Bioisosteres are a class of compounds or groups,these compounds with similar molecular shapes or volume, similar electronic distribution, and similar physical properties. Bioisosteres play a role in the same related biochemical system as agonist or antagonist, which possessed in related biological activities. The amide structure can be an important part of drugs and a constituent of a pharmacophore. However, the presence of this moiety can also be responsible for some significant drawbacks about drug molecular, including metabolic instability, toxicity, as well as limited passive diffusion across biological membranes. To avoid some of these shortcomings while retaining the desired attributes of the amide moiety, bioisosteric replacement of the amide moiety in lead compounds is an effective method. Through the amide bioisosteric replacements, other aims would be goal such as increasing the target potency and selectivity, developing new structures to expand or break through the patents and decreasing the difficulty of the synthesis of the compounds. This review focuses on the application of the replacement between amide and amide bioisosteres in the optimization of lead compounds in recent five years. We wish our review would offer a new thinking in the design and optimization of the compounds in the research and development of the new drugs.

Contents
1 Introduction
2 Amide bioisosteric replacement in lead compounds optimization
2.1 Increasing the target potency and selectivity
2.2 Improving the drug-likeness of the lead compounds
2.3 Developing new structures to expand or break through the patents
2.4 Decreasing the difficulty of the synthesis of the compounds
3 Conclusion