Abstract
Provided herein are novel compounds as 5-HT2A agonists, pharmaceutical compositions, use of such compounds in treating mental illness or CNS disorders and processes for preparing such compounds.
Important Compound Classes
Title
Compounds
Patent Publication Number
WO 2026/137050 A1
URL: https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2026137050&_cid=P21-MR76AA-92680-1
Publication Date
July 2, 2026
Priority Application
AU 2024904302
Priority Date
December 24, 2024
Inventors
Banister, S.; Jorgensen, W.; Tan, J.; Whish, L.; Adair, L.
Assignee Company
Psylo Pty Ltd., Australia
Disease Area
Mental Illness and CNS disorders
Biological Target
5-HT2A
Summary
Mental illness covers many neuropsychiatric disorders which cause enormous burden to the lives of their sufferers. Diagnoses such as treatment resistant depression, major depressive disorders, eating disorders, substance abuse disorders, post-traumatic stress disorder, obsessive compulsive disorder, attention deficit disorder, schizophrenia, and others can cause such devastating symptoms that many sufferers lose the capability of leading a normal life.
Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. After the discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD) and the identification of serotonin in the brain, early research focused intensively on LSD. Today, there is consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A (5-HT2A) receptors. Psychedelics have both rapid onset and persisting effects, which includes changes in mood and brain function. The classical psychotic agents include LSD, psilocybin or mescaline.
The 5-HT2A receptor plays an important role in emotional responses and is an important target to be considered in the action of 5-HT2A agonist psychedelics. In fact, a majority of known 5-HT2A agonists produce hallucinogenic effects in humans. Psilocybin activates 5HT1A receptors, which may contribute to antidepressant/antianxiety effects.
Psychosis is often referred to as an abnormal state of mind that is characterized by hallucinatory experiences, delusional thinking and disordered thoughts. Anecdotal evidence suggests that low, nonhallucinogenic doses of psychedelics can reduce symptoms of schizophrenia and psychosis.
The present application describes a series of novel compounds as 5-HT2A agonists for the treatment of mental illness or central nervous system (CNS) disorders. Further, the application discloses compounds, their preparation, use, pharmaceutical composition, and treatment.
Definitions
A = 4–14 membered heterocyclyl substituted with one or more substituents selected from halogen, (O), CN, C1–8 alkoxy, C1–8 alkylamino, C1–8 alkylsulfonyl, COOR4, C(O)N(R4)2, OR4, N(R4)2, NO2, SR4, SO2R4, C1–6 alkyl, C1–6 haloalkyl, C2–6 alkenyl, C2–6 haloalkenyl, C2–6 alkynyl, C2–6 haloalkynyl, C3–6 cycloalkyl, and C3–6 heterocycloalkyl;
R6 = H, C1–6 alkyl, C2–6 alkenyl, C2–6 alkynyl, C1–6 alkyleneP(O)(OR12)2, C(O)R12, COOR12, C(O)N(R12)2, S(O)R12 and SO2R12;
R9 = H, halogen, CN, OR13, N(R13)2, SR13, C1-6 alkyl, C1–6 haloalkyl, C2–6 alkenyl, C2–6 haloalkenyl, C2–6 alkynyl, C2–6 haloalkynyl, C1–6 alkylamine, C1–6 alkoxy, C1–6 haloalkoxy, CO2R13, C(O)R13, C(O)N(R13)2, and C(O)C(O)N(R13)2; and
R10 = H, halogen, CN, OR14, N(R14)2, SR14, C1–6 alkyl, C1–6 haloalkyl, C2–6 alkenyl, C2–6 haloalkenyl, C2–6 alkynyl, C2–6 haloalkynyl, C1–6 alkylamine, C1–6 alkoxy, C1–6 haloalkoxy, CO2R14, C(O)R14, C(O)N(R14)2, and C(O)C(O)N(R14)2.
Key Structures
Biological Assay
The 5-HT2A receptor FLIPR Ca2+ flux functional assay was performed. The compounds described in this application were tested for agonist activity at 5-HT2A receptor. The 5-HT2A EC50 (nM) are shown in the following Table.
Biological Data
Table below shows representative compounds
that were tested for agonist activity at 5-HT2A. The biological data
obtained from testing representative examples are listed in the following
Table.
Claims
Total claims: 22
Compound claims: 18
Pharmaceutical composition claims: 1
Method of treatment claims: 1
Use of compound claims: 1
Medicament claims: 1
Recent Review Articles
See References − .
The authors declare no competing financial interest.
References
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