Rimonabant-based fast follower approach

1) Identifying the metabolic weak spots on rimonabant and improving the metabolic stability to gain advantage of longer plasma half-life. 

Rimonabant CBi Ki 1.8 nM CB2Ki 514nM Plasma/brain ratio 1.2 

2) Improving selectivity against CB2 receptors to avoid CB2 receptor-associated side effects. 

3) Restricting CBiR antagonists in the peripheral system to avoid CNS side effects. 

SAR analysis of rimonabant-based series compounds suggested the following  

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