Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
SAR QSAR Environ Res. 2009 Oct;20(7-8):611-55. doi: 10.1080/10629360903438313.
Acid-base ionization constant (pK(a)) values have considerable influence on the physicochemical and pharmacokinetic properties of therapeutic substances. A set of 907 drugs was examined to determine the proportion of drugs that contain an ionizable group and the distribution of their pK(a) values. Using this contemporary set of compounds it was found that 64% of these compounds contained an ionizable group. Within this group of ionizable compounds, 34% contained a single basic group while only 20% contained a single acidic functional group. The single acid and single base containing substances were investigated further to examine the distributions of their pK(a) values. These data are discussed and analyzed with a focus on the entire set as well as central nervous system, non-central nervous system and oral drugs. The findings from this research will prompt pharmaceutical companies to assess the constitution of their screening libraries, such that focus is placed on the proportion of ionizable substances, the ratio of acids to bases and the distribution of pK(a) values.
酸基离解常数 (pK(a)) 值对治疗物质的物理化学和药代动力学特性有很大影响。本研究考察了一组 907 种药物，以确定含可离解基团的药物比例及其 pK(a) 值的分布。使用这组当代化合物，发现 64%的化合物含有可离解基团。在这组可离解化合物中，34%含有一个单一的碱性基团，而只有 20%含有一个单一的酸性官能团。对含有单一酸和单一碱的物质进行了进一步研究，以检查其 pK(a) 值的分布。本文对这些数据进行了讨论和分析，重点是整个数据集以及中枢神经系统、非中枢神经系统和口服药物。这项研究的结果将促使制药公司评估其筛选库的组成，以便将重点放在可离解物质的比例、酸与碱的比例以及 pK(a) 值的分布上。
