2. Academic Validation
  3. Innovative medicinal chemistry strategies for enhancing drug solubility

Innovative medicinal chemistry strategies for enhancing drug solubility

  • Eur J Med Chem. 2024 Dec 5:279:116842. doi: 10.1016/j.ejmech.2024.116842.
Zhangxu He 1,  Weiguang Yang 2,  Feifei Yang 1,  Jingyu Zhang 3,  Liying Ma 4
Affiliations

Affiliations

  • 1 Pharmacy College, Henan University of Chinese Medicine, 450046, Zhengzhou, China.
  • 2 Children's Hospital Affiliated of Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Henan, Zhengzhou, 450000, China.
  • 3 Pharmacy College, Henan University of Chinese Medicine, 450046, Zhengzhou, China. Electronic address: [email protected].
  • 4 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China; China Meheco Topfond Pharmaceutical Co., Zhumadian, 463000, China. Electronic address: [email protected].
PMID: 39260319 DOI: 10.1016/j.ejmech.2024.116842
Abstract

Drug candidates with poor solubility have been recognized as the cause of many drug development failures, owing to the fact that low solubility is unfavorable for physicochemical, pharmacokinetic (PK) and pharmacodynamic (PD) properties. Given the imperative role of solubility during drug development, we herein summarize various strategies for solubility optimizations from a medicinal chemistry perspective, including introduction of polar group, salt formation, structural simplification, disruption of molecular planarity and symmetry, optimizations on the solvent exposed region as well as prodrug design. In addition, methods for solubility assessment and prediction are reviewed. Besides, we have deeply discussed the strategies for solubility improvement. This paper is expected to be beneficial for the development of drug-like molecules with good solubility.

Keywords

Medicinal chemistry; Optimizations; Solubility.

Figures
Products