Applications of oxetanes in drug discovery and medicinal chemistry

被引：16

作者：

Huang, Guang ^{[1
]}

Hucek, Devon ^{[1
]}

Cierpicki, Tomasz ^{[1
]}

Grembecka, Jolanta ^{[1
]}

机构：

[1] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2023年 / 261卷

关键词：

Oxetanes; Drug design; Drug discovery; Kinase; Enzyme; Inhibitors; BRUTONS TYROSINE KINASE; FATTY-ACID SYNTHASE; HOMOLOG; EZH2; SELECTIVE INHIBITOR; SERINE SYNTHESIS; RATIONAL DESIGN; C-THETA; POTENT; PROTEIN; CANCER;

D O I：

10.1016/j.ejmech.2023.115802

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The compact and versatile oxetane motifs have gained significant attention in drug discovery and medicinal chemistry campaigns. This review presents an overview of the diverse applications of oxetanes in clinical and preclinical drug candidates targeting various human diseases, including cancer, viral infections, autoimmune disorders, neurodegenerative conditions, metabolic disorders, and others. Special attention is given to biologically active oxetane-containing compounds and their disease-related targets, such as kinases, epigenetic and nonepigenetic enzymes, and receptors. The review also details the effect of the oxetane motif on important properties, including aqueous solubility, lipophilicity, pKa, P-glycoprotein (P-gp) efflux, metabolic stability, conformational preferences, toxicity profiles (e.g., cytochrome P450 (CYP) suppression and human ether-a-go-go related gene (hERG) inhibition), pharmacokinetic (PK) properties, potency, and target selectivity. We anticipate that this work will provide valuable insights that can drive future discoveries of novel bioactive oxetanecontaining small molecules, enabling their effective application in combating a wide range of human diseases.

引用

页数：32

共 160 条

[1] An axonal stress response pathway: degenerative and regenerative signaling by DLK [J].