Cyclopropanamine LSD1 Inhibitor Selectivity
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Solution Overview
Problem
Current LSD1 inhibitors lack superior LSD1 inhibitory action and selectivity, which limits their effectiveness as medicaments for cancer, schizophrenia, Alzheimer's disease, Parkinson's disease, and Huntington's chorea.
Innovation Solution
A cyclopropanamine compound with a specific structural formula that exhibits superior LSD1 inhibitory action and high selectivity, formulated as a medicament for prophylactic or therapeutic use in various diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing LSD1 inhibitors are used, then LSD1 inhibition is achieved, but selectivity and inhibitory action are insufficient
Solution Approach 1:
The patent applies local quality by introducing specific substituent patterns at defined positions of the core molecular structure. Formula (1) specifies particular groups at R1-R6 positions (halogen, alkyl, alkoxy, etc.) that locally modify the molecule's interaction properties with LSD1, achieving both strong inhibition and selectivity through localized structural optimizations rather than global changes
Solution Approach 2:
The patent employs parameter changes by systematically varying substituent types, positions, and chain lengths in Formula (1) to optimize LSD1 inhibition. By changing parameters such as the nature of R groups (halogen vs alkyl vs alkoxy), their positions on the aromatic rings, and the length of alkyl chains in the linker region, the invention achieves enhanced and selective LSD1 inhibition
2Reliability
If LSD1 inhibition is enhanced, then therapeutic effectiveness improves, but side effects may increase
Solution Approach 1:
The patent applies preliminary anti-action by designing Formula (1) with high LSD1 selectivity that preemptively prevents off-target effects. The specific molecular structure with defined substituent patterns at R1-R6 positions ensures preferential binding to LSD1 over other enzymes, thereby preventing side effects before they can occur by avoiding non-selective inhibition of other biological targets
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compound demonstrates enhanced LSD1 inhibitory activity, reducing side effects and showing promise in treating cancer, psychiatric disorders, neurodegenerative diseases, and other conditions by suppressing histone H3K4 methylation decreases and promoting neural plasticity and BDNF production.
Implementation Method 1
LSD1 is a demethylation enzyme of histone, catalyzes a demethylation reaction of a monomethylated product and a dimethylated product of the 4th lysine residue of histone H3 (H3K4me1/2), and forms formaldehyde as a by-product
Implementation Method 2
LSD1 forms a complex with flavin adenine dinucleotide (FAD) which is a kind of coenzyme, and FAD promotes oxidation of lysine residue by enzymes as a redox mediator
Data Source
AI summary
The present invention provides a compound having a lysine-specific demethylase 1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for cancer, and central nervous system diseases, and the like. The present invention relates to a compound represented by the formula wherein A is a hydrocarbon group or heterocyclic group optionally having substituent(s); R is H, a hydrocarbon group or heterocyclic group optionally having substituent(s); A and R are optionally bonded to each other to form a ring optionally having substituent(s); Q1, Q2, Q3 and Q4 are each a hydrogen atom or a substituent; Q1 and Q2, and Q3 and Q4, are each optionally bonded to each other to form a ring optionally having substituent(s); X is H, an acyclic hydrocarbon group or saturated cyclic group optionally having substituent(s); Y1, Y2 and Y3 are each H, a hydrocarbon group or heterocyclic group optionally having substituent(s); X and Y1, and Y1 and Y2, are each optionally bonded to each other to form a ring optionally having substituent(s); and Z1, Z2 and Z3 are each H or a substituent, or a salt thereof.