Diphenylcyclohexane Derivatives for 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⁾ According to Zobel’s report, it is 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 improve pharmacokinetics of peptides in blood.