Heteroaromatic macrocyclic ether chemotherapeutic agents

Inventors

Horan, Joshua Courtney • Tang, Xinxing • MENTE, SCOT RICHARD • Pelish, Henry Efrem • Shair, Matthew D. • Tangpeerachaikul, Anupong

Assignees

Pharmaresources Co Ltd • Nuvalent Inc

Abstract

Disclosed are heterocyclic heteroaromatic macrocyclic ether compounds of Formula (I): pharmaceutically acceptable salts of the compounds and pharmaceutical compositions thereof. The disclosure further relates to methods of treating or preventing cancer using the heterocyclic heteroaromatic macrocyclic ether compounds, pharmaceutically acceptable salts of the compounds and pharmaceutical compositions thereof.

Core Innovation

The invention relates to methods for treating cancer in a subject by administering a therapeutically effective amount of a compound of Formula (I) or Formula (I-B), or pharmaceutically acceptable salts, enantiomers, or tautomers thereof. The compounds are defined by specific structural variables including Q is CH, Z is CR5, and defined connectivity of X and Y through the attachment points to a CH2 group bonded to the other substituent. The substituent values are constrained by the definitions of R1, each R2, each R3, R4, and R5.

For Formula (I), the structural scope is further limited by R1 being H, CH3, or CH2OH, and each R2 and each R3 being independently selected from the listed options, while R4 is H or F and R5 is H or F. For Formula (I-B), the variable definitions likewise specify Q is CH, Z is CR5, and the same constrained ranges for R1 through R5. The disclosed subject matter also describes heteroarylene substituents X and Y and their attachment-point conventions to the CH2 linkage.

The provided examples include specific synthesized compounds and intermediates, together with characterization data such as LCMS, LC/MS, and ESI-MS [M+H]+ values. The examples indicate use in the context of cancer-treatment chemotypes defined by Formula (I) and Formula (I-B), including fluorinated and halogenated aryl and heterocycle motifs, stereochemical representations, and enantiomeric forms.

Claims Coverage

The independent claims cover cancer treatment by administering therapeutically effective amounts of Formula (I) or Formula (I-B) compounds, and in several claims by administering pharmaceutical compositions containing a pharmaceutically acceptable carrier or excipient plus the compound. Across the independent claims, the inventive content is concentrated in the structural definitions for Q, Z, X, Y, and R1–R5 and in the cancer-treatment administration language.

Across the independent claims, the coverage centers on administering therapeutically effective amounts of structurally defined Formula (I) or Formula (I-B) compounds, optionally formulated with a pharmaceutically acceptable carrier or excipient. The central inventive scope is defined by Q = CH, Z = CR5, the attachment-defined X/Y framework linked through —CH2—, and the enumerated substituent options for R1–R5.

Stated Advantages

Documented Applications