Substituted xanthines and methods of use thereof

Inventors

Chenard, Bertrand L. • Gallaschun, Randall J.

Assignees

Boehringer Ingelheim International GmbH

Abstract

Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.

Core Innovation

The disclosure relates to substituted purine derivatives based on a purine-2,6-dione scaffold and related 1H-purine-2,6-dione derivatives. The described compounds include substituted benzyl and heteroatom-containing linkers, phenoxy variants bearing trifluoromethyl or trifluoromethoxy substituents, and other aryl, heteroaryl, hydroxyalkyl, alkoxy, and halogenated substituent patterns. The structures are presented with synthetic preparation and characterization data, including LCMS, HPLC, and 1H NMR, together with example and structure identifiers.

The disclosure also describes synthetic preparation and characterization data for named intermediates and substituted purine dione compounds. Representative intermediates and products include chloromethylated heteroaryl building blocks, purine and pyrimidine derivatives, and compounds bearing side-chain modifications such as hydroxyethyl, hydroxypropyl, hydroxybutyl, tetrahydro-2H-pyran-2-yloxy, pyridinylmethyl, dimethylaminoethyl, thiazolylmethyl, sulfonyl, and sulfonamide-related moieties. The examples further include reported yields and embedded chemical structure representations and identifiers.

The therapeutic aspect is directed to treatment of a TRPC5 mediated disorder in a subject, wherein the TRPC5 mediated disorder is post-traumatic stress disorder. The method comprises administering to the subject a compound of a specified formula, or a pharmaceutically acceptable salt thereof, to thereby treat the subject. The claim-linked compound selection is grounded in the disclosed substituted purine derivative structures and their formula/structure depictions.

Claims Coverage

The consolidated claim set includes two independent method claims. Both are directed to treating a TRPC5 mediated disorder, specifically post-traumatic stress disorder, by administering a compound of a specified formula; one independent claim expressly includes pharmaceutically acceptable salts. Across the independent claims, the inventive focus is formula-defined substituted purine compounds used for treatment.

The claims are directed to treating post-traumatic stress disorder as a TRPC5 mediated disorder by administering a compound defined by a specified formula, with one independent claim including pharmaceutically acceptable salts. Dependent claim refinements narrow the compound to the formula/structure shown and to named substituent elements such as HO, Cl, O, N, and OCF3.

Stated Advantages

Documented Applications