14-fold preference for the D3 receptor site in vitro.

(Dipropylamino)-tetrahydronaphthofurans: centrally acting serotonin agonists and dopamine agonists-antagonists

Abstract CNS-active aminotetralins containing phenolic moieties were transformed in a simple two-step procedure to the corresponding benzofurans. The compounds were tested in in vitro binding studies at serotonin 5-HT1A and 5-HT2 and dopamine D2, D3 and D4 receptors. These studies revealed that the furan homologs showed overall lower affinities than the phenol counterparts. This was also reflected in vivo in biochemical studies. The benzofuran compounds retained most of the agonist/antagonist activities but with lower potency.

Synthesis of isotopically labeled CIS-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-(N-propyl)-1H-benz[e]indole-9-carboxamide, a 5-HT1A receptor agonist

The title compound is a potent and selective 5-HT 1A receptor agonist with clinical potentials for treating anxiety and depression. It has been labeled with stable and radioactive isotopes to support ADME studies in animals and human subjects. Its carboxamide group was labeled with C-14, C-13, or C-13, N-15, and O-18. To provide a radioligand for investigating the receptor binding characteristics of the compound, we also labeled it with tritium in the N-propyl group to obtain the high specific activity of 86.7 Ci/mmol.