MEK inhibitors and therapeutic uses thereof

Inventors

Hall, Brett Matthew • Decorte, Bart Lieven • King, Peter John • Leenders, Ruben • WEGERT, Anita • Fowler, Kevin • Kolitz, Sarah • DOODEMAN, Robin • Poelakker, Jarno • Folmer, Rutger Henk Adriaan

Assignees

Immuneering Corp

Abstract

The present disclosure provides compounds, compositions containing such compounds, and methods of designing, developing, producing and preparing compounds represented by general Formula (I), including pharmaceutically acceptable salts thereof or a synthetic intermediate thereof: The compounds act as MEK inhibitors and are capable of displaying one or more beneficial therapeutic effects, including treating cancer.

Core Innovation

The invention relates to compounds defined by Formula (IIb) and Formula (IIa), or pharmaceutically acceptable salts thereof. The compounds are characterized by structural relationships among Z, R2, L, Z1, and Z2, where Z is C or N, R2 is L, L is a linkage of Z1 and Z2, and Z1 is CH2. In Formula (IIb), Z2 is defined as NR5R5′ or optionally substituted, and the scope is further narrowed by permitted substituent selections and selected members from depicted structures.

The invention further constrains substituent choices by defining R5 and R5′, where present, as independently C1 to C6 alkyl or, in Formula (IIa), independently H, deuterium, or C1 to C6 alkyl. R6 is limited to H, deuterium, halogen, or C1 to C6 alkyl, and n is 1, 2, 3 or 4 in the relevant Formula (IIb) alternative. Formula (IIa) additionally specifies R3 as fluoro, X as O, Y as O, and Z2 as selected from NR5R5′ or C3 to C8 heterocyclyl.

The disclosure includes selected compounds from enumerated groups and Table A-type selections, together with pharmaceutically acceptable salts. The document also describes substituted coumarin-based, coumarin/benzopyran chromen-2-one, and coumarin/sulfonamide compound families using the same formula-based structural framework and constrained variable selections.

Claims Coverage

This consolidated claim coverage includes four independent claims directed to compounds of Formula (IIb) or the structure depicted in Formula (IIa), together with pharmaceutically acceptable salts. The main inventive features are the Z/R2/L/Z1/Z2 scaffold definition, enumerated substituent sets for R5/R5′, R6, and R8, the n limitation in one Formula (IIb) alternative, and the fixed atom/substituent selections in Formula (IIa), including R3 as fluoro and X and Y as O.

Overall, the independent claims cover Formula (IIb) and Formula (IIa) compounds, or pharmaceutically acceptable salts thereof, defined by the Z/Z1/Z2 scaffold and linkage L with Z1 fixed as CH2. The claims further restrict substituent identity through enumerated sets for R6 and, where applicable, R5 and R5′, while the Formula (IIa) claim additionally fixes R3 as fluoro and X and Y as O and defines Z2 by specific group types.

Stated Advantages

Documented Applications