Pyrrolidine Compounds for Sustained Lp(a) Reduction
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Solution Overview
Problem
There is a need for pharmaceutical treatments to lower elevated lipoprotein(a) (Lp(a)) levels, as current treatments are inadequate for managing cardiovascular diseases, particularly lipid disorders, and existing therapies do not effectively manage Lp(a) levels, which are an independent risk factor for cardiovascular events.
Innovation Solution
Development of pyrrolidine compounds and their pharmaceutically acceptable salts, which can be administered to reduce plasma Lp(a) levels, potentially offering a new treatment option for cardiovascular diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If apheresis is used to filter blood to remove LDL and Lp(a), then Lp(a) levels are reduced, but the treatment requires repeated sessions every two weeks and has only temporary effects
Solution Approach 1:
The patent uses antisense oligonucleotides as intermediary molecules that bind to Lp(a) in the blood, forming complexes that are then cleared by the reticuloendothelial system. This mediator approach provides sustained reduction of Lp(a) levels without requiring repeated apheresis procedures, resolving the contradiction between effective Lp(a) removal and temporary treatment duration.
2Quantity of substance
If current standard of care therapies (statins, fibrates, niacin) are used, then lipid profiles are managed, but Lp(a) levels remain unaffected
Solution Approach 1:
The patent segments the lipid management problem by specifically targeting Lp(a) with antisense oligonucleotides, separating it from the broader lipid profile management handled by statins, fibrates, and niacin. This segmented approach allows standard therapies to continue managing overall lipid levels while the antisense compound specifically addresses Lp(a), providing versatile treatment that simultaneously manages multiple lipid parameters.
3Ease of operation
If no pharmaceutical treatment is available for Lp(a), then treatment options are limited, but apheresis procedures are complex and require repeated sessions
Solution Approach 1:
The patent replaces the mechanical apheresis system with a biochemical approach using antisense oligonucleotides. Instead of mechanically filtering blood through complex apheresis equipment, the antisense compounds chemically bind to Lp(a) and facilitate its clearance through natural biological pathways. This substitution simplifies treatment administration to oral or injectable medication while maintaining effective Lp(a) reduction.
Data Source
AI summary
The present invention provides compounds of the Formulawherein L is selected from the group consisting of —CH2NHCH2—, —CH2NH—, —NH—, —S—, —S(O)—, —S(O)2—, —O—, —OCH2—, —OCH2CH2O—, —NHSO2NH—,or a pharmaceutically acceptable salt thereof; a compound of the formula:processes for preparing the compounds and their salts, a pharmaceutical composition, and methods of treating patients in need of such treatment.