The Non-Anhydrous, Minimally Basic Synthesis of the Dopamine D Agonist [18F]MCL-524.

The dopamine D agonist MCL-524 is selective for the D receptor in the high-affinity state (D), and, therefore, the PET analogue, [F]MCL-524, may facilitate the elucidation of the role of D in disorders such as schizophrenia. However, the previously reported synthesis of [F]MCL-524 proved difficult to replicate and was lacking experimental details. We therefore developed a new synthesis of [F]MCL-524 using a "non-anhydrous, minimally basic" (NAMB) approach.

The High Affinity Dopamine D Receptor Agonist MCL-536: A New Tool for Studying Dopaminergic Contribution to Neurological Disorders.

The dopamine D receptor exists in two different states, D and D; the former is the functional form of the D receptor and associates with intracellular G-proteins. The D agonist [H]MCL-536 has high affinity for the D receptor ( 0.8 nM) and potently displaces the binding of (-(-)---propylnorapomorphine (NPA; 0.

A non-anhydrous, minimally basic protocol for the simplification of nucleophilic F-fluorination chemistry.

Fluorine-18 radiolabeling typically includes several conserved steps including elution of the [F]fluoride from an anion exchange cartridge with a basic solution of KCO or KHCO and Kryptofix 2.2.2.

Identification of fluorinated (R)-(-)-aporphine derivatives as potent and selective ligands at serotonin 5-HT receptor.

A series of novel aporphine derivatives were synthesized for initial screening at the 5-HT receptor subtypes. Among them, Compounds 11a and 11b were identified as potent 5-HT hit ligands with high selectivity over other 5-HT receptor subtypes. Molecular docking study revealed that compounds 11a and 11b formed two key interactions with the binding site of 5-HT receptor, including a salt-bridge to D3.

New Dopamine D2 Receptor Agonist, [H]MCL-536, for Detecting Dopamine D2high Receptors in Vivo.

Increases in the D2 receptor high affinity state are associated with certain neurological disorders. We synthesized and characterized the high-affinity D2high ligand [H]MCL-536 in competition binding against the D2/3 agonist R-(-)- N- n-propylnorapomorphine (NPA) and the D2/3 antagonist raclopride. The total binding of [H]MCL-536 (minus that in the presence of 100 nM NPA) was measured by saturation binding in CHO cells expressing human D2long; the data yielded separable, nonsaturable nonspecific, and saturable specific components.