Glucose uptake inhibitors

Inventors

Liu, Kevin G. • Olszewski, Kellen L. • Kim, Ji-In • Poyurovsky, Masha V. • Morris, Koi • Yu, Xuemei • LAMARQUE, CHRISTOPHE

Assignees

Kadmon Corp LLC

Abstract

This invention provides compounds that modulate glucose uptake activity and cellular transport/uptake of glucose, and particularly GLUTS3, but also including but not limited to GLUT1-14 (SLC2A1-SLC2A14). Compounds of the invention are useful for treating diseases, including cancer, autoimmune diseases and inflammation, infectious diseases, and metabolic diseases.

Core Innovation

The invention relates to heterocyclic amide compounds having a phenoxy-linked quinazolinyl, fluoroquinazolinyl, thieno[3,2-d]pyrimidinyl, pyrido[4,3-d]pyrimidinyl, pyrano[4,3-d]pyrimidinyl, furo[3,4-d]pyrimidinyl, purinyl, pyrazolo[3,4-d]pyrimidinyl, or pyrrolo[2,3-d]pyrimidinyl core bearing an (1H-pyrazol-4-yl)amino or (1H-pyrazol-3-yl)amino substituent. The compounds are defined by a phenoxy-acetamide or related amide framework with variable N-substitution, including tert-butyl, isopropyl, cyclobutyl, cyclopentyl, sec-butyl, tert-pentyl, and related substituted amides, together with pharmaceutically acceptable salts thereof.

The disclosed scaffold is diversified by quinazoline ring substitution patterns that include fluoro, chloro, methoxy, ethoxy, isopropoxy, propoxy, cyclopropoxy, cyclobutoxy, cyclopentyloxy, trifluoromethoxy, trifluoromethyl, methylthio, methylsulfonyl, and related ether or halo substituents at different ring positions. The pyrazolyl amino group is also varied by pyrazol-3-yl or pyrazol-4-yl identity and by substituted pyrazoles, including methyl-, phenyl-, benzyl-, isopropyl-, cycloalkyl-, and halogenated variants as recited in the compound sets. The claim language further includes alternative fused or extended heterocycle motifs while retaining the phenoxy and pyrazolylamino features.

The partial disclosure emphasizes structurally defined compound families and representative examples, with analytical characterization by MS and NMR for multiple members. It also includes explicit salt forms such as bis trifluoroacetic acid salts, tris trifluoroacetic acid salts, and HCl salts for particular compounds. The problem being solved is not explicitly stated, and the document focuses on provision and characterization of the claimed heterocyclic amide compounds.

Claims Coverage

The provided material includes one independent claim directed to a broad set of specific heterocyclic amide compounds, together with pharmaceutically acceptable salts. Across the claim set, there are four recurring inventive features: the phenoxy-linked heteroaromatic scaffold, the pyrazolylamino substituent, the variable N-substituted acetamide or related amide side chain, and the optional salt form; a dependent claim further adds a pharmaceutical dosage form with a pharmaceutically acceptable excipient.

The claim coverage is directed to a structurally defined family of phenoxy-linked heterocyclic amide compounds built around a quinazoline or related fused heteroaromatic core bearing a pyrazolylamino substituent, with enumerated ring substitutions and variable N-substituted amide side chains. The claim set also expressly includes pharmaceutically acceptable salts, and one dependent claim adds a pharmaceutical dosage form containing a pharmaceutically acceptable excipient.

Stated Advantages

Documented Applications