5,6-D hydro-1H-pyridin-2-one compounds

Inventors

Tran, Chinh V. • Ruebsam, Frank • Murphy, Douglas E. • Dragovich, Peter • Zhou, Yuefen • Chen, Lijian • Kucera, David • Blatter, Fritz • Viertelhaus, Martin

Assignees

Anadys Pharmaceuticals Inc

Abstract

The invention is directed to 5,6-dihydro-1H-pyridin-2-one compounds of Formula IwhereinX is N, andA isand compounds used to synthesize the compounds of Formula I.

Core Innovation

The disclosure provides chemical structures for functionalized tricyclic benzo[1,2,4]thiadiazine derivatives and related benzo[1,4]thiazin-containing bicyclic aza-/oxa-tricyclic scaffold derivatives. The compounds include substituted analogs such as methanesulfonamide, benzenesulfonamide, cyclopropanesulfonamide, fluorobenzylamine-functionalized bicyclic amines, iodinated tricyclic derivatives, hydroxy/enone-related forms, and salt forms.

The chemistry described includes formation of substituted benzo-thiadiazine-containing intermediates, coupling to bicyclo[2.2.1]heptane amine esters, and conversion to functionalized tricyclic products. It further describes transformations including amide-coupling, ester hydroxy/annulation transformations, late-stage sulfonamide formation, carbamate formation, Pd-catalyzed coupling, hydrogenation, reductive amination, azide displacement/reduction, N-alkylation, and Stille-type aryl/alkenyl installation followed by hydrogenation.

The disclosure also includes cyclic β-amino acid ester intermediates and related transformations from unsaturated cyclic meso-anhydrides, bicyclic olefins including norbornene, and β-lactam routes to saturated cyclic β-amino acids. Additional routes describe desymmetrization, Curtius rearrangement and/or Hofmann degradation, reductive N-substitution with aldehydes and ketones, diastereomeric crystallization with (1S)-(+)-10-camphorsulfonic acid salts, and further functionalization of bicyclic and tricyclic intermediates.

The document reports analytical characterization for multiple examples, including 1H NMR, LC-MS, HRMS, HPLC, and chiral HPLC or chiral ee determination, with reported yields for several intermediates and final products. It also includes stereochemical scope language for Formula I compounds, including cis/trans definitions, tautomeric forms, stereoisomers, racemates, mixtures thereof, solvates, hydrates, pharmaceutically acceptable prodrugs, pharmaceutically active metabolites, and pharmaceutically acceptable salts.

Claims Coverage

The provided independent claim text is incomplete across the input items, so no complete limitations or inventive features can be reliably extracted. The claim language available refers broadly to compounds and Formula I compounds.

No inventive features can be extracted because the provided independent claim text is incomplete and only states that a compound or Formula I compounds are claimed.

Stated Advantages

Documented Applications