Peptidyl prodrugs that resist P-glycoprotein mediated drug efflux

摘要

A method of treating a patient for a condition wherein the bioactive agent of choice is DRUG, wherein DRUG is a substrate that is effluxed by the P-gp transporter, is provided, the method comprising administering to the patient an effective amount of a compound of formula (I):DRUG-X—Y_(n)—Z_(n′)—Z′_(n″)—R  (I)wherein each X, Y, Z, and Z′ is independently Met, Val, Thr, Tyr, Trp, Ser, Ala, or Gly; R is H or an amino-protecting group; n is 1, and each n′, or n″ is independently 0 or 1; or a pharmaceutically acceptable salt thereof, with the proviso that DRUG is not acyclovir or ganciclovir and that DRUG is non-peptidyl.