Substituted pyrazolopyrimidinone compounds as PDE2 inhibitors
Inventors
Gomez, Laurent • Vernier, William Francois
Assignees
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Publication Number
US-12715875-B2
Publication Date
2026-08-25
Expiration Date
Abstract
A chemical entity of Formula (I): wherein V, W, Y, and Z, have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies; detection and imaging techniques; radioactive treatments; modulating and treating disorders mediated by PDE2 activity; treating neurological disorders, CNS disorders, dementia, cognitive disorders, neurodegenerative diseases, and trauma-dependent losses of function; enhancing the efficiency of cognitive and motor training, including in stroke or TBI rehabilitation; and treating peripheral disorders, including hematological, cardiovascular, gastroenterological, dermatological, inflammatory, and pain disorders.
Core Innovation
The disclosure provides pyrazolo[3,4-d]pyrimidin-4-one compounds represented by Formula (I), together with pharmaceutically acceptable salts, tautomers, prodrugs, pharmaceutically active metabolites, isotopically labeled analogs, solvates and/or hydrates, including polymorphs and crystalline forms. The compound family includes specific stereochemically defined variants and related structural variants, and it is described in connection with PDE2A inhibitors.
The document further describes pharmaceutical compositions comprising a pharmaceutically acceptable carrier and an effective amount of a Formula (I) compound or a pharmaceutically acceptable salt thereof. Therapeutic uses are described for PDE2-activity-mediated neurological and CNS disorders, including cognitive impairment and modulation of the CREB pathway, as well as additional neurological and psychiatric indication categories.
The disclosure also states that isotopically labeled compounds are used for PET/SPECT imaging and for tissue distribution and target occupancy assays. The compound set is further associated with pharmacokinetic and biological performance improvements, including ADME and half-life improvements, and with memory enhancement in behavioral and cognitive assays.
Claims Coverage
The independent claim coverage centers on pharmaceutical compositions comprising a pharmaceutically acceptable carrier and one of four explicitly listed pyrazolo[3,4-d]pyrimidin-4-one compounds or pharmaceutically acceptable salts. The claim set identifies three main inventive features: the selected compound composition, treatment of PDE2-activity-mediated disorders, and treatment of specified neurological disorder categories.
Pharmaceutical composition with selected pyrazolo[3,4-d]pyrimidin-4-one compound
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound, or a pharmaceutically acceptable salt thereof, selected from four specified 3-cyclopropyl-6-methyl-1-substituted pyrazolo[3,4-d]pyrimidin-4-one compounds defined by stereochemistry and trifluoromethyl-substituted pyridyl or phenyl groups.
PDE2-activity-mediated disorder treatment using the composition
A method for treating a subject with a PDE2-activity-mediated disorder by administering an effective amount of the pharmaceutical composition.
Neurological disorder treatment using the composition with a selected disorder group
A method for treating a neurological disorder by administering an effective amount of the pharmaceutical composition to a subject diagnosed with or suffering from the disorder, where the disorder is selected from specified CNS, psychiatric, neurodevelopmental, schizophrenia/psychotic, depressive, cognitive, or neurodegenerative disorders.
The claim coverage is directed to pharmaceutical compositions containing a carrier and one of four specified pyrazolo[3,4-d]pyrimidin-4-one compounds or salts, with dependent coverage extending to treatment of PDE2-activity-mediated disorders and a range of neurological and psychiatric disorder categories.
Stated Advantages
The compounds are positioned as therapeutic agents for disorders involving PDE2-mediated mechanisms.
The description presents the compounds as intended for therapeutic use across neurological and CNS disorders, including cognitive impairment and neurodegenerative and neurodevelopmental disease categories.
ADME and half-life improvements are described for the compound set, including deuterium-labeled analogs.
Memory enhancement by Formula (I) compounds is described in the document.
Isotopically labeled compounds are used for PET/SPECT imaging and for tissue distribution and target occupancy assays.
Documented Applications
Therapeutic use for disorders involving PDE2-mediated mechanisms.
Therapeutic use in neurological and CNS disorders, including cognitive impairment or deficits and neurodegenerative and neurodevelopmental disease categories.
Peripheral disorder categories.
Isotopic imaging and radioactive use.
Pharmacological support for pyrazolo[3,4-d]pyrimidin-4-one PDE2A inhibitors using an IMAP TR-FRET PDE2A enzymatic assay with PDE2A pIC50 potency values by example number.
Behavioral and cognitive assays including contextual fear conditioning and novel object recognition.
PET/SPECT imaging.
Tissue distribution and target occupancy assays.
Therapeutic use in PDE2-activity-mediated neurological and CNS disorders, including cognitive impairment and modulation of the CREB pathway.
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