Substituted [1,2,4]triazolo[1,5-a]pyrimidin-7-yl compounds as PDE2 inhibitors

Inventors

Breitenbucher, James • Freestone, Graeme • Gomez, Laurent • Lemus, Robert • Ly, Kiev • McCarrick, Margaret • Vernier, William • VICKERS, Troy

Assignees

Dart Neuroscience LLC

Abstract

The invention provides a chemical entity of Formula (I): wherein R1, R2, X, 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 as disclosed herein, 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, neurodegenerative diseases, and trauma-dependent losses of function; treating stroke, including cognitive and motor deficits during stroke rehabilitation; facilitating neuroprotection and neurorecovery; enhancing the efficiency of cognitive and motor training, including animal skill training protocols; and treating peripheral disorders, including hematological, cardiovascular, gastroenterological, and dermatological disorders.

Core Innovation

The patent discloses substituted [1,2,4]triazolo[1,5-a]pyrimidin-7-yl compounds as PDE2 inhibitors, including morpholine-containing compounds and piperidine or related scaffold members. The compounds are represented by specific (2S)-configured structures with substituted benzoyl or carbonyl aryl groups, pharmaceutically acceptable salts, and broader variable substituent definitions within the Formula (I) framework.

The invention is directed to inhibition of PDE2 activity by exposing PDE2 to an effective amount of the claimed compound or a pharmaceutically acceptable salt thereof. The claim coverage further links PDE2 inhibition to pharmaceutical compositions and to methods of treating disorders in subjects having or diagnosed with disorders treated by PDE2 inhibition.

The therapeutic focus is on neurological disorders selected from enumerated CNS, psychiatric, cognitive, dementia, delirium, developmental, and related categories, including schizophrenia spectrum or psychotic disorder and neurodegenerative disease groupings. The document also includes examples of substituted triazolopyrimidine derivatives with variable aryl and heteroaryl substituents, and characterization data reported for selected compounds.

Claims Coverage

The independent claims cover three specific (2S)-configured substituted triazolo[1,5-a]pyrimidin-7-yl morpholine compounds, each as a compound or pharmaceutically acceptable salt, together with methods of inhibiting PDE2 activity and treating selected neurological disorders. In addition, the claim families cover pharmaceutical compositions comprising a pharmaceutically acceptable excipient and the claimed compound or salt. Across the independent families, the main inventive features are the exact compound structures, PDE2 inhibition, and therapeutic use in enumerated neurological disorder categories.

Across the independent claims, the coverage centers on three specific (2S) morpholine-linked 5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl compounds bearing distinct substituted benzoyl groups, each with pharmaceutically acceptable salt options. The dependent claims extend the compounds into pharmaceutical compositions and into methods of inhibiting PDE2 activity and treating broadly enumerated neurological disorders, including psychotic disorders and selected neurodegenerative disease categories.

Stated Advantages

Documented Applications