文献类型：期刊文献

英文题名：Chemical Structure-Related Drug-Like Criteria of Global Approved Drugs

作者：Mao, Fei[1];Ni, Wei[1];Xu, Xiang[1];Wang, Hui[1];Wang, Jing[1];Ji, Min[1];Li, Jian[1]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Mei Long Rd, Shanghai 200237, Peoples R China

年份：2016

卷号：21

期号：1

外文期刊名：MOLECULES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000369486800049)】；

基金：Financial support of this research provided by the National Natural Science Foundation of China (Grants 21222211, 91313303), the Program for New Century Excellent Talents in University (Grant NCET-12-0853), "Shu Guang" project supported by Shanghai Municipal Education Commission, Shanghai Education Development Foundation (Grant 14SG28) and the Fundamental Research Funds for the Central Universities (Grant 22A201514054) is gratefully acknowledged.

语种：英文

外文关键词：drug-like property; chemical structure-related criteria; ring system; functional group; the heavy atoms proportion; drug design

摘要：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.