title: The Isoxazole Ring and Its N-Oxide: A Privileged Core Structure in Neuropsychiatric Therapeutics.
abstract: Mental disorders are neuropsychiatric conditions that are marked by unusual or irregular thinking, feelings, or behavior, and lead to distress and/or impaired functions. Major psychiatric conditions are depression, anxiety, and psychoses of various types. Their etiopathogeneses, of a primary or secondary origin, are associated with genetic and environmental factors. They are commonly treated with psychoactive drugs (also known as psychotropics), which target serotonin, dopamine, norepinephrine, glutamate, and nuclear receptors (NRs), including retinoic acid receptor-related orphan receptors (RORs) and other receptors in the central nervous system (CNS). Herein we present a diverse array of isoxazole derivatives, among which are some prominent marketed drugs. Some of the derivatives and forms, including N-oxides, are under either (pre)clinical evaluation or patent protection as new generation of psychotropics, and a few have effective blood-brain barrier (BBB) permeability. Various drug-like isoxazol(in)es and their structural features and efficiency, modified through scaffold hopping, are described and discussed in the context of treating neuropsychiatric conditions.
authors.affiliation: Laboratory of Medicinal Chemistry, Department of Pharmacy, University of Patras, 265 04, Patras, Greece.
authors.forename: George N
authors.identifier: 0000-0001-6499-8648
authors.initials: GN
authors.lastname: Pairas
authors.affiliation: Laboratory of Enzyme Technology, Department of Biotechnology, Agricultural University of Athens, 75 Iera Odos St., 118 55, Athens, Greece.
authors.forename: Fereniki
authors.initials: F
authors.lastname: Perperopoulou
authors.affiliation: Laboratory of Biochemistry, Hellenic Pasteur Institute, 127 Vas. Sofias Ave., 115 21, Athens, Greece.
authors.forename: Petros G
authors.identifier: 0000-0002-4256-896X
authors.initials: PG
authors.lastname: Tsoungas
authors.affiliation: Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 451 10, Ioannina, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Varvounis
mesh_terms: D001812:Blood-Brain Barrier / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry*; D001523:Mental Disorders / Q000188:drug therapy; D009584:Nitrogen / Q000737:chemistry; D010087:Oxides / Q000737:chemistry*; D011619:Psychotropic Drugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D007555:Isoxazoles; D010087:Oxides; D011619:Psychotropic Drugs; D018160:Receptors, Cytoplasmic and Nuclear; D009584:Nitrogen
keywords: drug design; isoxazoles; isoxazolines; neurotherapeutics; psychotropics