Compounds useful as potassium channel openers

Inventors

Boes, Michael

Assignees

Acousia Therapeutics GmbH

Abstract

The present invention discloses novel compounds which are useful as potassium channel openers, in particular as openers of the Kv7.4 potassium channel. The novel compounds are compounds according to formula I, wherein n=0 or 1,RL is a substituent selected from the group consisting of unsubstituted or substituted cycloalkyl groups, in particular bicycloalkyl groups, unsubstituted or substituted phenyl groups, unsubstituted or substituted thienyl groups or cyclopentathienyl groups, and unsubstituted or substituted indanyl groups, which optionally contain heteroatoms, andRR is a substituent selected from the group consisting of unsubstituted or substituted phenyl groups or unsubstituted or substituted benzyl groups, which optionally contain heteroatoms,or a stereoisomer, a tautomer, a prodrug or a salt, preferably pharmaceutically acceptable salt thereof.

Core Innovation

The patent discloses a class of potassium channel opener compounds defined by formula I in which n=0, and n=1 is also disclosed. The compounds include substituent rules in which RL is selected from unsubstituted bicycloalkyl groups and substituted thienyl groups, where the thienyl groups are substituted with at least one F-atom or Cl-atom. RR is defined as a substituted benzyl group that comprises at least one SF5 substituent, and the scope also includes stereoisomers, tautomers, prodrugs, and pharmaceutically acceptable salts.

The patent further describes RL substituent options as bicycloalkyl, including cycloalkyl and bicycloalkyl examples, and substituted thienyl groups, including examples such as cyclopentathienyl and indanyl frameworks, with optional heteroatoms and preferred halogenated and F-substituted patterns. For RR, the substituent benzyl group is described with SF5 and related halogenated or fluorinated substituents, and preferred substituent examples include CF3, OCF3, and groups such as dimethylamino, pyrrolidino, and morpholino.

A principal problem described is the treatment of disorders associated with aberrant potassium channel activity, with emphasis on inner ear hearing loss due to sensory hair cell damage or loss. The patent presents therapeutic and prophylactic use for disorders linked to potassium channel activity, including use with pharmaceutical compositions and administration routes such as transtympanic and local inner-ear administration.

Claims Coverage

The independent claim is clm-00001. It contains three main inventive feature elements that define the chemical scope of formula I and the permitted substituent selection, and it includes coverage of stereochemical and chemical forms.

Across the independent claim, the claimed compounds are defined by formula I with a constrained n and specific RL and RR selection rules, including thienyl substitution by at least one F or Cl on RL and an SF5-containing substituted benzyl on RR, while also covering stereoisomers, tautomers, prodrugs, and pharmaceutically acceptable salts.

Stated Advantages

Documented Applications