US 12,195,419 B2 · Glutamine antagonists and uses thereof

Abstract

Glutamine antagonists and their use for treating oncological, immunological, and neurological diseases are disclosed. Also disclosed are methods for treating an oncological, immunological, infectious or neurological disease or disorder, the method comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof. Also disclosed are methods of enhancing the effects of an immune checkpoint inhibitor, enabling a subject to respond to an immune checkpoint inhibitor, or enabling the toxicity or the dose or number of treatments with an immune checkpoint inhibitor to be reduced, comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof, and an immune checkpoint inhibitor. Also disclosed are methods for treating an oncological, immunological, infectious or neurological disease or disorder that is refractory to checkpoint inhibitor therapy, the method comprising administering to a subject in need thereof, and having the refractory disease or disorder, a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof.

Claims24

Dependent claims

A compound having a structure of formula (Ih):

wherein:
R6 is selected from the group consisting of H, —(CH2)t—CH(NH—C(CH3)(═O))—(CH2)t—R9, —C(═O)—X2—R10, and one or more substituted or unsubstituted amino acids, wherein the one or more substituted or unsubstituted amino acids is bound to the nitrogen atom adjacent to R6 through a carboxyl moiety of the one or more substituted or unsubstituted amino acids, wherein X2 is present or absent and, when present, is selected from the group consisting of —O—, —O—(CH2)q—, —(CH2)t—, and —(CH2)v—CH═CH—(CH2)v—, wherein q and t are each independently selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, and 8, each v is independently selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, and 8, and R9 and R10 are each independently selected from the group consisting of straight chain or branched alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
or an ester or pharmaceutically acceptable salt thereof.

Dependencies are inferred from the claim text.

Glutamine antagonists and uses thereof

Life of this patent

Glutamine antagonists and uses thereof

Life of this patent

Abstract

Claims24