Substituted benzoxazole and benzofuran compounds as PDE7 inhibitors

Inventors

Santora, Vincent John • Chen, Mi • Chung, DeMichael

Assignees

Dart Neuroscience LLC

Abstract

Substituted benzoxazole and benzofuran chemical entities of Formula (I): wherein, V, W, X, Y, Z, and m have any of the values described herein and compositions comprising such chemical entities; processes for making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies; detection and imaging techniques; radioactive treatments; and the treatment of one or more disorders, including neurological, cognitive, immunological, and inflammatory disorders, as well as other conditions and diseases involving PDE7 or cyclic nucleotide signaling.

Core Innovation

The invention relates to pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (1), or a pharmaceutically acceptable salt thereof. The compounds are selected from specifically named 5-chloro spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1′-cyclohexane]-7-one derivatives with defined 2-position sidechain substituents, including azabicyclo, methoxy-methylazetidinyl, hydroxymethylpyrrolidinyl, and dimethylaminoethyl(methyl)amino methyl motifs. The disclosed group shares the same core spiro-fused quinazoline scaffold while varying substituents at the 2-position.

The invention further relates to methods of inhibiting or relieving a disorder or ameliorating a symptom of a disorder having an aberrant or dysregulated signaling pathway mediated by PDE7 in a subject. The method comprises administering to the subject in need thereof a compound of Formula (1), or a pharmaceutically acceptable salt thereof, selected from the same specifically named group of compounds. The PDE7-mediated signaling linkage defines the therapeutic targeting of the compound and the intended clinical outcome.

The patent content also includes specific compound examples and characterization data for multiple substituted spiro derivatives within the same scaffold family, including 1H NMR data and [M+H]+ values. These examples support structural embodiments of the Formula (1) compounds while maintaining the shared 5-chloro and spiro scaffold features.

Claims Coverage

Two independent claims are present: a pharmaceutical composition claim and a therapeutic method claim. In total, the recurring inventive features are the specific Formula (1) compound selection within a pharmaceutically acceptable carrier composition, and the same compound selection used in a method of inhibiting or relieving a disorder or ameliorating a symptom where the disorder involves PDE7-mediated aberrant or dysregulated signaling.

Claim coverage is directed to specific Formula (1) spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1′-cyclohexane]-7-one derivatives with a 5-chloro core, used either in pharmaceutical compositions or in a PDE7-mediated therapeutic method. The method claim further requires that the disorder involve aberrant or dysregulated PDE7-mediated signaling.

Stated Advantages

Documented Applications