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Metabolism of macrocyclic drugs

Metabolite Tales Blog

Not only this, the reduction in rotatable bonds and consequent reduction in susceptibility to metabolism is an additional benefit [4]. The resulting macrocyclic structure was found to be associated with improved metabolic stability and low propensity for P-gp efflux compared to the acyclic analog [13]. 20 (March 20, 2014).

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Metabolism of de novo designed macrocyclic drugs

Metabolite Tales Blog

Not only this, the reduction in rotatable bonds and consequent reduction in susceptibility to metabolism is an additional benefit [4]. The resulting macrocyclic structure was found to be associated with improved metabolic stability and low propensity for P-gp efflux compared to the acyclic analog [13]. 20 (March 20, 2014).

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N-glucuronidation: the human element

Metabolite Tales Blog

To curb glucuronidation at that position a gem-dimethyl group was incorporated which not only boosted metabolic stability, but also resulted in increased potency of the final lead compound. Paine and Aleksandra Galetin (2014). Drug Metabolism and Disposition 42 (4) 650-664; [link]. [2] Polli, Mary F.

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Efficient trajectories

Molecular Design

Design decisions in lead optimization are typically supported by assays for a range of properties such as solubility, permeability, metabolic stability and off-target activity as well as pharmacokinetic studies.