Objective:In the early stages of drug research and development

the enantiomers were usually treated as a single optical pure compound due to the limitations of knowledge and conditions. With the development of chiral separation technology and the increasing awareness of chiral drugs

the effects of chirality on pharmacological activity

toxicity

and metabolic properties of drugs have been gradually regarded. Several adverse reactions due to the chirality

such as the ‘thalidomide event’ in Europe

have led drug developers to pay more attention to chiral factors in drugs. Axial chirality is a special form of chirality

where the covalent bond cannot rotate freely due to steric hindrance or electronic effects. Axial chirality also has extensive effects on pharmacological activity and metabolic properties of compounds

but it is usually neglected since the molecule does not possess a stereogenic center. Drug research and development is a lengthy and expensive process. Therefore

axis chirality should be paid enough attention in the early stage to minimize the risks in advanced development and clinical trials. For chiral drugs

FDA has issued relevant documents to guide the research and development since 1992.However

there is no specific provision for the development of axial-chiral drugs. In this paper

the progress of axis-chiral drugs research is reviewed and discussed from four aspects:generation

configuration judgment

axial chirality-activity relationship

and development trend of axis-chiral drugs. The importance of axis-chirality in the process of drug research and development is also discussed

which is of reference value for the research and development of axis-chiral drugs.