Potent dihydroquinolinone dopamine D2 partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia

Update 1 of: Recent Progress in Development of Dopamine Receptor Subtype-Selective Agents: Potential Therapeutics for Neurological and Psychiatric Disorders

“…Compounds 239 and 240 represent a series of dihydroquinolinone analogs bearing a conformationally constrained linker. These compounds also displayed high binding affinity at the same two sites (D 2 K i = 11 and 16 nM; SERT K i = 1.7 and 0.26 nM), and the sulfonamide 239 was almost inactive at α 1 adrenergic receptors …”

“…These compounds also displayed high binding affinity at the same two sites (D 2 K i = 11 and 16 nM; SERT K i = 1.7 and 0.26 nM), and the sulfonamide 239 was almost inactive at α 1 adrenergic receptors. 217 3.2.4.3. Heteroarylpiperidines with Mixed D 2 and α 1 Receptor Antagonist Activities.…”

Iron‐Catalyzed Intramolecular Arene C(sp2)−H Amidations under Mechanochemical Conditions

“…al motifs occurring in natural products, [1] biologically active compounds, [2] and drugs. [3] Over the past decades, various synthetic approaches towards 3,4-dihydro-2(1H)-quinolinones have been developed, including Friedel-Crafts alkylations, [4] transition metal catalyses, [5] and radical reactions. [6] Although these methods can be efficient in given synthetic settings, they commonly require prefunctionalized substrates resulting from multi-step syntheses or involve complex reaction conditions, which limits their applicability.…”

Synthesis of Tripeptide Mimetics Based on Dihydroquinolinone and Benzoxazinone Scaffolds

“…[6] The dihydroquinolinone motif is rarely found in nature, [7] but is present in the core of commercial drugs, such as cilostazol, [8] aripiprazole [9] and carteolol. [10] Over the years, both dihydroquinolinone [8][9][10][11] and benzoxazinone [6,12] heterocycles have been intensively exploited in the development of new drug leads. Potential therapeutic applications of these templates are very broad, including their use as analgesic, antidepressant, antipsychotic, vasodilator, antifungal and anticonvulsant agents.…”

“…[14] Here, we describe the synthesis of the dihydroquinoline 2 and benzoxaninone 3 peptidomimetics. Although the synthesis of many molecules containing the heterobicycle skeleton has been reported, [11,15,16] the particular substitution pattern found in molecules 2 and 3 (in which the À OH and À NH 2 groups are in meta position to the NH moiety of the heterocycle) is novel and, in the case of 2, imposes an unprecedented synthesis challenge. The key strategy to furnish these compounds is the regioselective incorporation of nitro groups at the phenol precursor prior to reductive ring closing lactamisation.…”