Classics in Chemical Neuroscience: Pramipexole.

Pramipexole was first manufactured by Pharmacia and Upjohn in July 1997 under the United States brand names of Mirapex and Mirapex ER. Pramipexole is classified as a nonergoline aminobenzothiazole compound that selectively agonizes the dopamine D2-like receptor subfamily, which includes the D2, D3, and D4 receptor subtypes. Pramipexole is a unique compound in its therapeutic potential because it has D3-preferring properties. The D3 receptor target has implications in both motor and psychiatric symptoms of Parkinson's disease, restless leg syndrome, and bipolar and unipolar depression. Currently, pramipexole is approved to treat signs and symptoms of idiopathic Parkinson's disease and moderate to severe symptoms of primary restless leg syndrome. Parkinson's disease is characterized by tremor, bradykinesia, rigidity, gait disorders, and a disturbance of posture due to a decrease in dopamine stores in the substantia nigra with the consequent presence of Lewy bodies. Restless leg syndrome is a neurologic sensorimotor disorder characterized by a compelling urge to move the body/limb to relieve this uncomfortable sensation. In this Review, we will discuss the synthesis, drug metabolism, pharmacology, adverse effects, history, and the importance of pramipexole to neuroscience and describe its role in therapy.

Highly Stereoselective Synthesis of Terminal Chloro-Substituted Propargylamines and Further Functionalization.

The highly stereoselective addition of lithiated chloroacetylene, derived in situ from cis-1,2-dichloroethene and methyl lithium, to Ellman chiral N-tert-butanesulfinyl imines is reported. The reaction proceeds in high yield (up to 98%) and with excellent diastereoselectivity (up to >20:1) for a variety of aryl, heteroaromatic, alkyl, and α,ß-unsaturated imine substrates. Transformations of the terminal chloro-substituted propargylamine products are described in which lithium-halogen exchange yields nucleophilic acetylides that can be quenched to yield terminal alkynes or intercepted by carbon electrophiles.