Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, United States.
Discovery Research, AbbVie Inc., 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
J Med Chem. 2024 Jul 25;67(14):11622-11655. doi: 10.1021/acs.jmedchem.4c01122. Epub 2024 Jul 12.
This Perspective is a continuation of our analysis of U.S. FDA-approved small-molecule drugs (1938-2012) containing nitrogen heterocycles. In this study we report drug structure and property analyses of 321 unique new small-molecule drugs approved from January 2013 to December 2023 as well as information about frequency of important heteroatoms such as sulfur and fluorine and key small nitrogen substituents (CN and NO). The most notable change is an incredible increase in drugs containing at least one nitrogen heterocycle─82%, compared to 59% from preceding decades─as well as a significant increase in the number of nitrogen heterocycles per drug. Pyridine has claimed the #1 high-frequency nitrogen heterocycle occurrence spot from piperidine (#2), with pyrimidine (#5), pyrazole (#6), and morpholine (#9) being the big top 10 climbers. Also notable is high number of fused nitrogen heterocycles, apparently driven largely by newly approved cancer drugs.
这篇观点文章是我们对美国食品药品监督管理局（FDA）批准的含氮杂环的小分子药物（1938-2012 年）分析的延续。在这项研究中，我们报告了 2013 年 1 月至 2023 年 12 月期间批准的 321 种独特新型小分子药物的药物结构和性质分析，以及有关重要杂原子（如硫和氟）和关键小氮取代基（CN 和 NO）的频率信息。最显著的变化是，含有至少一个氮杂环的药物数量惊人地增加了——82%，而前几十年的这一比例为 59%——而且每种药物的氮杂环数量也显著增加。吡啶取代了哌啶（#2），成为出现频率最高的氮杂环（#1），嘧啶（#5）、吡唑（#6）和吗啉（#9）则是前 10 名中上升最快的。值得注意的是，稠合氮杂环的数量也很多，显然主要是受新批准的癌症药物推动。
