The chemical structure of a drug determines its physicochemical properties, 
further determines its ADME/Tox properties, and ultimately affects its 
pharmacological activity. Medicinal chemists can regulate the pharmacological 
activity of drug molecules by modifying their structure. Ring systems and 
functional groups are important components of a drug. The proportion of 
non-hydrocarbon atoms among non-hydrogen atoms reflects the heavy atoms 
proportion of a drug. The three factors have considerable potential for the 
assessment of the drug-like properties of organic molecules. However, to the 
best of our knowledge, there have been no studies to systematically analyze the 
simultaneous effects of the number of aromatic and non-aromatic rings, the 
number of some special functional groups and the proportion of heavy atoms on 
the drug-like properties of an organic molecule. To this end, the numbers of 
aromatic and non-aromatic rings, the numbers of some special functional groups 
and the heavy atoms proportion of 6891 global approved small drugs have been 
comprehensively analyzed. We first uncovered three important structure-related 
criteria closely related to drug-likeness, namely: (1) the best numbers of 
aromatic and non-aromatic rings are 2 and 1, respectively; (2) the best 
functional groups of candidate drugs are usually -OH, -COOR and -COOH in turn, 
but not -CONHOH, -SH, -CHO and -SO3H. In addition, the -F functional group is 
beneficial to CNS drugs, and -NH2 functional group is beneficial to 
anti-infective drugs and anti-cancer drugs; (3) the best R value intervals of 
candidate drugs are in the range of 0.05-0.50 (preferably 0.10-0.35), and R 
value of the candidate CNS drugs should be as small as possible in this 
interval. We envision that the three chemical structure-related criteria may be 
applicable in a prospective manner for the identification of novel candidate 
drugs and will provide a theoretical foundation for designing new chemical 
entities with good drug-like properties.