(S)-(−)-4-[4-[2-(Isochroman-1-yl)ethyl]piperazin-1-yl]benzenesulfonamide, a Selective Dopamine D₄ Antagonist

Abstract

Schizophrenia affects about 1% of the population worldwide. 1 The onset of symptoms is generally in the late teens to early twenties. There is no cure for the disease, and current therapies have numerous, debilitating side effects. The combination of early onset of chronic disease and problematic therapies results in high costs for the patient, his or her family, and society at large. 2 While the etiology of schizophrenia remains unknown, several lines of research point to the dopaminergic system, 3 and, in particular, the dopamine D 4 receptor, as important in schizophrenia and psychotictype diseases in general. 4 Classical antipsychotics such as haloperidol, though effective in treating certain schizophrenic states, cause extrapyramidal side effects and tardive dyskinesias. These side effects have been linked to the blockade of dopamine receptors in the striatum. 5 Clozapine (1), an "atypical" antipsychotic, is relatively free of extrapyramidal side effects, but causes tachycardia (25%), sialorrhea (30%), dizziness (20%), drowsiness and sedation (40%), and agranulocytosis (1-3%). Many of these side effects can be attributed to clozapine's high affinity for a number of central nervous system (CNS) receptors. 6 At the same time, clozapine's affinity for the D 4 receptor may play a part in its atypical nature.

Enantioselective Allylic C−H Oxidation of Terminal Olefins to Isochromans by Palladium(II)/Chiral Sulfoxide Catalysis

“…11 is a precursor to ( S )-Sonepiprazole ( 12 ), whose synthesis via asymmetric C–H oxidation proceeds with a higher overall yield than the reported synthesis via kinetic resolution. [23] …”

Enantioselective Allylic C−H Oxidation of Terminal Olefins to Isochromans by Palladium(II)/Chiral Sulfoxide Catalysis

“…Importantly, all of these manipulations proceeded without racemization of the stereocenter. The compound 11 is a precursor to ( S )‐Sonepiprazole ( 12 ), whose synthesis by asymmetric C−H oxidation proceeds with a higher overall yield than the reported synthesis by kinetic resolution …”

WAY 100635 produces discriminative stimulus effects in rats mediated by dopamine D4 receptor activation

“…The training drug: WAY 100635 (Forster et al, 1995), (Nakane et al, 2005), and sonepiprazole (U-101387, PNU1012387G; (-)-4-[4-[2-(3,4-dihydro-1H-2-benzopyran-1-yl)ethyl]-1-piper azinyl]-benzenesulfonamide monomethanesulfonate) (Tenbrink et al, 1996) were synthesized in our laboratory. 8-OH-DPAT and (-)-pindolol were purchased from TOCRIS (Ellisville, Missouri, USA).…”