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The dichloroquinoxaline group extends to ICL3 forming nonpolar interactions with K346 6.35b , C347 6.36b and a cholesterol molecule in TM6, introduction of electron-donating substituents or replacement of quinoxalines by benzimidazole or quinoline at C-6 and C-7 positions led to poor tolerance 38
Subsequent clinical success demonstrated that these liabilities could be mitigated through slower absorption kinetics, extended dosing intervals, and careful titration, ultimately allowing the beneficial metabolic effects to dominate the riskbenefit profile ( 3.1 Enabling technologies in modern peptide pharmacology One of the most important developments reshaping peptide drug discovery has been the widespread adoption of long-acting peptide design strategies
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