Methods for treatment of heart failure
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Publication Number
US-10870656-B2
Publication Date
2020-12-22
Expiration Date
Abstract
Disclosed are methods, compositions and kits for treating or preventing heart failure. Methods of the invention treating heart failure in a mammal comprising administering to the mammal an effective amount of a thienopyrimidine compound.
Core Innovation
The disclosed invention relates to methods of treating or preventing heart failure in a mammal by administering an effective amount of a thienopyrimidine compound, optionally as a pharmaceutically acceptable salt. The specification encompasses thienopyrimidine and thieno[2,3-d]pyrimidine carboxylic acid derivatives defined by general formulae and specific chemical structures, including compounds of formula (I) and Table B.
The compounds are described by a common fused heteroaromatic scaffold with nitrogen and sulfur and a terminal carboxylic acid group. Substituent variation includes halogen substituents such as fluorine, chlorine, and bromine, as well as aryl, fused or saturated ring, alkoxy, phenoxy, alkoxycarbonyl, aminoalkyl, thiophene, cycloalkyl, cyclopentenylmethyl, thiophenylmethyl, tert-butyl, hydroxyl, methoxy, methyl, and trifluoromethyl substituents.
The disclosure further indicates therapeutic use in heart failure in mammals, including humans, with application to heart failure with preserved ejection fraction and heart failure with reduced ejection fraction. The documented subject matter also includes pharmaceutical compositions and kits for use in such treatment, and the compounds are stated to increase cyclic GMP levels.
Claims Coverage
The consolidated claim coverage identifies one independent claim directed to a method of treating heart failure in a mammal by administering an effective amount of a structure-defined compound, or a pharmaceutically acceptable salt. Dependent claims refine the clinical context, dosing, co-administration, and dosage forms, yielding six inventive features in the provided claim content.
Treating heart failure by administering a structure-defined thienopyrimidine compound
A method of treating heart failure in a mammal by administering an effective amount of a compound having the structure, formula (I), or a pharmaceutically acceptable salt thereof.
Congestive heart failure patient selection
The method identifies a mammal exhibiting congestive heart failure for treatment.
Cardiogenic shock treatment context
The method is applied to a mammal that has suffered from cardiogenic shock.
Quantified effective amount dosing range
The method uses an effective amount ranging from 0.01 to 10 mg/kg per day.
Co-administration with specified cardiovascular or metabolic drug classes
The compound is co-administered with one or more specified cardiovascular or metabolic drug classes including ACE inhibitors, angiotensin II receptor blockers or inhibitors, angiotensin-receptor neprilysin inhibitors, beta blockers, aldosterone antagonists, diuretics, anticoagulants, and cholesterol lowering drugs.
Pharmaceutical composition dosage forms for administration
The pharmaceutical composition is formulated for administration in dosage forms including a capsule, tablet, gel, powder, liquid, suspension, or emulsion.
Overall, the claim coverage centers on administering an effective amount of a structure-defined thienopyrimidine or thieno[2,3-d]pyrimidine compound, or pharmaceutically acceptable salt, for treating heart failure in a mammal. The dependent coverage narrows the condition to congestive heart failure or cardiogenic shock, adds a specified mg/kg/day range, permits co-administration with specified cardiovascular or metabolic drug classes, and specifies dosage forms.
Stated Advantages
The compounds are stated to increase cyclic GMP levels.
Documented Applications
Treating heart failure in mammals, including humans, including heart failure with preserved ejection fraction and heart failure with reduced ejection fraction.
Use in clinical phenotypes including congestive heart failure, cardiac hypertrophy, post-ischemic remodeling, and cardiogenic shock.
Use with other heart-failure agents.
Inclusion in a kit and/or pharmaceutical composition for administration.
Heart-failure prophylaxis or treatment using kits containing the compounds.
PDE9 inhibition evaluation in mouse TAC models with echocardiography and hemodynamic outcome assessment.
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