新方法和新术.pptVIP

Medicinal chemistry Chapter 13 New Methods and Techniques College of Pharmacy, SDU Prodrug The term prodrug, which was used initially by Albert HI, is a pharmacologically inactive compound that is converted into an active drug by a metabolic biotransformation. A prodrug also can be activated by a nonenzymatic process such as hydrolysis, but in this case the compounds generally are inherently unstable and may cause stability problems. The prodrug to drug conversion can occur before absorption, during absorption, after absorption, or at a specific site in the body. In the ideal case a prodrug is converted to the drug as soon as the desired goal for designing the prodrug has been achieved. Soft Drug Soft drugs are biologically active drugs designed to have a predictable and controllable metabolism to nontoxic and inactive products after they have achieved their desired pharmacological effect. The molecule could be deactivated and detoxified shortly after it has exerted its biological effect, the therapeutic index could be increased, providing a safer drug. Feature It has a close structural similarity to the lead; It has a metabolically sensitive moiety built into the lead structure; The incorporated metabolically sensitive spot does not affect the overall physicochemical or steric properties of the lead compound; Advantages Elimination of toxic metabolites, thereby increasing the therapeutic index of the drug; Avoidance of pharmacologically active metabolites that can lead to long-term effects; Elimination of drug interactions resulting from metabolite inhibition of enzymes; Simplification of pharmacokinetic problems caused by multiple active species. The difference between prodrugs and soft durgs The concepts of prodrugs and soft drugs are opposite, as follow: A prodrugs is an inactive compound that requires a metabolic conversion to the active form; A soft drug is pharmacologically active and uses metabolism as a means of promoting excretion. However,