Substituted pyridine and pyrazine compounds as PDE4 inhibitors

Inventors

Bollu, Venkataiah • Breitenbucher, James • Kaplan, Alan • Lemus, Robert • Lindstrom, Andrew • VICKERS, Troy • Wilson, Mark E. • Zapf, James

Assignees

Dart Neuroscience LLC

Abstract

The invention provides a chemical entity of Formula (I) wherein R1, R2, R3, R4, 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, and radioactive treatments; and therapies, including inhibiting PDE4, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating peripheral disorders, including inflammatory and renal disorders.

Core Innovation

The disclosed invention relates to compounds of Formula (I) and related embodiments, including substituted heteroaryl-containing scaffolds and substituted pyridine, pyrazine, pyrimidine, triazole, imidazole, pyrazole, tetrazole, oxazole, and thiazole motifs. The compounds include pharmaceutically acceptable salts, prodrugs, metabolites, solvates, hydrates, conformers, polymorphs, isotopically labeled compounds, and related derivative forms.

The disclosure emphasizes broad structural variability through substituent definitions and multiple example compounds, including chloro, fluoro, difluoromethoxy, difluoromethyl, trifluoromethyl, methoxy, ethoxy, cyclopropoxy, carbonitrile, amine, carboxamide, carboxylate, and hydroxymethyl substituents. The examples include heteroaryl-linked structures and triazole-bearing side chains, with regioisomer confirmation, purification, and characterization by 1H NMR, LC/MS, LCMS, and reported [M+H] values.

The compounds are characterized as PDE4 inhibitors and are placed in CNS-related therapeutic contexts. The examples and characterization data support the reported compound family and its pharmacological evaluation as PDE4 inhibitors.

Claims Coverage

The provided independent claim coverage is broad and centers on a compound selected from specified groups and pharmaceutically acceptable salts thereof. Across the input items, the explicitly stated inventive features are compound selection from specified or unspecified groups and pharmaceutically acceptable salts.

The claims are consistently presented at a broad selection level, covering compounds selected from specified groups and pharmaceutically acceptable salts. No further independent-claim refinements are explicitly recoverable from the provided claim text excerpts.

Stated Advantages

Documented Applications