Current status of N-, O-, S-heterocycles as potential alkaline phosphatase inhibitors: a medicinal chemistry overview

Abstract

Heterocycles are a class of compounds that have been found to be potent inhibitors of alkaline phosphatase (AP), an enzyme that plays a critical role in various physiological processes such as bone metabolism, cell growth and differentiation, and has been linked to several diseases such as cancer and osteoporosis. AP is a widely distributed enzyme, and its inhibition has been considered as a therapeutic strategy for the treatment of these diseases. Heterocyclic compounds have been found to inhibit AP by binding to the active site of the enzyme, thereby inhibiting its activity. Heterocyclic compounds such as imidazoles, pyrazoles, and pyridines have been found to be potent AP inhibitors and have been studied as potential therapeutics for the treatment of cancer, osteoporosis, and other diseases. However, the development of more potent and selective inhibitors that can be used as therapeutics for the treatment of various diseases is an ongoing area of research. Additionally, the study of the mechanism of action of heterocyclic AP inhibitors is an ongoing area of research, which could lead to the identification of new targets and new therapeutic strategies. The enzyme known as AP has various physiological functions and is present in multiple tissues and organs throughout the body. This article presents an overview of the different types of AP isoforms, their distribution, and physiological roles. It also discusses the structure and mechanism of AP, including the hydrolysis of phosphate groups. Furthermore, the importance of AP as a clinical marker for liver disease, bone disorders, and cancer is emphasized, as well as its use in the diagnosis of rare inherited disorders such as hypophosphatasia. The potential therapeutic applications of AP inhibitors for different diseases are also explored. The objective of this literature review is to examine the function of alkaline phosphatase in various physiological conditions and diseases, as well as analyze the structure–activity relationships of recently reported inhibitors. The present review summarizes the structure–activity relationship (SAR) of various heterocyclic compounds as AP inhibitors. The SAR studies of these compounds have revealed that the presence of a heterocyclic ring, particularly a pyridine, pyrimidine, or pyrazole ring, in the molecule is essential for inhibitory activity. Additionally, the substitution pattern and stereochemistry of the heterocyclic ring also play a crucial role in determining the potency of the inhibitor.