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Diphenylcyclohexane Derivatives for Research on the Optimization of Pharmacokinetics in Blood

 Ethyl 6-[(2-cyanoethoxy)(4,4-diphenylcyclohexyloxy)phosphoryloxy]hexanoate (1) is utilized for the improvement of peptide half-life in vivo.1) Zobel et al. have found that a peptide modified with 1 has about 50-fold longer half-life time in plasma compared to a non-modified peptide. This idea is based on the notion that diphenylcyclohexyl phosphate moiety of 1 has high affinity to serum albumin.2) Furthermore, ethyl 2-[(2-cyanoethoxy)(4,4-diphenylcyclohexyloxy)phosphoryloxy]acetate (2), whose alkyl chain length is different from 1, is also available as a building block to introduce similar moiety in order to optimize pharmacokinetics of peptides in blood.
E1313

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