Formula I Aromatic Compounds for Osteoporosis Treatment

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Solution Overview

Problem

Current treatments for osteoporosis are associated with significant side effects and lack a universal, safer option, particularly with increased longevity requiring longer drug administration.

Innovation Solution

Development of compounds represented by Formula I and their pharmaceutically acceptable salts, which stimulate bone formation, inhibit bone resorption, and modulate biological activities such as interleukin-12 production and adiponectin levels to treat and prevent osteoporosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If current osteoporosis treatments are used to treat osteoporosis, then bone density is improved, but significant side effects occur

Engineering Contradiction:
Improvebone densityVSAvoidside effects
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of aromatic compounds through systematic substitution patterns (varying R1, R2, R3, R4 groups) to optimize therapeutic efficacy while reducing side effects. The compounds of Formula I represent a series of structurally modified analogs that change physical and biological parameters to achieve better safety profiles compared to existing treatments.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs local quality by introducing specific substituent groups at different positions (R1, R2, R3, R4) on the aromatic ring structure. Each substituent can be independently selected from specific chemical groups to confer localized functional properties that enhance bone-targeting ability while minimizing systemic side effects.

Inventive Principle:
Principle #3Local quality

2Duration of action of stationary object

If current osteoporosis treatments are administered for long periods due to increased longevity, then bone protection is maintained, but cumulative side effects increase

Engineering Contradiction:
Improvetreatment durationVSAvoidcumulative side effects
Core Design Contradiction:
Duration of action of stationary objectVSObject-generated harmful factors

Solution Approach 1:

The patent develops new compound molecules that can be administered repeatedly over long periods without accumulating toxic effects. The compounds of Formula I are designed with metabolic stability and safe elimination pathways, allowing for chronic administration similar to disposable solutions that do not accumulate harmful residues.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent enables self-service by designing compounds that selectively target bone tissue through inherent molecular recognition mechanisms. The compounds automatically accumulate at the target site (bone) and are cleared from non-target tissues, reducing cumulative side effects without requiring complex dosing regimens or monitoring.

Inventive Principle:
Principle #25Self-service

3Adaptability or versatility

If a universal treatment for osteoporosis is developed, then applicability to diverse patient populations is improved, but treatment complexity increases

Engineering Contradiction:
Improveuniversal applicabilityVSAvoidtreatment complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent achieves universality by developing a series of compounds (Formula I) that can treat multiple forms of osteoporosis across different patient populations including postmenopausal women, elderly men, and patients with secondary osteoporosis. The compounds address diverse etiologies through a common mechanism of action while maintaining safety across different demographic groups.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentEP3203999B1Substituted aromatic compounds and pharmaceutical compositions for the prevention and treatment of osteoporosis
Publication Date: 2020.01.08 LIMINAL BIOSCIENCES LTD
  • EP3203999B1 patent drawingFigure 1
  • EP3203999B1 patent drawingFigure 2~3
  • EP3203999B1 patent drawingFigure 4

AI summary

The present invention concerns the use of compounds for preventing and/or treating osteoporosis, for stimulating bone formation, for stimulating bone remodeling, for stimulating the differentiation and mineralization of osteoblasts, for inhibiting bone resorption and for modulating serum level of adiponectin in a subject. These uses have been found for compounds represented by Formula I and pharmaceutically acceptable salts thereof. wherein A is C5 alkyl, C6 alkyl, C5 alkenyl, C6 alkenyl, C(O)-(CH2)n-CH3 or CH(OH)-(CH2)n-CH3 wherein n is 3 or 4; R1 is H, F or OH; R2 is H, F, OH, C6 alkyl, C5 alkenyl, C6 alkenyl, C(O)-(CH2)n-CH3 or CH(OH)-(CH2)n-CH3 wherein n is 3 or 4; R3 is H, F, OH or CH2Ph; R4 is H, F, or OH; Q is 1) (CH2)mC(O)OH wherein m is 1 or 2, 2) CH(F)-C(O)OH, 3) CF2-C(O)OH or 4) C(O)-C(O)OH.