Spiro Compounds Inhibit SCD-1 to Reduce Triglycerides
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Solution Overview
Problem
Current therapeutic approaches lack effective agents specifically targeting stearoyl-CoA desaturase (SCD) for the treatment of hyperlipidemia, diabetes, obesity, lipid metabolism abnormalities, and related cardiovascular diseases, as existing medications primarily focus on lifestyle improvements and general lipid lowering rather than specific SCD inhibition.
Innovation Solution
A compound represented by formula (I), which exhibits superior SCD inhibitory action, particularly inhibiting SCD-1, leading to reduced triglyceride levels, enhanced insulin signaling, and decreased body weight by promoting energy consumption, is developed for use as a medicament to treat obesity, diabetes, and metabolic syndrome.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If SCD activity is increased to produce monounsaturated fatty acids, then fat synthesis and energy storage are improved, but lipid metabolism abnormality and fatty liver occur
Solution Approach 1:
The invention changes the metabolic parameter by inhibiting SCD enzyme activity, thereby reducing the conversion of saturated fatty acids to monounsaturated fatty acids. This parameter change prevents the accumulation of triglycerides in the liver and improves lipid metabolism without completely blocking fatty acid synthesis pathways
Solution Approach 2:
The patent uses SCD inhibitor compounds as intermediary substances that selectively block the SCD enzyme. These compounds act as mediators between saturated fatty acids and monounsaturated fatty acids, controlling the desaturation process to prevent harmful lipid accumulation while maintaining metabolic balance
2Reliability
If SCD1 is deleted to improve fatty liver and obesity, then energy consumption increases and insulin signal enhances, but complete deletion may cause unintended metabolic disruptions
Solution Approach 1:
Instead of complete SCD1 deletion, the invention applies partial inhibition through selective SCD inhibitor compounds. This partial action achieves the beneficial effects of reduced fatty liver and improved insulin sensitivity while maintaining enough SCD activity to preserve essential metabolic functions and adaptability
Solution Approach 2:
The invention segments the approach to SCD inhibition by using selective chemical compounds that target specific SCD isoforms (particularly SCD1) while sparing other desaturase enzymes. This segmentation allows selective modulation of lipid metabolism pathways without disrupting overall metabolic versatility
Data Source
AI summary
The present invention aims to provide a novel SCD inhibitor.The present invention relate to SCD inhibitor comprising A compound represented by the formula (I)whereinR is an optionally substituted cyclic group or an optionally substituted carbamoyl group, provided that R is not an optionally substituted 7-pyrido[2,3-d]pyrimidyl group;ring A is an optionally further substituted pyridazine ring;R1, R2, R3, R4, R11, R12, R13 and R14 are each independently a hydrogen atom or a substituent, or R1 and R11 in combination, R2 and R12 in combination, R3 and R13 in combination, or R4 and R14 in combination optionally form an oxo group, or R2 and R4 in combination optionally form a bond or an alkylene cross-linkage;m and n are each independently an integer of 0 to 2;ring B is an optionally substituted ring, provided that the two atoms constituting ring B, which are adjacent to the spiro carbon atom, are not oxygen atoms at the same time,or a salt thereof, or a prodrug thereof.