Benzenesulfonamide derivatives and uses thereof

Inventors

Gunning, Patrick T. • PARK, Ji Sung • Ahmar, Siawash • CABRAL, Aaron D. • TIN, Gary K.C. • RASHEED, Sana • ABDELDAYEM, Ayah • Armstrong, David • FRERE, Geordon A. • QUILATES, Erica J. • ROSA, David Alexander • Gozhina, Olga • OMEARA, JEFFREY ALAN • Simpson, Graham • ZOPPI, Vittoria

Assignees

2692372 Ontario Inc • Dunad Therapeutics Ltd

Abstract

Provided herein are benzenesulfonamide derivatives having Formula (III), pharmaceutical compositions comprising said compounds, and method for using said compounds for disrupting proteins/polypeptides, protein/polypeptide function, and for the treatment of diseases through the disruption of proteins or polypeptides involved in the etiology of the disease. Said compounds comprise fluorinated benzene sulfonamide structures.

Core Innovation

The disclosure is directed to a compound represented by a specified structural framework in which G1 is a protein binder, and R1, R2, R3, and R4 are defined by broad substituent options. The structure includes cyano, oxo/oxy, thio/oxo, carbonyl-related motifs, sulfur-containing and oxygen-containing substituent possibilities, nitrogen-containing substituents, and diverse alkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups, and the compound includes salts or solvates.

The framework further allows two R3 groups on the same nitrogen atom to be joined to form substituted or unsubstituted C2-C7 heterocycloalkyl, and R4 is defined as substituted or unsubstituted C3-C8 cycloalkyl, C2-C7 heterocycloalkyl, aryl, or heteroaryl. The provided examples implement benzenesulfonamide and tetrafluorobenzenesulfonamide cores with N,N-dimethylsulfonamide, N-aryl, N-substituted derivatives, and fluorinated benzenesulfonamide ring substitution patterns, including fluoro, methoxy, benzyloxy, hydroxy, cyano, fluoro-methoxy, difluoromethoxy, trifluoromethoxy, and related alkoxy or heteroalkoxy substituents.

The document also associates the compounds with protein interaction contexts, including covalent modification of proteins and polypeptides. Dependent claim coverage specifies covalent bond formation with a sulfur atom of a cysteine residue and contacting-based binding or modification, including use of the compound or a salt or solvate form.

Claims Coverage

The provided claim coverage centers on one independent compound claim defining a protein-binder scaffold with multiple variable substituents and explicit salt or solvate coverage. The identified dependent claims add four inventive refinements: protein-binder ring scope, covalent cysteine-sulfur modification of proteins, covalent cysteine-sulfur modification of polypeptides by contacting, and binding of the compound to a polypeptide by contacting.

Overall, the claim coverage is directed to a protein-binder compound scaffold with broad substituent variability and explicit salt or solvate coverage. The dependent claims narrow G1 to specified aryl or heteroaryl sets and add covalent cysteine-sulfur modification and binding by contacting.

Stated Advantages

Documented Applications