Heterocyclic Tyrosine Kinase Inhibitors: Structural Insights and Medicinal Chemistry Strategies in Cancer, Immune-Mediated Disorders and Myeloproliferative Neoplasms

Abstract

Tyrosine kinases (TRs) regulate cellular signaling pathways involved in cell growth changes in cell type, survival, formation of new blood vessels, and responses from the immune system. When tyrosine kinases on the surface or inside the cells work, they play a significant role in making cancer problems with the immune system and inflammation and also in making too many blood cells. The creation of medicines that block tyrosine kinases has shown how important special ring-shaped molecules are for making these medicines work well, be specific, and have good effects in the body. This review provides a look at the chemistry side of medicines that block tyrosine kinases and focuses on how their chemical shapes, ring structures, the kinases they target, and the ways they are used in treatment are connected. The review talks about gefitinib, which is based on a quinazoline ring and targets EGFR, Lapatinib, which is made from a quinoline ring and targets EGFR and HER2, Imatinib, which has a part and targets BCR–ABL, KIT, and PDGFR, Ponatinib, which has an imidazopyridazine part and was made to work against BCR–ABL, especially the T315I mutation, and Dasatinib, which has a thiazole part and works against BCR–ABL and SRC-family kinases. In diseases where the immune system is not working correctly or there is much inflammation, the review talks about Tofacitinib, which is a heterocyclic JAK inhibitor, and Ibrutinib and Zanubrutinib, which are covalent BTK inhibitors based on a pyrazolopyrimidine ring. The way these medicines work with the kinases and the shapes they have are explained. The way blocking kinases helps in neoplasms is shown by Pacritinib, which blocks many kinases and targets JAK2 and related paths and Ruxolitinib, which blocks JAK1 and JAK2. Special attention is given to the variety of ring structures how they work with the ATP molecule how they find the hinge area how they block the kinase in an temporary way how specific they are and how the shapes of the medicines relate to their effects. Overall, the medicines described show how changing the ring parts and other parts of the molecules has led to medicines that target specific problems, in cancer, immune diseases, and myeloproliferative neoplasms.