Computational Structural Chemistry, Merck & Co., Inc., West Point, Pennsylvania 19486, United States.
Discovery Chemistry, Merck & Co., Inc., West Point, Pennsylvania 19486, United States.
J Med Chem. 2020 Jul 23;63(14):7447-7457. doi: 10.1021/acs.jmedchem.9b01932. Epub 2020 Feb 24.
The term "sulfa allergy", originally coined for the sulfonamide antibiotics, has become associated with any drugs that contain a sulfonamide moiety. This raises a question: should medicinal chemists avoid making sulfonamide-containing compounds in drug discovery programs? The negative perception of sulfonamides is not supported by any systematic study or data analysis. To address this gap, an analysis of postmarketing reports of cutaneous AEs for drugs with and without a sulfonamide group was conducted. The analysis revealed no evidence of association between the presence of a sulfonamide moiety and a high reporting rate of cutaneous AEs and indicated that the risk of such AEs was associated with the presence of certain structural alerts and higher daily doses. These results strongly suggest that sulfonamide-containing compounds are not at a higher risk of presenting with a cutaneous adverse drug reaction compared with non-sulfonamides and that medicinal chemists should not avoid use of the sulfonamide group.
“磺胺过敏”一词最初是为磺胺类抗生素创造的，现在已经与任何含有磺胺部分的药物联系在一起。这就提出了一个问题：药物发现计划中的药物化学家是否应该避免制造含磺胺的化合物？没有任何系统研究或数据分析支持对磺胺类药物的负面看法。为了解决这一差距，对具有和不具有磺胺基团的药物的上市后皮肤不良反应报告进行了分析。分析结果表明，磺胺部分的存在与皮肤不良反应高报告率之间没有关联，并且表明此类不良反应的风险与某些结构警示和更高的每日剂量有关。这些结果强烈表明，与非磺胺类药物相比，含磺胺的化合物发生皮肤不良反应的风险并不更高，药物化学家不应该避免使用磺胺基团。
