Inhibitors of cyclin-dependent kinases

Inventors

Kanouni, Toufike • Arnold, Lee D. • Kaldor, Stephen W. • Murphy, Eric A. • Tyhonas, John

Assignees

Fount Service Corp • Kinnate Biopharma Inc

Abstract

Provided herein are inhibitors of cyclin-dependent kinases (CDKs), pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.

Core Innovation

The disclosure relates to a compound, or a pharmaceutically acceptable salt or solvate thereof, selected from a group of substituted acrylamide-like structures. The selected compounds share a structural motif including a pyrrolidine-1-carbonyl linked to an aryl group bearing an acrylamide or related unsaturated amide moiety, together with substituted heteroaryl amino substituents, especially pyrimidin-2-yl and related chlorinated, methoxylated, cyano, fluoro, trifluoromethyl, cyclopropoxy, pyrazinyl, pyridinyl, pyrazolyl, and thiazolyl variants.

The document further specifies stereochemical variants within the selected group, emphasizing (R)-configured compounds and, for some members, related stereochemical designations for but-2-enamide or enesulfonamide members. The scaffold also includes variants such as acrylamide, N-methylacrylamide, propiolamide, cyanoacrylamide, cyanoacetamide, oxirane-2-carboxamide, and ethenesulfonamide forms, with corresponding variation on the phenyl and heteroaryl portions.

The disclosure additionally describes multiple synthetic examples and characterization data for members of the scaffold family. These examples include preparation of intermediates, conversion to corresponding amines, coupling to install acrylamide-like linkages, and characterization by 1H NMR and mass-related values, including reported yields and calculated/found [M+H] values.

Claims Coverage

The consolidated claim coverage centers on a single independent selection claim for a group of specific (R)-configured substituted acrylamide-like compounds, or pharmaceutically acceptable salts or solvates thereof. The inventive features repeatedly present across the inputs are the chiral pyrrolidine-1-carbonyl core, a substituted heteroaryl amino motif, and an acrylamide or related unsaturated amide linkage, with numerous named substitution options and stereochemical constraints.

Overall, the claims are directed to a defined family of selected (R)-configured substituted acrylamide-like compounds, including pharmaceutically acceptable salts or solvates, built around a pyrrolidine-1-carbonyl scaffold, substituted heteroaryl amino linkage, and an acrylamide or related unsaturated amide region.

Stated Advantages

Documented Applications