Short acting phenylalkylamine calcium channel blockers and uses thereof

Inventors

Maguire, Martin P. • Rioux, Elise • Leighton, Harry J.

Assignees

Milestone Pharmaceuticals Inc

Abstract

The present invention relates to the use of a pharmaceutically effective amount of an short-acting calcium channel blocking compound to treat ischemic heart conditions, cardiac arrhythmias, hypertensive crisis in an emergency room setting, hypertension before, during, or after surgery, no-reflow phenomenon following reperfusion, and diseases associated with decreased skeletal muscle blood flow. The invention also relates to pharmaceutical compositions formulated for use in such methods and to kits for such methods.

Core Innovation

The disclosure provides a compound class in which therapeutic compounds include a nitrile on a substituted aromatic ring, a tertiary amine linkage, and diester or carboxylate-type functionality including O-alkyl groups, together with aromatic substituents such as methoxy groups or phenolic hydroxyl groups. The compound series is presented through enumerated structure depictions and exemplified chemical identities, including variants with methoxy or alkoxy groups, ester forms, and methylamino substituents.

The document describes specific exemplified compounds within the disclosed formula class and provides chemical formation and characterization information for selected compounds, including MS molecular-ion values and oxalate salt recrystallization for derivatives. The structures are presented as defined chemical entities that support identification within the compound series.

The disclosure further states a biological characterization context including a calcium channel binding assay and Ca-channel Ki determination for compounds in Table 4, with verapamil referenced as a reference Ca-channel drug and whole brain membranes of rats mentioned in the assay context. The chemical disclosure ties the exemplified compounds to a method of treating paroxysmal supraventricular tachycardia (PSVT) by administering a therapeutically effective amount of a compound having the specified formula, including pharmaceutically acceptable addition salts and enantiomers.

Claims Coverage

The provided material includes one independent claim. It covers treatment of paroxysmal supraventricular tachycardia (PSVT) by administering a therapeutically effective amount of a compound having a specified formula, including pharmaceutically acceptable addition salts and enantiomers. The claim has one principal inventive framework: administration of the defined compound formula for PSVT treatment to a patient in need.

Across the provided material, claim coverage is focused on PSVT treatment via administration of a therapeutically effective amount of a compound defined by the specified formula, including pharmaceutically acceptable addition salts and enantiomers.

Stated Advantages

Documented Applications